KR101202727B1 - 위장병 치료 방법 및 위장병 치료용 조성물 - Google Patents

위장병 치료 방법 및 위장병 치료용 조성물 Download PDF

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KR101202727B1
KR101202727B1 KR1020067020883A KR20067020883A KR101202727B1 KR 101202727 B1 KR101202727 B1 KR 101202727B1 KR 1020067020883 A KR1020067020883 A KR 1020067020883A KR 20067020883 A KR20067020883 A KR 20067020883A KR 101202727 B1 KR101202727 B1 KR 101202727B1
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xaa
peptide
tyr
peptides
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마크 지. 커리
살리나 마하잔-미클로스
안겔리카 프레첸
리징 선
지. 토드 밀른
티아 노만
캐롤라인 쿠르츠
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아이언우드 파마슈티컬스, 인코포레이티드
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Abstract

본 발명은 IBS, 기타 위장병 및 증상(예, 위장 운동 장애, 기능성 위장병, 위식도 역류성 질환(gastroesophageal reflux disease)(GERD), 십이지장-위 역류(duodenogastric reflux), 크론씨 병, 궤양성 직장염(ulcerative colitis), 염증성 장 질환, 기능성 속쓰림, 소화불량(기능성 소화불량 및 비궤양성 소화불량 포함), 위부전마비(gastroparesis), 만성 가성 장 폐쇄(chronic intestinal pseudo-obstruction)(또는, 만성 가성 대장폐쇄(colonic pseudo-obstruction)), 및 변비 관련 질환 및 증상, 예, 무통증 아편제(opiate pain killer)의 사용과 관련된 변비, 수술후 변비(수술후 장 폐색), 및 신경성 질환 뿐만 아니라 구아닐레이트 사이클라제 C(GC-C) 수용체(guanylate cyclase 수용체)를 활성화시키는 펩티드 및 그외 제제를 이용한 그외 증상 및 질환을 치료하기 위한 조성물 및 방법에 관한 것이다.
위장병, 펩티드

Description

위장병 치료 방법 및 위장병 치료용 조성물{METHODS AND COMPOSITIONS FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS}
본 출원은 제 35USC§119(e)의 규정에 따라 2003년 1월 28일자 미국 가출원 제 60/443,098호, 2003년 5월 15일자 제 60/471,288 및 2003년 11월 12일자 제 60/519,460호에 대한 우선권을 주장하는, 2004년 1월 28일자 제 10/766,735의 일부 계속 출원인, 2004년 3월 9일자 제 10/796,719호의 일부 계속 출원인, 2004년 5월 14일자 제 10/845,895호의 일부 계속 출원인, 2004년 7월 27일자 제 10/899,806호의 일부 계속 출원인, 2005년 2월 8일자 미국 특허 출원번호 제 11/054,071호의 일부 계속 출원이다. 이들 출원들의 내용은 원용에 의해 본 발명에 포함된다.
본 발명은 위장병, 비만, 울혈성 심부전증(congestive heart failure) 및 양성 전립선 비대증(benign prostatic hyperplasia)을 포함한 여러가지 질병의 치료 방법 및 치료용 조성물에 관한 것이다.
과민성 대장 증후군(irritable bowel syndrome (IBS))은 미국에서만도 2 천만명 내지 6 천만명에 이르는 인구에서 나타나는 일반적인 만성 장 질환이다(Lehman Brothers, Global Healthcare-Irritable bowel syndrome industry update, September 1999). IBS는 소화기 전문의에 의해 진단되는(검사한 환자들중 28%) 가장 흔한 질병이며, 일차 의료 의사에게 진료받는 진료자의 12%를 차지한다(Camilleri 2001, Gastroenterology 120: 652-668). 미국에서는, 직접적인 건강 관리 비용과 장기 결근으로 인한 간접적인 비용을 통틀어, IBS로 인한 경제적 파장이 매년 250억 달러에 달하는 것으로 추산하고 있다(Talley 1995, Gastroenterology 109: 1736-1741). IBS 환자는 3배 높은 결근율을 보이며 삶의 질이 감소되는 것으로 보고되고 있다.
IBS 환자는 사교모임에 참가하거나, 고용상태를 유지하거나 또는 단거리를 여행하는 것 조차도 할 수 없거나 마음내켜하지 않을 수 있다(Drossman 1993, Dig Dis Sci 38 :1569-1580). IBS를 치료하기 위한 처방 옵션이 거의 없기 때문에 상기 환자들의 상당한 의학적 요구들이 미충족되고 있다.
IBS 환자는 복부 통증과 교란성 배변 양상(disturbed bowel pattern)을 겪는다. IBS 환자는 주된 배변 습관을 기초로 3가지 하위군으로 분류된다: 변비-주증세(c-IBS), 설사-주증세(d-IBS) 또는 상기 두가지 증세가 번갈아 나타나는 군(a-IBS). c-IBS 형의 환자는 IBS 환자에 20-50%를 차지하는 것으로 추산되며, 종종 30%인 것으로 언급되고 있다. 유사한 성 비율을 갖는 나머지 두 하위군과는 달리, c-IBS는 여성에게서 일반적으로 나타난다(비율 3:1)(Talley et al. 1995, Am J Epidemiol 142: 76-83).
IBS의 진단 및 진단 기준은 임상 실무에 널리 적용되는 "Rome Criteria" (Drossman et al. 1999, Gut 45:Suppl II : 1-81)에 규정되어 있다. 그러나, 복합 증상은 해부학적 이상 또는 대사 변이로 설명되지 않는다. 이 경우 IBS는 GI 기능 장애로 분류되며, Rome criteria을 토대로 진단되며, 평가가 제한적이어서 기질적 질환(organic disease)은 제외된다(Ringel et al. 2001, Annu Rev Med 52 : 319-338). IBS는 3가지의 상호작용 기작들의 조합으로 발생되는 "생물심리학적(biopsychosocial)" 질환으로 간주된다: 장 운동 변이, 장 또는 결장의 통증 자극에 대한 민감성(내장 민감성) 증가 및 심리사회적 요소들(Camilleri 2001, Gastroenterology 120: 652-668). 최근, 염증 작용이 IBS의 병인이라는 증거가 점차 증가하고 있다. IBS 환자들 중 일부 소수에서 결장의 염증과 비만세포(mast cell)가 유의적으로 증가되고, 유도성 질소 산화물(NO)과 이의 합성효소(iNOS)가 증가되며, 염증성 사이토카인의 발현이 변이된 것으로 보고되고 있다(reviewed by Talley 2000, Medscape Coverageof DDW week).
개요
본 발명은 IBS, 기타 위장병 및 증상(예, 위장 운동 장애, 만성 가성 장 폐쇄(chronic intestinal pseudo-obstruction), 만성 가성 대장폐쇄(colonic pseudo-obstruction), 크론씨 병, 십이지장-위 역류(duodenogastric reflux), 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속 쓰림(functional heartburn), 위식도 역류성 질환(gastroesophageal reflux disease)(GERD), 위부전마비(gastroparesis), 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염(ulcerative colitis), 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제(opiate pain killer)의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비)을 치료하기 위한 조성물 및 방법에 관한 것이다. 상기 조성물은 구아닐레이트 사이클라제 C(GC-C) 수용체(guanylate cyclase 수용체)를 활성화시키는 펩티드를 특징으로 한다.
또한, 본 발명은 비만, 울혈성 심부전증 및 양성 전립선 비대증(BPH)를 치료하기 위한 조성물 및 방법에 관한 것이다.
특정 이론에 결부됨이 없이, 상기 펩티드는 위장 운동성을 증가시킬 수 있으므로 IBS 및 기타 위장병에 유용하다.
특정 이론에 결부됨이 없이, 상기 펩티드는 염증을 감소시킬 수 있으므로 IBS 및 기타 위장병에 유용하다.
특정 이론에 결부됨이 없이, 상기 펩티드는 위장 통증 또는 내장 통증(visceral pain)을 감소시킬 수 있으므로 IBS 및 기타 위장병에 유용하다.
본 발명은 구아닐레이트 사이클라제 C(GC-C) 수용체를 활성화시킬 수 있는 특정 펩티드를 포함하는 약학적 조성물에 관한 것이다. 또한 본 발명은, 본 발명의 펩티드 또는 GC-C 작용제 및 본 발명에 기재된 제제를 비제한적으로 포함하는 하나 이상의 추가적인 치료제를 포함하는 약학적 조성물에 관한 것이다. 그외 제제도 본 발명의 펩티드와 (동시에 또는 순차적으로) 함께 투여할 수 있다. 또한 이들은 본 발명의 펩티드에 연결시켜, 치료학적 접착제를 제조할 수 있다.
본 발명은 GC-C 수용체의 부분 작용제 또는 완전 작용제로서 작용하는 펩티드를 투여함으로써 다양한 위장병을 치료하는 방법은 포함한다. 상기 펩티드는 3개의 이황화 결합을 형성할 수 있는 최소 6개 이상의 시스테인을 포함한다. 특정 예에 있어서, 상기 이황화 결합은 기타 공유 교차-연결로 대체되며, 일부의 경우 대안적인 공유 교차-연결을 제공하기 위해 상기 시스테인은 다른 잔기로 교체된다. 또한, 상기 펩티드는 하나 이상의 트립신 절단 부위 또는 키모트립신 절단 부위 및/또는 카르복시 말단의 진통성 펩티드 또는 작은 분자, 예컨대 AspPhe 또는 그외 진통성 펩티드를 포함할 수 있다. 펩티드내에 존재하는 경우, 진통성 펩티드 또는 작은 분자는 진통성 펩티드 또는 작은 분자를 분리시키는 키모트립신 또는 트립신 절단 부위의 하위에 둘 수 있다. 본 발명의 펩티드 및 방법은 또한 위장병을 포함한, 다양한 질환과 관련된 통증 및 염증을 치료하는데 유용하다. 특정 펩티드는 절단시 펩티드가 비활성화되도록 위치된 기능성 키모트립신 또는 트립신 절단 부위를 포함하다. 기능성 절단 부위를 가진 특정 펩티드는, 소화관에서 절단되고 점차 불활성화되며, 이는 어떠한 조건에서 바람직하다. 특정 펩티드에서, 기능성 키모트립신 부위가 변이되면 생체내에서의 펩티드 안정성이 증가한다.
본 발명은 GC-C 수용체의 작용제로서 작용하는 펩티드 또는 작은 분자를 (비경구로 또는 경구로) 투여함에 의한, 울혈성 심부전증 및 양성 전립선 비대증과 같은 그외 질환을 치료하는 방법을 포함한다. 이러한 제제는 나트륨 이뇨 펩티드(natriuretic peptide))(예, 심방성 나트륨 이뇨 펩타이(atrial natriuretic peptide), 뇌성 나트륨 이뇨 펩티드(brain natriuretic peptide), C형 나트륨 이뇨 펩티드), 이뇨제 또는 안지오텐신 전환 효소 저해제와 함께 조합(병용)하여 사용할 수 있다.
본 발명은 장 운동을 증가시키기 위한 방법 및 조성물에 관한 것이다. 장 운동에는 음식물을 소화시키는 동안 위장관을 통하여 이동시키기 위한 위, 장, 결장 및 직장의 자발적인 등위성 불일치(coordinated dissention) 및 수축이 수반된다.
특정 예에 있어서, 상기 펩티드는 카르복시 말단에 1 또는 2 개 이상의 인접한 음전하성 아미노산(예, Asp 또는 Glu)이나, 또는 1 또는 2 개 이상의 인접한 양전하성 잔기(예, Lys 또는 Arg), 또는 1 또는 2 개 이상의 인접한 양전하성 또는 음전하성 아미노산중 어느 하나를 포함한다. 이러한 예에서, 카르복시 말단에 플랜킹(flanking) 아미노산은 모두 양전하를 띄거나 또는 음전하를 띈다. 다른 예에서, 카르복시 말단의 하전된 아미노산은 Leu의 상위에 위치한다. 예를들어, 아래 아미노산 서열을 상기 펩티드의 카르복시 말단에 부가할 수 있다: Asp; Asp Lys; Lys Lys Lys Lys Lys Lys; Asp Lys Lys Lys Lys Lys Lys; Leu Lys Lys; 및 Leu Asp. 또한 카르복시 말단에 Leu를 단순히 첨가 가능하다.
제 1 측면으로, 본 발명은 아래 아미노산 서열(I)을 필수적으로 포함하는, 으로 구성된 또는 필수적으로 구성되는 펩티드에 관한 것이다:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21(서열번호 1)
일부 예에서, 상기 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5는 Asn Ser Ser Asn Tyr 이거나 또는 생략되거나, 또는 Xaa1 Xaa2 Xaa3 Xaa4는 생략된다.
특정 예에서, 상기 Xaa8, Xaa9, Xaa12, Xaa14, Xaa16, Xaa17 및 Xaa19는 임의의 아미노산일 수 있다. 특정 예에서, 상기 Xaa8, Xaa9, Xaa12, Xaa14, Xaa16, Xaa17 및 Xaa19는 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체일 수 있다.
특정 예에서, 상기 펩티드는 E.coli ST 펩티드의 서열을 포함하지 않는다. 다른 예로, 상기 펩티드는 하기 표 1의 모든 펩티드의 서열을 포함하지 않는다.
특정 예로, 상기 Xaa5는 Asn, Trp, Tyr, Asp 또는 Phe이다. 다른 예로서, 상기 Xaa5는 Thr 또는 Ile일 수 있다. 다른 예로서, 상기 Xaa5는 Tyr, Asp 또는 Trp이다. 일부 예로서, 상기 Xaa5는 Asn, Trp, Tyr, Asp, Ile, Thr 또는 Phe이다. 특정 예로, 상기 Xaa5는 Asn이다.
일부 예들에서, 상기 Xaa8은 Glu, Asp, Gln, Gly 또는 Pro이다. 다른 예로서, 상기 Xaa8은 Glu이다. 다른 예로서, 상기 Xaa8은 Glu 또는 Asp이다. 다른 예로서, 상기 Xaa8은 Asn, Glu 또는 Asp이다. 다른 예로서, 상기 Xaa8은 Glu, His, Lys, Gln, Asn 또는 Asp이다. 다른 예로서, 상기 Xaa8은 Glu, His, Gln, Asn 또는 Asp이다. 다른 예로서, 상기 Xaa8은 Glu, Asn, His, Gln, Lys, Asp 또는 Ser이다. 또다른 예로서, 상기 Xaa8은 Pro이다. 특정 예로서, 상기 Xaa8은 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다.
일부 예로서, 상기 Xaa9는 Leu, Ile, Val, Ala, Lys, Arg, Trp, Tyr 또는 Phe이다. 일부 예로서, 상기 Xaa9는 Leu, Ile, Val, Lys, Arg, Trp, Tyr 또는 Phe이다. 다른 예로서, 상기 Xaa9는 Leu, Ile, Val, Trp, Tyr 또는 Phe이다. 다른 예로서, 상기 Xaa9는 Leu, Ile 또는 Val이다. 다른 예로서, 상기 Xaa9는 Trp, Tyr 또는 Phe이다. 다른 예로서, 상기 Xaa9는 Leu, Ile, Lys, Arg, Trp, Tyr 또는 Phe이다. 다른 예로서, 상기 Xaa9는 Leu, Val, Ile 또는 Met이다. 다른 예로서, 상기 Xaa9는 Leu 또는 Phe이다. 다른 예로서, 상기 Xaa9는 Leu, Phe 또는 Tyr이다. 다른 예로서, 상기 Xaa9는 Tyr, Phe 또는 His이다. 다른 예로서, 상기 Xaa9는 Phe, His, Trp 또는 Tyr이다. 특정 예로서, 상기 Xaa9는 Leu가 아니다. 다른 예로서, 상기 Xaa9는 Tyr이다. 다른 예로서, 상기 Xaa9는 임의의 천연 또는 비천연성 방향족 아미노산이거나 또는 아미노산 유사체이다. 특정 예로서, 상기 Xaa9는 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다.
특정 예들에서, 상기 Xaa12는 Asn, Tyr, Asp 또는 Ala이다. 다른 예에서, 상기 Xaa12는 Asn이다. 다른 예에서, 상기 Xaa12는 Asn, Met, Arg, Lys, His 또는 Gln이다. 다른 예에서, 상기 Xaa12는 Asn, Lys, His 또는 Gln이다. 다른 예에서, 상기 Xaa12는 Asn, Asp, Glu 또는 Gln이다. 다른 예에서, 상기 Xaa12는 Asn, Thr, Ser, Arg, Lys, Glu 또는 His이다. 다른 예에서, 상기 Xaa12는 Asn, Ser 또는 His이다. 특정 예에서, 상기 Xaa12는 또ㄴ일부 실시예들에서, 상기 Xaa13은 Ala, Pro 또는 Gly이며, 다른 실시예들에서는 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다.
특정 예에서, 상기 Xaa13은 Ala, Pro 또는 Gly이다. 다른 예에서, 상기 Xaa13은 Pro 또는 Gly이다. 다른 예에서, 상기 Xaa13은 Pro이고, 또다른 예에서, 상기 Xaa13은 Gly이다.
특정 예에서, 상기 Xaa14는 Ala, Leu, Ser, Gly, Val, Glu, Gln, Ile, Leu, Thr, Lys, Arg 또는 Asp이다. 다른 예에서, 상기 Xaa14는 Ala 또는 Gly이다. 다른 예에서, 상기 Xaa14는 Val 또는 Ala이다. 다른 예에서, 상기 Xaa14는 Ala 또는 Thr이다. 다른 예에서, 상기 Xaa14는 Ala이다. 다른 예에서, 상기 Xaa14는 Val, Gln, Asn, Glu, Asp, Thr 또는 Ala이다. 다른 예에서, 상기 Xaa14는 Gly, Cys 또는 Ser이다. 또다른 예에서, 상기 Xaa14는 Thr이다. 특정 예에서, 상기 Xaa14는 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다.
특정 예들에서, 상기 Xaa16은 Thr, Ala, Asn, Lys, Arg, Trp, Gly 또는 Val이다. 다른 예들에서, 상기 Xaa16은 Thr, Ala, Asn, Lys, Arg 또는 Trp이다. 다른 예들에서, 상기 Xaa16은 Thr, Ala, Lys, Arg 또는 Trp이다. 특정 예들에서, 상기 Xaa16은 Thr, Ala 또는 Trp이다. 다른 예들에서, 상기 Xaa16은 Thr이다. 특정 예들에서, 상기 Xaa16은 Trp, Tyr 또는 Phe이다. 특정 예들에서, 상기 Xaa16은 Thr 또는 Ala이다. 특정 예들에서, 상기 Xaa16은 Val이다. 특정 예들에서, 상기 Xaa16은 Gly이다. 다른 예들에서, 상기 Xaa16은 Thr, Ser, Met 또는 Val이다. 다른 예들에서, 상기 Xaa16은 Val, Ala 또는 Thr이다. 다른 예들에서, 상기 Xaa16은 Ile, Val, Lys, Asn, Glu, Asp 또는 Thr이다. 특정 예들에서, 상기 Xaa16은 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다. 특정 예들에서, 상기 Xaa16은 임의의 천연 또는 비천연성 비방향족 아미노산이거나 또는 아미노산 유사체이다.
특정 예에서, 상기 Xaa17은 Gly, Pro 또는 Ala이다. 특정 예에서, 상기 Xaa17은 Gly이다. 특정 예에서, 상기 Xaa17은 Ala이다. 다른 예에서, 상기 Xaa17은 Gly 또는 Ala이다. 다른 예에서, 상기 Xaa17은 Gly, Asn, Ser 또는 Ala이다. 다른 예에서, 상기 Xaa17은 Asn, Glu, Asp, Thr, Ala, Ser 또는 Gly이다. 다른 예에서, 상기 Xaa17은 Asp, Ala, Ser 또는 Gly이다. 특정 예에서, 상기 Xaa17은 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다.
특정 예에서, 상기 Xaa19는 Trp, Tyr, Phe, Asn, Ile, Val, His, Leu 또는 Arg이다. 특정 예에서, 상기 Xaa19는 Trp, Tyr, Asn 또는 Leu이다. 특정 예에서, 상기 Xaa19는 Trp, Tyr 또는 Phe이다. 다른 예에서, 상기 Xaa19는 Tyr, Phe 또는 His이다. 다른 예에서, 상기 Xaa19는 Tyr 또는 Trp이다. 다른 예에서, 상기 Xaa19는 Tyr이다. 특정 예에서, 상기 Xaa19는 Leu, Ile 또는 Val이다. 특정 예에서, 상기 Xaa19는 His이다. 특정 예에서, 상기 Xaa19는 Trp, Tyr, Phe, Asn, Ile, Val, His 또는 Leu이다. 특정 예에서, 상기 Xaa19는 Trp, Tyr, Phe 또는 Leu이다. 특정 예에서, 상기 Xaa19는 Tyr 또는 Leu이다. 특정 예에서, 상기 Xaa19는 Lys 또는 Arg이다. 특정 예에서, 상기 Xaa19는 Pro, Arg, Lys, Asp 또는 Glu이외의 임의의 다른 아미노산이다. 특정 예에서, 상기 Xaa19는 Pro 이외의 임의의 아미노산이다. 특정 예에서, 상기 Xaa19는 임의의 천연 또는 비천연 아미노산이거나 또는 아미노산 유사체이다. 특정 예에서, 상기 Xaa19는 생략된다.
특정 예에서, 상기 Xaa20은 Asp 또는 Asn이다. 특정 예에서, Xaa20 Xaa21은 AspPhe이거나 또는 생략되며, 또는 상기 Xaa20은 Asn 또는 Glu이고 Xaa21은 생략되거나, 또는 상기 Xaa19 Xaa20 Xaa21는 생략된다.
특정 실시예에 있어서, 본 발명은 아미노산 서열 (II)를 포함하는 정제된 폴리펩티드에 관한 것이다:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21이며,
상기에서, Xaa1 Xaa2 Xaa3 Xaa4 Xaa5는 Asn Ser Ser Asn Tyr 또는 생략되며, 또는 Xaa1 Xaa2 Xaa3 Xaa4는 생략되고 Xaa5는 Asn이고;
상기 Xaa8은 Glu 또는 Asp이고;
상기 Xaa9는 Leu, Ile, Val, Trp, Tyr 또는 Phe이고;
상기 Xaa16은 Thr, Ala 또는 Trp이고;
상기 Xaa19는 Trp, Tyr, Phe 또는 Leu이거나, 또는 생략되며; 및
상기 Xaa20 Xaa21은 AspPhe이다.
여러가지 예들에서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21(II)(을 포함하는 정제된 폴리펩티드에 관한 것으로, Xaa9는 Leu, Ile 또는 Val이고 Xaa16은 Trp, Tyr 및 Phe이거나; Xaa9는 Trp, Tyr 또는 Phe이고 Xaa16은 Thr ㄸ또는 Ala이고; Xaa19는 Trp, Tyr, Phe이고 Xaa20 Xaa21은 AspPhe이고; Xaa1 Xaa2 Xaa3 Xaa4 는 생략되고 Xaa5는 Asn이며, 사기 펩티드는 Cys6 상위에 50, 40, 30 또는 25개 이하의 아미노산, 또는 5개 이하의 아미노산을 포함한다.
여러가지 바람직한 예들에서, 상기 펩티드는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys Cys Glu Xaa9 Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr Xaa20 Xaa21(II)(서열번호 2)를 포함하는 또는 으로 구성된 펩티드를 포함하며, 상기에서, Xaa9는 임의의 아미노산이고; Xaa9는 Leu 이외의 임의의 아미노산이고, Xaa9는 Phe, Trp 및 Tyr에서 선택되며; Xaa9는 임의의 그외 천연 또는 비천연성 방향족 아미노산으로부터 선택되며; Xaa9는 Tyr이고; Xaa9는 Phe이고; Xaa9는 Trp이고; Xaa1Xaa2Xaa3Xaa4Xaa5는 Asn Ser Ser Asn Tyr이고; Xaa1 Xaa2 Xaa3 Xaa4 및 Xaa5는 생략되고; Xaa1 Xaa2 Xaa3 및 Xaa4는 생략되고; Xaa1 Xaa2 및 Xaa3는 생략되고; Xaa1 및 Xaa2는 생략되고; Xaa1은 생략되고; Xaa20 Xaa21은 AspPhe이거나 생략되며, 또는 Xaa20은 Asn 또는 Glu이고 Xaa21은 생략되며, 또는 Xaa19 Xaa20 Xaa21는 생략되며; 상기 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 및 Tyr Xaa20 Xaa21은 생략된다. Xaa1 Xaa2 Xaa3 Xaa4 Xaa5는 생략되고/되거나 Xaa19 Xaa20 Xaa21이 생략된, 서열(I): Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys111 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21을 포함하는 펩티드의 경우에서, 상기 펩티드는 추가적인 카르복시 말단 또는 아미노 말단 아미노산이나 이들 모두를 여전히 포함할 수 있다. Xaa1 또는 Xaa21과 같은 하나 이상의 말단 아미노산이 생략된 펩티드의 경우, 상기 펩티드는 추가적인 카르복시 말단 또는 아미노 말단 아미노산이나 이들 모두를 여전히 포함할 수 있다.
특정 예에서, 펩티드는 Cys6과 Cys11 사이에, Cys7과 Cys15 사이에, 그리고 Cys10과 Cys18 사이에 이황화 결합을 포함한다. 다른 예로, 펩티드는 이황화 결합이 없는 환원된 펩티드이다. 또다른 예로, 펩티드는 Cys6과 Cys11 사이의 이황화 결합, Cys7과 Cys15 사이의 이황화 결합 및 Cys10과 Cys18 사이의 이황화 결합으로 이루어진 군으로부터 선택된 하나 이상의 이황화 결합을 가진다.
특정 예에서, 하나 이상의 아미노산은 비천연 아미노산, 또는 천연 또는 비천연 아미노산 유사체로 치환될 수 있다. 표준적인 20개 이상의 많은 아미노산들이 있다. 일부는 천연형이고, 나머지는 비천연형이다(예, Hunt, The Non-Protein Amino Acids: In Chemistry and Biochemistry of the Amino Acids, Barrett, Chapman and Hall, 1985). 예컨대, 방향족 아미노산은 3,4-디하이드록시-L-페닐알라닌, 3-요오도-L-티로신, 트리요오도티로닌, L-티록신, 페닐글리신(Phg) 또는 노르-티로신(norTyr)으로 치환될 수 있다. Phg, norTyr, 및 Phe 및 Tyr를 함유하는 그외 아미노산들은, 예컨대 할로겐, -CH3, -OH, -CH2NH3, -C(O)H, -CH2CH3, -CN, -CH2CH2CH3, -SH, 또는 다른 기로 치환될 수 있다. 임의의 아미노산의 D-형의 아미노산으로 치환될 수 있다.
비천연성 아미노산, 또는 천연 아미노산 유사체 및 비천연 아미노산 유사체에 있어서, 식I 및 식II의 펩티드에서의 다수개의 친화는 상기의 단독이거나 또는 상기의 조합 형태일 수 있다.
Xaa8은 감마-하이드록시-Glu 또는 감마-카르복시-Glu로 치환될 수 있다.
Xaa9는 L-알파-메틸펜닐알라닌과 같은 알파 치환된 아미노산이나, 또는 3-아미노-Tyr; Tyr(CH3); Tyr(P03(CH3)2); Tyr(SO3H); 베타-사이클로헥실-Ala; 베타-(1-사이클로펜테닐)-Ala; 베타-사이클로펜틸-Ala; 베타-사이클로프로필-Ala; 베타-퀴놀릴-Ala; 베타-(2-티아졸릴)-Ala; 베타-(트리아졸-1-일)-Ala; 베타-(2-피리딜)-Ala; 베타-(3-피리딜)-Ala; 아미노-Phe; 플루오로-Phe; 사이클로헥실-Gly; tBu-Gly; 베타-(3-벤조티에닐)-Ala; 베타-(2-티에닐)-Ala; 5-메틸-Trp; 및 4-메틸-Trp와 같은 유사체로 치환될 수 있다.
Xaa13은 하기 구조식을 가지는 N(알파)-C(알파) 환형 아미노산 유사체일 수 있다:
Figure 112006072578425-pct00001
상기에서, n = 0, 1, 2, 3이다.
또한, Xaa13은 호모프로(L-피페콜릭산); 하이드록시-Pro; 3,4-디하이드로-Pro; 4-플루오로-Pro; 또는 알파-메틸-Pro일 수 있다.
Xaa13이 Gly, Ala, Leu 또는 Val이면, Xaa14는 n이 0, 1, 2, 또는 3인
Figure 112006072578425-pct00002
일 수 있다.
또한, Xaa14는 알파-아미노 이소부티르산(aib), L/D-알파-에틸알라닌(L/D-이소발린), L/D-메틸발린 또는 L/D-알파-메틸루신과 같은 알파-치환된 또는 N-메틸화된 아미노산이거나, 또는 베타-플루오로-Ala과 같은 비천연성 아미노산일 수 있다.
Xaa17은 알파-아미노 이소부티르산(aib) 또는 L/D-알파-에탈알라닌(L/D-이소발린)일 수 있다.
비천연성 아미노산의 다른 예로 하기의 것들이 있다: 티로신의 비천연성 유사체; 글루타민의 비천연성 유사체; 페닐알라닌의 비천연성 유사체; 세린의 비천연성 유사체; 트레오닌의 비천연성 유사체; 알킬, 아릴, 아실, 아지도, 시아노, 할로, 하이드라진, 하이드라지드, 하이드록실, 알케닐, 알키닐, 에테르, 티올, 설포닐, 셀레노, 에스테르, 티오액시드, 보레이트, 보로네이트, 포스포, 포스포노, 포스핀, 헤테로사이클릭, 에논, 이민, 알데하이드, 하이드록실아민, 케토 또는 아미노 치환된 아미노산, 또는 이들의 모든 조합; 광활성화가 가능한 교차-링커를 가진 아미노산; 스핀-표지된 아미노산; 형광 아미노산; 신규 관능기를 가진 아미노산; 다른 분자와 공유 또는 비공유결합으로 상호작용하는 아미노산; 금속 결합성 아미노산; 금속-함유 아미노산; 방사능 아미노산; 광포착(photocaged) 및/또는 광이성질화(photoisomerizable) 아미노산; 비오틴 또는 비오틴 유사체 함유 아미노산; 당화 또는 탄수화물 변형된 아미노산; 케토 함유 아미노산; 폴리에틸렌 글리콜 또는 폴리에테르를 포함하는 아미노산; 헤비 원소로 치환된 아미노산(예, 중수소, 삼중 수소, 13C, 15N, 또는 180를 포함하는 아미노산); 화학적으로 절단가능한 아미노산 또는 광절단가능한 아미노산; 연장된 측쇄를 가진 아미노산; 독성 기를 포함하는 아미노산; 당 치환된 아미노산, 예컨대 당 치환된 세린 등; 탄소-연결된 당-함유 아미노산; 환원산화-활성(redox-active) 아미노산; 알파-하이드록시 함유 아미노산; 아미노 티오산 함유 아미노산; α,α 이중치환된 아미노산; β-아미노산; 프롤린을 제외한 환형 아미노산; O-메탈-L-티로신; L-3-(2-나프틸)알라닌; 3-메탈-페닐알라닌; p-아세틸-L-페닐알라닌; O-4-알릴-L-티로신; 4-프로필-L-티로신; 트리-O-아세틸-GlcNAcβ-세린; L-도파; 플루오린화된 페닐알라닌; 이소프로필-L-페닐알라닌; p-아지도-L-페닐알라닌; p-아실-L-페닐알라닌; p-벤조일-L-페닐알라닌; L-포스포세린; 포스포노세린; 포스포노티로신; p-요오도-페닐알라닌; 4-플루오로페닐글리신; p-브로모페닐알라닌; p-아미노-L-페닐알라닌; 이소프로필-L-페닐알라닌; L-3-(2-나프틸)알라닌; 아미노-, 이소프로필-, 또는 O-알릴-함유 페닐알라닌 유사체; 도파, O-메탈-L-티로신; 당화된 아미노산; p-(프로파르길록시)페닐알라닌; 디메틸-라이신; 하이드록시-프롤린; 머캅토프로피오닌산; 메틸-라이신; 3-니트로-티로신; 노르루신; 피로-글루타민산; Z(카르보벤족실); ε-아세틸-라이신; β-알라닌; 아미노벤조일 유도체; 아미노부티르산(Abu); 시트룰린; 아미노헥사노익산; 아미노이소부티르산; 사이클로헥실알라닌; d-사이클로헥실알라닌; 하이들록시프롤린; 니트로-아르기닌; 니트로-페닐알라닌; 니트로-티로신; 노르발린; 옥타하이드로인돌 카르복실레이트; 오르니틴; 페니실아민; 테트라하이드로이소퀴놀린; 아세타미도메틸 보호된 아미노산 및 페길화된 아미노산. 비천연성 아미노산 및 아미노산 유사체의 다른 예들을 미국 특허 제 20030108885호 및 제 20030082575호와 이들에 인용된 문헌들에서 확인할 수 있다.
일부 예에서 아미노산은 천연의 비필수 아미노산, 예컨대 타우린으로 치환될 수 있다.
비천연성 아미노산을 포함하는 펩티드 제조 방법은, 예컨대 미국 특허 제 20030108885호, 제 20030082575호, Deiters et al., J Am Chem Soc.(2003) 125:11782-3, Chin et al., Science(2003) 301:964-7 및 이들에 인용된 문헌들에서 확인할 수 있다.
또한, 비천연성 아미노산을 포함하는 펩티드는 국제 특허 W002086075에 개시된 방법으로 제조할 수 있다.
본 발명의 펩티드는 다른 결합으로 치환된 하나 이상의 일반적인 결합을 가질 수 있다. 이러한 치환으로 펩티드의 안정성을 높일 수 있다. 예컨대, 다른 결합으로 Cys18과 Xaa19 사이의 펩티드 결합을 치환하는 경우, 카르복시 펩티다제에 의한 절단을 낮출 수 있으며 소화관내에서의 반감기를 증가시킬 수 있다. 펩티드 결합을 대체할 수 있는 결합으로는, 레트로-인버스(retro-inverso) 결합(NH-C(0) 대신 C(O)-NH); 환원된 아미드 결합(NH-CH2); 티오메틸렌 결합(S-CH2 또는 CH2-S); 옥소메틸렌 결합(O-CH2 또는 CH2-O); 에틸렌 결합(CH2-CH2); 티오아미드 결합(C(S)-NH); 트랜스-올레핀 결합(CH=CH); 플루오로 치환된 트랜스-올레핀 결합(CF=CH); 케토메틸렌 결합(C(O)-CHR 또는 CHR-C(O), R은 H 또는 CH3임); 및 플루오로-케토메틸렌 결합(C(O)-CFR 또는 CFR-C(0), R은 H 또는 F 또는 CH3임).
본 발명의 펩티드는 표준 변형 방법을 이용하여 변형시킬 수 있다. 변형은 아미노(N-), 카르복시(C-) 말단에, 중간에 또는 이의 임의 조합에 발생될 수 있다. 본 발명의 일 측면에서, 펩티드의 하나 이상의 변형이 있을 수 있다. 변형으로는, 아세틸화, 아미드화, 바이오틴화, 신나몰화, 파르네실화, 포르밀화, 미리스토일화, 팔미톨화, 포스포릴화(Ser, Tyr, Thr), 스테아로일화, 숙시닐화, 설푸릴화, 및 사이클화(이황화 결합 또는 아미드 환화를 통함) 및 Cy3 또는 Cy5에 의한 변형을 포함하나, 이로 한정되는 것은 아니다. 본 발명의 펩티드는 또한, 2,4-디니트로페닐(DNP), DNP-라이신, 7-아미노-4-메탈-쿠마린(AMC), 플루오레세인, NBD(7-니트로벤즈-2-옥사-1,3-디아졸), p-니트로-아닐리드, 로다민 B, EDANS(5-((2-아미노에틸)아미노)나프탈렌-1-설폰산), 답킬(dabcyl), 답실(dabsyl), 단실, 텍사스 레드, FMOC 및 Tamra(테트라메틸로다민)에 의해 변형될 수 있다. 또한, 본 발명의 펩티드는 예컨데 폴리에틸렌 글리콜(PEG); 알킬 기(예, C1-C20 직쇄 또는 분지형의 알킬기); 지방산 라디칼; PEG, 알킬기 및 지방산 라디칼의 조합(미국 특허 제 6,309,633호; Soltero et al., 2001 Innovations in Pharmaceutical Technology 106-110); BSA 및 KLH (Keyhole Limpet Hemocyanin)와 접합시킬 수 있다.
본 발명의 펩티드 및 작용제는 당 모이어티를 합성으로 첨가하거나(WO 8 8/02756; WO 89/09786; DE 3910667Al, EP 0 374 089 A2; 및 미국 특허 4,861,755), 또는 양이온성 앵커(cationic anchor)(EP0363589), 지질 모이어티(WO 91/09837; 미국 특허 4,837,303) 또는 US5552520의 화합물 I, II 및 III으로 나타낸 치환기를 첨가함으로써, 치료학적 활성을 증가시키기 위해, 화학적으로 변형시킬 수 있다.
Xaa9가 Trp, Tyr 또는 Phe이거나, 또는 Xaa16 Trp인 경우, 펩티드는 절단으로 펩티드에 의한 GC-C 수용체 결합성을 변이시킬 수 있는 위치에 있는 기능성 키모트립신 절단 부위를 가질 가능성이 있다. Xaa9가 Lys 또는 Arg이거나, 또는 Xaa16 Lys 또는 Arg인 경우, 펩티드는 절단으로 펩티드에 의한 GC-C 수용체 결합성을 변이시킬 수 있는 위치에 있는 기능성 트립신 절단 부위를 가질 가능성이 있다.
상기 Xaa19가 Trp, Tyr 또는 Phe이면, 상기 펩티드는 절단시 펩티드의 카르복시 말단에서 Xaa19까지의 부분을 해리시키는 위치에 있는 키모트립신 절단 부위를 갖는다. 상기 Xaa19가 Leu, Ile 또는 Val이면, 상기 펩티드는 절단시 펩티드의 아미노 말단 부위에서 Xaa19까지의 부분을 해리시키는 위치에 있는 키모트립신 절단 부위를 갖는다. 상기 Xaa19가 His이면 비교적 높은 pH에서 동일한 효과가 있다. 상기 Xaa19가 Lys 또는 Arg이면, 상기 펩티드는 절단시 펩티드의 카르복시 말단 부위에서 Xaa19까지의 부분을 해리시키는 위치에 있는 트립신 절단 부위를 갖는다. 따라서, 만약 상기 펩티드가 Xaa19에 진통성 펩티드의 카르복시 말단을 포함한다면, 상기 펩티드는 적합한 프로테이즈에 노출시 소화관에서 유리될 것이다. 펩티드에 포함될 수 있거나 또는 펩티드와 함께 투여될 수 있는 진통성 펩티드로는 AspPhe(Xaa20Xaa21), 엔도모르핀-1(endomorphin-l), 엔도포르핀-2, 노시스타틴(nocistatin), 달아르긴(dalargin), 루프론(lupron), 지코노티드(ziconotide), 물질 P 및 그외 본원에 기재된 진통성 펩티드가 있다. 이들 펩티드는, 예컨대 Xaa20Xaa21 치환에 이용할 수 있다.
Xaa1 또는 본 발명의 펩티드의 아미노 말단에 있는 아미노산(예, Xaa2 또는 Xaa3)이 Trp, Tyr 또는 Phe이면, 절단시 상기 펩티드의 아미노 말단에서 Xaa1(또는 Xaa2 또는 Xaa3)까지의 부위가 Xaal, Xaa2 또는 Xaa3과 함께 해리될 위치에 위치된 키모트립신 절단 부위를 갖는다. Xaa1 또는 본 발명의 펩티드의 아미노 말단에 있는 아미노산(예, Xaa2 또는 Xaa3)이 Lys 또는 Arg이면, 상기 펩티드는 절단시 상기 펩티드의 아미노산 말단 부위에서 Xaa1까지의 부위가 Xaal, Xaa2 또는 Xaa3과 함께 해리될 위치에 위치된 트립신 절단 부위를 갖는다. Xaa1 또는 본 발명의 펩티드의 아미노 말단에 있는 아미노산이 Leu, Ile 또는 Val이면, 상기 펩티드는 절단기 상기 펩티드의 아미노산 말단 부위에서 Xaa1까지의 부위가 해리될 위위에 위치된 키모트립신 절단 부위를 갖는다. 상기 Xaa1이 His이면 비교적 높은 pH에서 동일한 효과가 있다. 따라서, 예컨대 만약 상기 펩티드가 진통성 펩티드의 아미노 말단을 Xaa1에 포함한다면, 상기 펩티드는 적합한 프로테이즈에 노출시 소화관에서 유리될 것이다. 상기 펩티드에 포함될 수 있는 진통성 펩티드로는 AspPhe, 엔도모르핀-1, 엔도포르핀-2, 노시스타틴, 달아르긴, 루프론, 물질 P 및 그외 본원에 기재된 진통성 펩티드를 포함할 수 있다.
완전한 접힘(folding)이 이루어지면, 이황화 결합이 Cys6과 Cys11 사이에, Cys7과 Cys15 사이에, 그리고 Cys10과 Cys18 사이에 존재할 수 있다. 본 발명의 펩티드는 ST 펩티드와 일부 서열 유사성을 유지한다. 하지만, 상기 펩티드는 기능성을 개선시키는 아미노산의 변이 및/또는 부가를 포함할 수 있다. 상기한 변이는, 예컨대 활성의 증가 또는 감소시킬 수 있고(예, 펩티드의 장 운동을 자극하는 능력의 증가 또는 감소), 펩티드의 정확한 접힘 능력을 변이시킬 수 있고, 펩티드의 안정성을 변이시킬 수 있고, 펩티드의 GC-C 수용체 결합성 및/또는 독성을 감소시킬 수 있다. 일부 경우에서는, 상기 펩티드는 천연형 ST 펩티드 보다 더 적합하게 작용할 수 있다. 예컨대, 설사와 탈수증과 같은 부적절한 부작용을 제한할 수 있다.
일부 예들에 있어서, 정상적으로 이황화 결합을 형성하는 Cys 잔기의 하나 이상의 쌍에서 하나 또는 둘다의 일원은, 정상적인 이황화 결합 위치에 다른 내부 교차 연결을 형성하기 위하여, 호모시스테인, 페니실아민, 3-머캅토프롤린(3- mercaptoproline)(Kolodziej et al. 1996 Int J Pept Protein Res 48: 274), β,β 디메틸시스테인(Hunt et al. 1993 Int J Pept Protein Res 42: 249) 또는 디아미노프로피오닌산(Smith et al. 1978 J Med Chem 21: 117)으로 치환될 수 있다.
또한, 하나 이상의 이황화 결합은 대안적인 공유성 교차 연결, 예컨대 아미드 연결(-CH2CH(0)NHCH2- 또는 -CH2NHCH(0)CH2-), 에스테르 연결, 티오 에스테르 연결, 락탐 브릿지(bridge), 카바모일 연결, 유레아 연결, 티오유레아 연결, 포스포네이트 에스테르 연결, 알킬 연결(-CH2CH2CH2CH2-), 알케닐 연결(-CH2CH=CHCH2-), 에테르 연결(-CH2CH2OCH2- 또는 -CH2OCH2CH2-), 티오에테르 연결(-CH2CH2SCH2- 또는 -CH2SCH2CH2-), 아민 연결(-CH2CH2NHCH2- 또는 -CH2NHCH2CH2-), 또는 티오아미드 연결(-CH2CH(S)HNHCH2- 또는 -CH2NHCH(S)CH2-)로 치환될 수 있다. 예컨대, Ledu 등(Proc Nat'1 Acad. Sci. 100:11263-78, 2003)은 락탐 및 아미드 교차 연결 방법을 개시하였다. Schafmeister 등(J.Am. Chem. Soc. 122 : 5891, 2000)은 안정한 탄화수소 교차 연결을 설명하고 있다. 탄화수소 교차 연결은 하나 이상의 Grubbs 촉매(Materia, Inc. 및 Sigma-Aldrich에서 구입 가능, 예컨대 미국 특허 제 5,831,108호 및 제 6,111,121호에 개시됨)를 이용하여 복분해 (또는 포화된 탄화수소의 경우에는 수소화가 수반되는 복분해)를 통해 형성시킬 수 있다. 일부 경우들에서, 이러한 대안적인 교차 연결 형성시 Cys 잔기를 Lys 또는 Glu과 같은 다른 잔기나, 또는 비천연성 아미노산으로 치환한다. 또한, 락탐, 아미드 및 탄화수소 교차 연결로 Cys가 아닌 잔기가 있는 위치에서 아미노산을 연결하더라도 펩티드를 안정화시킬 수 있다. 이러한 교차-연결은 두개의 아미노산 또는 6개의 아미노산 간격으로 떨어져 있는 두개의 아미노산 간에 발생될 수 있다(예, Schafmeister et al. J. Am. Chem. Soc. 122:5891, 2000).
펩티드가 서열 (I): Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21, 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys Cys Glu Xaa9 Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Xaa20 Xaa21(II)이고, 상기 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5는 생략되거나, 및/또는 Xaa19 Xaa20Xaa21은 생략된 것일 경우, 펩티드는 여전히 부가적인 카르복시 말단 아미노산 또는 아미노 말단 아미노산 서열이나, 또는 둘 다를 함유할 수 있다. 예컨대, 상기 펩티드는 펩티드의 재조합 산물 생산을 촉진시키고 환자에게 상기 펩티드를 투여하기 전에 절단되는 아미노 말단 서열을 포함할 수 있다. 상기 펩티드는 또한 그외 아미노 말단의 아미노산 또는 카르복시 말단의 아미노산을 포함할 수 있다. 일부 경우에서, 상기 부가적인 아미노산은 펩티드를 보호하고, 펩티드를 안정화시키고 또는 펩티드의 활성을 변이시킨다. 일부 경우에서는, 이러한 부가적인 아미노산의 일부 또는 모두는 환자에게 투여 전에 제거한다. 상기 펩티드는 아미노 말단 또는 카르복시 말단이나, 또는 둘 다에 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 또는 그 이상의 아미노산을 포함하고 있다. 플랭킹 아미노산의 갯 수는 동일할 필요가 없다. 예컨대, 펩티드의 아미노 말단에는 10개의 부가적인 아미노산이 있을 수 있지만 카르복시 말단에는 없을 수 있다.
일 예에 있어서, 상기 펩티드는 아미노산 서열 (I): Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21을 포함하며, 상기 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5는 생략되며; 상기 Xaa8은 Glu이고; 상기 Xaa9는 Leu, Ile, Lys, Arg, Trp, Tyr 또는 Phe이고; 상기 Xaa12는 Asn이고; 상기 Xaa13은 Pro이고; 상기 Xaa14는 Ala이고; 상기 Xaa16은 Thr, Ala, Lys, Arg 또는 Trp이고; 상기 Xaa17은 Gly이고; 상기 Xaa19는 Tyr 또는 Leu이고; 및 상기 Xaa20 Xaa21은 AspPhe이거나 또는 생략된다. 상기 Xaa20 Xaa21 및/또는 상기 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5가 생략된 경우, 일부 예들에서는 부가적인 플랭킹 아미노산이 존재할 수 있다. 아미노산 서열 (I): Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21을 가지는 펩티드를 포함하는 조성물의 특정 예에서, 상기 펩티드는 표 1의 임의의 펩티드를 포함하지 않거나, 또는 표 1의 임의의 펩티드로 구성되지 않는다.
제2 측면에 있어서, 본 발명은 또한 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21(I), 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21(II)을 포함하거나, 구성되거나 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 치료 또는 예방 방법에 관한 것이다.
상기 펩티드는 진통성 펩티드 또는 본 발명에 기재된 물질을 비제한적으로 포함하는 진통성 화합물을 포함한 여러가지 다른 임의의 펩티드와 함께, 또는 링크된, 예컨대 공유 링크된 상태로 병용 투여될 수 있다.
아미노산, 비-아미노산, 펩티드 및 비-펩티드 스페이서(spacer)는 GC-C 수용체 작용제인 펩티드와 일부 다른 생물학적 기능을 갖는 펩티드, 예컨대 진통성 펩티드 또는 비만 치료에 사용되는 펩티드 사이에 위치될 수 있다. 링커(linker)는 생체내에서 플랭킹 펩티드로부터 절단될 수 있는 어느 것일 수 있으며, 또는 생체내에서 플랭킹 펩티드에 링크된 상태로 남아있는 어느 것일 수 있다. 예를들면, 글리신, 베타-알라닌, 글리실-글리신, 글리실-베타-알라닌, 감마-아미노부티르산, 6-아미노카프로익산, L-페닐알라닌, L-트립토판 및 글리실-L-발릴-L-페닐알라닌을 스페이서로서(Chaltin et al. 2003 Helvetica Chimica Acta 86: 533-547; Caliceti et al. 1993 FARMCO 48: 919-32), 폴리에틸렌 글리콜로서(Butterworth et al. 1987 J. Med. Chem 30: 1295-302) 및 말레이미드 유도체로서 (King et al. 2002 Tetrahedron Lett. 43: 1987-1990) 사용할 수 있다. 그외 다양한 링커들이 문헌에 개시되어 있다(Nestler 1996 Molecular Diversity 2: 35-42; Finn et al. 1984 Biochemistry 23: 2554-8; Cook et al. 1994 Tetrahedron Lett. 35: 6777-80; Brokx et al. 2002 Journal of Controlled Release 78: 115-123; Griffin et al. 2003 J. Am. Chem. Soc. 125:6517-6531 ; Robinson et al. 1998 Proc. Natl. Acad. Sci. USA 95: 5929-5934).
본 발명의 펩티드는 각각 동일하거나 또는 상이한 기능을 제공하는 하나, 또는 둘 이상에 부착될 수 있다. 예컨대, 펩티드는 진통성 분자와 비만 치료에 사용되는 펩티드에 연결될 수 있다. 펩티드 및 여러가지 모이어티는 여러가지 방법으로 배열될 수 있다. 예를 들어, 본 발명의 펩티드는 아미노산 말단에 진통성 펩티드가 연결되고, 카르복시 말단에 항-비만성 펩티드가 연결될 수 있다. 추가적인 모이어티는 펩티드와 직접적으로 공유결합되거나 또는 링커를 통해 연결될 수 있다.
본 발명의 펩티다는 환형 펩티드 또는 선형 펩티드일 수 있다. 또한, 동일한 펩티드의 여러 카피를 하나의 환형 또는 선형 펩티드에 병합시킬 수 있다.
펩티드는, 척추동물(예, 포유류) 종 또는 박테리아 종들의 천연 펩티드의 아미노산 서열을 포함할 수 있다. 또한 펩티드는 부분적인 또는 완전한 비천연성 펩티드일 수 있다. 본 발명의 범위에는 본 발명의 펩티드에 대응되는 펩티드 모방체(peptidomimetic)가 포함된다.
여러가지 예들에서, 환자는 위장병이 있으며; 환자는 위장 운동 장애, 만성 가성 장 폐쇄(chronic intestinal pseudo-obstruction), 만성 가성 대장폐쇄(colonic pseudo-obstruction), 크론씨 병, 십이지장-위 역류(duodenogastric reflux), 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속쓰림(functional heartburn), 위식도 역류성 질환(gastroesophageal reflux disease)(GERD), 위부전마비(gastroparesis), 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염(ulcerative colitis), 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제(opiate pain killer)의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비)로 이루어진 군으로부터 선택된 질병이 있으며; 환자는 위장 운동 장애, 만성 가성 장 폐쇄, 만성 가성 대장폐쇄, 크론씨 병, 십이지장-위 역류, 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속쓰림, 위식도 역류성 질환, 위부전마비, 염증성 장 질환, 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염, 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비)이 있으며; 상기 조성물은 경구 투여되며.; 펩티드는 30개 이하의 아미노산을 포함하고, 펩티드는 20개 이하의 아미노산을 포함하고 및 펩티드는 5개 이하의 아미노산을 Cys6 상위에 포함하며; 펩티드는 150개 이하, 140개 이하, 130개 이하, 120개 이하, 110개 이하, 100개 이하, 90개 이하, 80개 이하, 70개 이하, 60개 이하, 50개 이하, 40개 이하 또는 30개 이하의 아미노산을 포함한다. 다른 예들에서는, 펩티드는 20개 이하의 아미노산을 포함한다. 다른 예들에서는, 펩티드는 20개 이하의, 15개 이하의, 10개 이하의 또는 5개 이하의 펩티드를 Cys18 다음에 포함한다. 특정 예들에서는, Xaa19는 키모트립신 또는 트립신 절단 부위이고, 진통성 펩티드는 Xaa19 바로 다음에 존재한다.
제3 측면에 있어서, 본 발명은 변비가 있는 환자를 치료하는 방법에 관한 것이다. 변비를 정의하는 임상적 판단 기준은 배변 빈도, 배변 일관성 및 배변 용이성의 범위이다. 변비의 일반적인 정의는 1주일 당 3회 미만의 배변을 의미한다. 다르게는 변비의 정의로 비정상적으로 딱딱한 변 또는 과다한 힘주기가 포함된다(Schiller 2001, Aliment Pharmacol Ther 15: 749-763). 변비는 특발성(기능적 변비 또는 서행성 변비)이거나 또는 신경 질환, 대사 질환 또는 내분비 질환을 포함한 기타 원인에 부수적인 것일 수 있다. 이러한 질환들로는 당뇨병, 갑상선저하증(hypothyroidism), 갑상선과다증(hyperthyroidism), 저칼슘혈증(hypocalcaemia), 다발성 경화증(Multiple Sclerosis), 파킨슨 병, 척수 병변(spinal cord lesion), 신경섬유종증(Neurofibromatosis), 자율신경병증(autonomic neuropathy), 샤가스병(Chagas disease), 거대결장증(Hirschsprung's disease) 및 낭성 섬유증(Cystic fibrosis)을 포함한다. 또한 변비는 수술의 결과(수술후 장 막힘증)일 수 있으며, 또는 진통제(오피오이드계), 항고혈압제, 항경련제, 항우울증제, 진경제(antispasmodic) 및 항정신이상제와 같은 약물 사용이 원인일 수 있다. 상기 방법은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I), 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 펩티드를 포함하는 또는 필수적으로 구성된 약학적 조성물을 투여하는 단계를 포함한다.
여러가지 예에 있어서, 변비는 치료제의 사용과 관련있으며; 변비는 신경 질환과 관련있으며; 변비는 수술후 변비(수술후 장 폐쇄증)이며; 변비는 위장병과 관련있으며; 변비는 특발성(기능적 변비 또는 서행성 변비)이며; 변비는 신경 질환, 대사 질환 또는 내분비 질환과 관련있다(예, 당뇨병, 갑상선저하증, 갑상선과다증, 저칼슘혈증, 다발성 경화증, 파킨슨 병, 척수 병변, 신경섬유종증, 자율신경병증, 샤가스병, 거대결장증 및 낭성 섬유증). 또한, 변비는 수술의 결과(수술후 장 막힘증)일 수 있으며, 또는 진통제(예, 오피오이드), 항고혈압제, 항경련제, 항우울증제, 진경제(antispasmodic) 및 항정신이상제와 같은 약물 사용이 원인일 수 있다.
제4 측면에 있어서, 본 발명은 위장병 환자 치료 방법에 관한 것으로, 상기 방법은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 폴리펩티드를 포함하거나 또는 필수적으로 구성된 조성물을 환자에 투여하는 단계를 포함한다.
다양한 예들에서, 환자는 위장병이 있다; 환자는 위장 운동 장애, 만성 가성 장 폐쇄, 만성 가성 대장폐쇄, 크론씨 병, 십이지장-위 역류, 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속쓰림, 위식도 역류성 질환, 위부전마비, 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염, 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비), 비만, 울혈성 심부전증 또는 양성 전립선 비대증으로 이루어진 군으로부터 선택된 질병이 있다.
제5 측면으로, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하는 약학적 조성물을 환자에 투여하는 단계를 포함하는, 환자에서 위장 운동을 증가시키는 방법에 관한 것이다.
제6 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하는 약학적 조성물을 환자에 투여하는 단계를 포함하는, 장의 구아닐레이트 사이클라제(GC- C) 수용체의 활성(활성화)을 증가시키는 방법에 관한 것이다.
제7 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는 폴리펩티드를 코딩하는 뉴클레오티드 서열을 포함하는 분리된 핵산 분자에 관한 것이다.
제8 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클레이트(GC- C) 수용체에 대한 작용제를 투여하는 단계를 포함하는, 변비 치료 방법에 관한 것이다. 다양한 예들에서, 상기 작용제는 펩티드이고, 상기 펩티드는 하나의 이황화 결합을 형성하는 2개의 Cys을 함유하고 있으며, 상기 펩티드는 두개의 이황화 결합을 형성하는 4개의 Cys을 함유하고 있으며, 상기 펩티드는 3개의 이황화 결합을 형성하는 6개의 Cys을 함유하고 있다.
제9 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클라제(GC-C) 수용체에 대한 작용제를 경구로, 좌약제로 또는 비경구로 투여하는 단계를 포함하는, 위장병, 위장 운동 장애, 만성 가성 장 폐쇄, 만성 가성 대장폐쇄, 크론씨 병, 십이지장-위 역류, 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속쓰림, 위식도 역류성 질환, 위부전마비, 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염, 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비), 비만, 울혈성 심부전증 또는 양성 전립선 비대증의 치료방법에 관한 것이다. 다양한 예들에서, 상기 작용제는 펩티드이고, 상기 펩티드는 하나의 이황화 결합을 형성하는 2개의 Cys을 함유하고 있으며, 상기 펩티드는 두개의 이황화 결합을 형성하는 4개의 Cys을 함유하고 있으며, 상기 펩티드는 3개의 이황화 결합을 형성하는 6개의 Cys을 함유하고 있다.
제 10 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클라제(GC-C) 수용체에 대한 작용제를 투여하는 단계를 포함하는, 위장 운동 장애, 만성 가성 장 폐쇄, 만성 가성 대장폐쇄, 크론씨 병, 십이지장-위 역류, 소화불량, 기능성 소화불량, 비궤양성 소화불량, 기능성 위장병, 기능성 속쓰림, 위식도 역류성 질환, 위부전마비, 과민성 장 증후군, 수술후 장폐색, 궤양성 직장염, 만성 변비, 및 변비 관련 질환 및 증상(예, 무통증 아편제의 사용과 관련된 변비, 수술후 변비, 신경성 질환 뿐만 아니라 본 발명에 기재된 그외 증상 및 질환과 관련된 변비)으로 이루어진 군으로부터 선택된 위장병의 치료방법에 관한 것이다. 다양한 예들에서, 상기 조성물은 경구로 투여되며; 상기 펩티드는 30개 이하의 아미노산을 포함하며; 상기 펩티드는 20개 이하의 아미노산을 포함하며, 및 상기 펩티드는 Cys5 상위에 5개 이하의 아미노산을 포함한다.
다양한 예들에서, 상기 작용제는 펩티드이고, 상기 펩티드는 하나의 이황화 결합을 형성하는 2개의 Cys을 함유하고 있으며, 상기 펩티드는 두개의 이황화 결합을 형성하는 4개의 Cys을 함유하고 있으며, 상기 펩티드는 3개의 이황화 결합을 형성하는 6개의 Cys을 함유하고 있다.
제11 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클라제(GC-C) 수용체에 대한 완전 또는 일부 작용제를 투여하는 단계를 포함하는, 비만 치료 방법에 관한 것이다. 다양한 예들에서, 상기 작용제는 펩티드이고, 상기 펩티드는 하나의 이황화 결합을 형성하는 2개의 Cys을 함유하고 있으며, 상기 펩티드는 두개의 이황화 결합을 형성하는 4개의 Cys을 함유하고 있으며, 상기 펩티드는 3개의 이황화 결합을 형성하는 6개의 Cys을 함유하고 있다. 상기 작용제는 단독으로 또는 본원에 기재된 항-비만제를 비제한적으로 포함하는 하나 이상의 비만 치료제와 병용 투여될 수 있다. 따라서, 예컨대, PYY3 -36을 본 발명의 펩티드의 카르복시 또는 아미노 말단에 융합시킬 수 있다. 이러한 융합 단백질은 두개의 펩티드를 절단하여 분리할 수 있는 키모트립신 또는 트립신 절단부를 포함할 수 있다.
제12 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 비만 치료 방법에 관한 것이다.
제 13 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 조성물에 관한 것이다. 일 예로, 상기 조성물은 약학적 조성물이다.
제 14 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 울혈성 심부전증의 치료 방법에 관한 것이다.
상기 펩티드는 그외 울혈성 심부전증 치료제, 예컨대 심방성 나트륨 이뇨 펨티드, 뇌성 나트륨 이뇨 펩티드 또는 C형 나트륨 이뇨 펩티드와 같은 나트륨 이뇨 펩티드, 이뇨제 또는 안지오텐신 전환 효소 저해제와 함께 병용 투여될 수 있다.
제 15 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하는 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 양성 전립선 비대증의 치료 방법에 관한 것이다. 상기 펩티드는 그외 BPH 치료제, 예컨대 5-알파 리덕타아제 저해제(예, 피나스테리드) 또는 알파 아드레날린성 저해제(예, 독사조신)와 병용 투여될 수 있다.
제 16 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 내장 통증, 위장병과 관련된 통증 또는 그외 질환과 관련된 통증을 포함하는 통증을 치료 또는 경감시키는 방법에 관한 것이다.
제 17 측면에 있어서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하는 약학적 조성물을 환자에게 투여하는 단계를 포함하는, 위장관의 염증을 포함한 염증, 예컨대 위장병 관련 염증, 감염 관련 염증 또는 그외 질병 관련 염증의 치료 방법에 관한 것이다.
제 18 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클라제(GC-C) 수용체에 대한 완전 또는 부분 작용제를 투여하는 단계를 포함하는 울혈성 심부전증의 치료 방법에 관한 것이다. 상기 작용제는 단독으로 또는 그외 울혈성 심부전증 치료제, 예컨대 심방성 나트륨 이뇨 펩티드, 뇌성 나트륨 이뇨 펩티드 또는 C형 나트륨 이뇨 펩티드와 같은 나트륨 이뇨 펩티드, 이뇨제 또는 안지오텐신 전환 효소 저해제와 함께 병용 투여될 수 있다.
제 19 측면에 있어서, 본 발명은 장의 구아닐레이트 사이클라제(GC-C) 수용체에 대한 완전 또는 부분 작용제를 투여하는 단계를 포함하는, 양성 전립선 비대증의 치료 방법에 관한 것이다. 상기 작용제는 단독으로, 또는 그외 BPH 치료제, 예컨대 5-알파 리덕타아제 저해제(예, 피나스테리드) 또는 알파 아드레날린성 저해제(예, 독사조신)와 병용 투여될 수 있다.
제 20 측면에 있어서, 본 발명은 본 발명에 따른 펩티드를 코딩하는 서열을 포함하는 분리된 핵산 분자에 관한 것이다. 또한, 벡터, 예컨대 본 발명에 따른 펩티드를 배양 세포(진핵 세포 또는 원핵 세포)에서 발현시키기 위해 사용될 수 있는 상기 핵산 분자를 포함하는 발현 벡터도 본 발명에 포함된다. 벡터는 또한 하나 이상의 조절성 인자, 예컨대 이종의 프로모터 또는 상기 펩티드를 코딩하는 서열과 작동가능하게 연결된 번역에 필요한 인자를 추가적으로 포함할 수 있다. 일부 경우에서, 핵산 분자는 본 발명에 따른 펩티드의 아미노산 서열을 포함하는 아미노산 서열을 코딩할 것이다. 예컨대, 핵산 분자는 본 발명에 따른 펩티드를 제조하기 위해 처리될 수 있는 프리단백질 또는 프리프로단백질을 코딩할 수 있다.
본 발명에 따른 펩티드 또는 본 발명의 펩티드를 포함하는 펩티드나 폴리펩티드를 코딩하는 뉴클레오티드 서열을 포함한는 핵산은, RNA 또는 DNA일수 있으며, 단일 또는 이중 가닥일 수 있으며, 원핵성, 진핵성 또는 바이러스로부터 유래된 것일 수 있다. 벡터는 트랜스포존, 바이러스 벡터, 에피솜(예, 플라스미드), 염색체 삽입체 및 인공 염색체(예, BAC 또는 YAC)를 포함할 수 있다. 코딩된 펩티드나 폴리펩티드의 발현을 위한 적합한 세균 숙주로는, E. coli가 있으나, 이로 한정되진 않는다. 적합한 진핵 숙주로는 사카로마이세스 세레비지애와 같은 효모, 그외 진균류, 척수동물 세포, 무척추동물 세포(예, 곤충 세포), 식물 세포, 인간 세포, 인간 조직 세포 및 전체 진핵 유기체(예, 형질전환 식물 또는 형질전환 동물)가 있다. 또한, 벡터의 핵산을 사용하여 백시니아 또는 베쿨로바이러스(예, Bac- to Bac-® 베쿨로바이러스 발현 시스템 이용(Invitrogen Life Technologies, Carlsbad, CA))와 같은 바이러스를 형질감염시키는데 이용할 수 있다.
전술한 바와 같이, 본 발명은 본 발명에 따른 펩티드 또는 상기한 펩티드를 포함하는 펩티드나 폴리펩티드의 제조에 적합한 벡터 또는 유전자 구조체를 포함한다. 일반적으로, 상기 유전자 구조체는 또한, 코딩 핵산 분자 뿐만 아니라 프로모터 및 조절성 서열과 같이 발현을 허용하는 인자를 포함한다. 발현 벡터는 프로모터, 인핸서, 오퍼레이터 및 억제 서열과 같은 전사 개시를 조절하는 전사 조절 서열을 포함할 수 있다. 다양한 전사 조절 서열들이 당업계에 널리 공지되어 있으며, 비제한적으로, 세균, 효모, 식물 또는 동물 세포에서 기능할 수도 있다. 발현 벡터는 또한 번역 조절 서열(예, 비번역성 5' 서열, 비번역성 3' 서열, 폴리 A 첨가 부위 또는 내부 라이보좀 도입부), 스플라이싱 서열 또는 스플라이싱 조절 서열, 및 전사 종결 서열을 포함할 수 있다. 벡터는 자가 복제할 수 있거나 또는 숙주 DNA로 삽입될 수 있다.
또한, 본 발명은 외부 핵산 분자들중 하나를 가지고 있는 분리된 숙주 세포 및 상기한 세포를 배양하여 펩티드 또는 펩티드 전구체의 회수에 의한 펩티드 제조 방법에 관한 것이다. 펩티드 또는 전구체의 회수는 배양액 수거를 수반할 수 있으며, 추가적인 정제 단계가 수반되지 않을 수 있다. 그러나, 본 발명의 단백질은 친화성 크로마토그래피, 열성 침전, 면역친화성 크로마토그래피, 암모늄 설페이트 침전, 이온 교환 크로마토그래피, 여과, 전기영동 및 소수성의 상호작용 크로마토그래피와 같은 비제한적인 표준 정제 기법을 이용하여 정제할 수 있다.
펩티드는 정제될 수 있다. 정제된 펩티드는 그외 단백질, 지질 및 핵산으로부터, 또는 합성된 화합물들로부터 분리된 펩티드이다. 폴리펩티드는 전제한 조제물의 건조 중량 대비 10, 20, 50, 70, 80 또는 95% 이상을 구성할 수 있다.
제21 측면에서, 본 발명은 아미노산 서열: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21 (I) 또는 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Asn12 Pro13 Ala14 Cys15 Xaa16 Gly17 Cys18 Xaa19 Xaa20 Xaa21 (II)을 포함하는, 구성된 또는 필수적으로 구성된 정제된 펩티드를 포함하거나 또는 필수적으로 구성된 조성물을 환자에게 투여함에 의한, 기관, 조직(예, 장 점막), 또는 세포(GC-A 수용체가 있는 세포)에서 환형 구아노신 3'-모노포스페이트(cGMP)의 수준을 증가시키는 방법에 관한 것이다.
제 22 측면에서, 본 발명은 하기 아미노산 서열을 포함하는, 구성된 또는 필수적으로 구성된 폴리펩티드에 관한 것이다: Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21로, 상기에서 a) Xaa8 또는 Xaa9 존재하지 않거나; b) Xaa8과 Xaa9 어느 것도 존재하지 않거나; c) Xaa12, Xaa13 및 Xaa14중 어느 하나는 존재하지 않거나; d)Xaa12, Xaa13 및 Xaa14중 어느 둘은 존재하지 않거나; e) Xaa12, Xaa13 및 Xaa14 존재하지 않거나; f) Xaa16 및 Xaa17 중 어느 하나는 존재하지 않거나; g) Xaa16와 Xaa17 어느 것도 존재하지 않거나, 이들의 조합이다. 다양한 예들에서, Xaa1 Xaa2 Xaa3 Xaa4 및 Xaa5 중 하나, 둘, 셋, 넷 또는 다섯은 존재하지 않는다. 다른 예로, Xaa19 Xaa20 및 Xaa21 중 하나, 둘 또는 셋은 생략된다.
제 23 측면에서, 본 발명은 본 발명의 펩티드 또는 작용제 및 약학적으로 허용가능한 담체를 포함하거나, 으로 구성되거나 또는 필수적으로 구성된 약학적 조성물을 투여하는 단계를 포함하는, cGMP 수준을 증가시킴으로써 개선되는 질병을 치료하는 방법에 관한 것이다.
유용한 펩티드들은 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys Cys Glu Xaa9 Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr Xaa20 Xaa21(II)(서열번호)의 아미노산 서열을 필수적으로 포함하거나, 구성되거나 또는 필수적으로 구성된 펩티드인 아래 펩티드이다:
Figure 112006072578425-pct00003
Figure 112006072578425-pct00004
Figure 112006072578425-pct00005
또한, 유용한 펩티드는 하기 서열들중 어느 하나를 포함하거나, 구성되거나 또는 필수적으로 구성된다:
Figure 112006072578425-pct00006
Figure 112006072578425-pct00007
Figure 112006072578425-pct00008
Figure 112006072578425-pct00009
Figure 112006072578425-pct00010
Figure 112006072578425-pct00011
Figure 112006072578425-pct00012
Figure 112006072578425-pct00013
Figure 112006072578425-pct00014
Figure 112006072578425-pct00015
Figure 112006072578425-pct00016
Figure 112006072578425-pct00017
Figure 112006072578425-pct00018
Figure 112006072578425-pct00019
또한, 본 발명은 Cys(또는 Cys 치환용 아미노산, 예컨대 다른 아미노산과 공유 결합을 형성할 수 있는 아미노산) 이외의 1, 2, 3 또는 4개의 아미노산이 결손된, 본 명세서에 기재된 임의 펩티드의 결손 변이체에 관한 것이다. 2개(또는 그 이상)의 아미노산이 결손되고 펩티드가 Cysa Cysb Xaa Xaa Cysc Cysd Xaa Xaa Xaa Cyse Xaa Xaa Cysf를 포함하는 경우, 일부 예들에서, Cysb와 Cysc 사이에 및/또는 Cysd와 Cyse 사이에 및/또는 Cyse와 Cysf 사이에 둘 이상의 결손이 있을 수 있다. 그러나, 다른 예의 경우, Cysb와 Cysc 사이에 또는 Cysd와 Cyse 사이에 또는 Cyse와 Cysf 사이에 대부분 하나의 결손이 있다. 따라서, 본 발명은 a) Cysb와 Cysc 사이에 아미노산 하나가 결손되거나; b) Cysd와 Cyse 사이에 아미노산 하나가 결손되거나; c) Cyse와 Cysf 사이에 아미노산 하나가 결손되거나; d) Cysb와 Cysc 사이에 아미노산 하나가 결손되고, Cysd와 Cyse 사이에 아미노산 하나가 결손되거나; e) Cysd와 Cyse 사이에 아미노산 하나가 결손되고 Cyse와 Cysf 사이에 아미노산 하나가 결손되거나; f) Cysb와 Cysc 사이에 아미노산 하나가 결손되고, Cyse와 Cysf 사이에 아미노산 하나가 결손되거나; 또는 g) Cysb와 Cysc 사이에 아미노산 하나가 결손되고, Cysd와 Cyse 사이에 아미노산 하나가 결손되고, Cyse와 Cysf 사이에 아미노산 하나가 결손된, 서열 Cysa Cysb Xaa Xaa Cysc Cysd Xaa Xaa Xaa Cyse Xaa Xaa Cysf을 포함하는 본원의 모든 펩티드를 포함한다. 특정 예에서, 여러가지 결손 변이체는 GC-C 수용체에 결합하거나/결합하여 활성화하는 펩티드이다. 여러 예들에서, 상기 여러가지 결손 변이체는 cGMP 수준을 증가시키는 펩티드이다.
Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 3)의 결손 변이체는 도 11에 나열된 펩티드를 포함한다. 이러한 결손 변이체에서, 모든 아미노산들이 결손될 수 있으며, Cys를 제외한 1, 2, 3 또는 4개의 아미노산이 결손될 수 있다.
또한, 본 발명은 펩티드내 임의 아미노산 앞에 또는 뒤에 1, 2, 3 또는 4 개의 아미노산(예, Gly 또는 Ala)이 삽입된, 본원에 기재된 모든 펩티드의 삽입 변이체에 관한 것이다. 일부 예들에서, 하나의 아미노산이 두개의 Cys 사이에 삽입된다. 예컨대, 둘 이상의 아미노산이 삽입되어 있으며, 펩티드가 서열 Cysa Cysb Xaa Xaa Cysc Cysd Xaa Xaa Xaa Cyse Xaa Xaa Cysf를 포함하는 경우, 일부 예들에서, Cysb와 Cysc 사이에 또는 Cysd와 Cyse 사이에 또는 Cyse와 Cysf 사이에 둘 이상의 아미노산이 삽입된다. 그러나, 다른 예의 경우, Cysb와 Cysc 사이에 또는 Cysd와 Cyse 사이에 또는 Cyse와 Cysf 사이에 아미노산 하나가 삽입된다. 따라서, 본 발명은 a) Cysb와 Cysc 사이에 아미노산 하나가 삽입되거나; b) Cysd와 Cyse 사이에 아미노산 하나가 삽입되거나; c) Cyse와 Cysf 사이에 아미노산 하나가 삽입되거나; d) Cysb와 Cysc 사이에 아미노산 하나가 삽입되고, Cysd와 Cyse 사이에 아미노산 하나가 삽입되거나; e) Cysd와 Cyse 사이에 아미노산 하나가 삽입되고 Cyse와 Cysf 사이에 아미노산 하나가 삽입되거나; f) Cysb와 Cysc 사이에 아미노산 하나가 삽입되고, Cyse와 Cysf 사이에 아미노산 하나가 삽입되거나; 또는 g) Cysb와 Cysc 사이에 아미노산 하나가 삽입되고, Cysd와 Cyse 사이에 아미노산 하나가 삽입되고, Cyse와 Cysf 사이에 아미노산 하나가 삽입된, 서열 Cysa Cysb Xaa Xaa Cysc Cysd Xaa Xaa Xaa Cyse Xaa Xaa Cysf을 포함하는 본원의 임의의 펩티드에 관한 것이다. 또한, 하나 이상의 아미노산을 Cysa 앞에 삽입시킬 수 있으며, 및/또는 하나 이상의 아미노산을 Cysf 뒤에 삽입할 수 있다.
다양한 예들에서, 여러가지 삽입 변이체들은 GC-C 수용체에 결합하거나/결합하여 활성화하는 펩티드이다. 다양한 예들에서, 상기 여러가지 삽입 변이체는 cGMP 수준을 증가시키는 펩티드이다.
삽입 변이체 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 3)은 각 아미노산 뒤에 최대 아미노산 4개가 삽입될 수 있는 것을 포함한다. 따라서, 본 발명은 서열: Cys Xaa(0-4) Cys Xaa(0-4) Glu Xaa(0-4) Tyr Xaa(0-4) Cys Xaa(0-4) Cys Xaa(0-4) Asn Xaa(0-4) Pro Xaa(0-4) Ala Xaa(0-4) Cys Xaa(0-4) Thr Xaa(0-4) Gly Xaa(0-4) Cys Xaa(0-4) Tyr Xaa(0-4) (서열번호)을 포함하는 펩티드를 포함한다. 상기 삽입된 아미노산은 임의의 아미노산 또는 아미노산 유사체(천연 또는 비천연성)일 수 있으며, 동일하거나 상이한 것일 수 있다. 특정 예에서, 상기 삽입된 아미노산은 모두 Gly이거나 Ala이거나, 또는 Gly와 Ala의 조합일 수 있다.
도 12는 서열 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 3)을 가지는 펩티드의 삽입 변이체를 나타낸다.
또한, 본 발명은 서열 Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Cys6 Cys7 Xaa8 Xaa9 Cys10 Cys11 Xaa12 Xaa13 Xaa14 Cys15 Xaa16 Xaa17 Cys18 Xaa19 Xaa20 Xaa21을 가지는 펩티드의 변이체, 최대 아미노산 4개가 삽입되거나 및/또는 결손된 형태의 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 3)의 변이체에 관한 것이다. 삽입 및 결손은 서열번호 1의 Cys6과 Cys18 사이에서 이루어질 수 있으며, 또는 서열번호 1에서 Cys6의 아미노 말단이나 및/또는 Cys18의 카르복시 말단에서 이루어질 수 있다.
또한, 본 발명은 하나 이상의 펩티드 변형, 하나 이상의 비천연성 아미노산 또는 아미노산 유사체, 하나 이상의 이황화 결합 대안체 또는 본원에 기재된 하나 이상의 대안적인 펩티드 결합을 포함할 수 있는 펩티드에 관한 것이다.
본 발명의 펩티드는 반대이온(counterion)과 함께 존재할 수 있다. 유용한 반대이온으로는 다음의 염이 있다: 아세테이트, 벤젠설포네이트, 벤조에이트, 칼슘 에디테이트(calcium edetate), 캄실레이트(camsylate), 카르보네이트, 시트레이트, 에디테이트(EDTA), 에디실레이트(edisylate), 엠보네이트(embonate), 에실레이트(esylate), 퓨마레이트, 글루셉테이트(gluceptate), 글루코네이트, 글루타메이트, 글리콜릴아르사닐레이트(glycollylarsanilate), 헥실레소르시네이트(hexylresorcinate), 요오드화물(iodide), 브로마이드, 클로라이드, 하이드록시나프토에이트(hydroxynaphthoate), 이세티오네이트(isethionate), 락테이트, 락토비오네이트, 에스톨레이트(estolate), 말리에이트(maleate), 말레이트(malate), 만델레이트(mandelate), 메실레이트(mesylate), 뮤케이트(mucate), 냅실레이트(napsylate), 니트레이트, 판토테네이트(pantothenate), 포스페이트, 살리실레이트, 스테아레이트, 숙시네이트, 설페이트, 타르타레이트, 테오클레이트(theoclate), 아세트아미도벤조에이트, 아디페이트, 알기네이트, 아미노살리실레이트, 안하이드로메틸렌시트레이트, 아스코르베이트, 아스파르테이트, 캄포레이트, 카프레이트, 카르포에이트, 카프릴레이트, 신나메이트, 사이클라메이트, 디클로로아세테이트, 포르메이트, 젠티세이트, 글루쿠로네이트, 글리세로포스페이트, 글리콜레이트, 히퓨레이트(hippurate), 플루오라이드, 말로네이트, 나파디실레이트(napadisylate), 니코티네이트, 올레이트(oleate), 오로테이트(orotate), 옥살레이트, 옥소글루타레이트, 팔미테이트, 펙티네이트, 펙티네이트 폴리머, 페닐에틸바르비튜레이트, 피크레이트, 프로피오네이트, 피돌레이트(pidolate), 세바케이트(sebacate), 로다나이드, 토실레이트 및 탄네이트(tannate).
펩티드 및 장의 구아닐레이트 사이클라제(GC-C) 수용체의 작용제를 사용하여, 변비, 장 운동성 저하를 치료하거나 또는 소화 또는 공복(stomach emptying) 서행을 치료하는데 사용할 수 있다. 펩티드는 한가지 이상의 lBS(팽만감, 통증, 변비), GERD(식도로 산 역류), 십이지장 위 역류, 기능성 소화불량, 또는 위부전마비(메스꺼움, 구토, 팽만감, 위 배출 지체) 및 그외 본원에 기재된 질환의 증상을 완화하는데 사용할 수 있다.
본 발명의 구체적인 실시예를 하나 이상을 첨부된 명세서에 기재한다. 모든 공개물, 특허 및 특허 출원은 참조문헌로서 원용된다.
발명의 상세한 설명
본 발명의 펩티드는 장에서 유액 및 전해질 균형에 주된 조절자인 장의 구아닐레이트 사이클라제(GC-C) 수용체에 결합한다. 자극을 받으면, 장 상피세포 표면의 첨막(apical membrane)에 위치한 상기 수용체에서는 장 상피세포의 사이클릭 GMP(cGMP) 증가가 유발된다. cGMP 증가는 물과 나트륨 흡수 감소와, 염소 및 칼슘 이온 분비 증가를 초래하여, 장 액 및 전해질 이동을 변이시키고 장 운동성을 증가시키는 것으로 보여진다. 장의 GC-C 수용체는 세포외 리간드 결합 부위, 트랜스멤브레인 부위, 세포내 단백질 키나제 유사 부위 및 사이클라제 촉매성 도메인을 가지고 있다. GC-C 수용체의 기능은, 유액 및 전해질 항상성, 상피 세포의 증식 조절 및 세포자살 유발인 것으로 제안되어 있다(Shalubhai 2002 Curr Opin Drug Dis Devel 5: 261-268).
GC-C는 위장 상피 세포에 의해 장에서 발현될 뿐만 아니라, 신장, 폐, 췌장, 뇌하수체, 신장, 발생중인 간(reviewed in Vaandrager 2002, Mol Cell Biochem 230: 73-83)과, 수컷 및 암컷의 생식 조직(reviewed in Vaandrager 2002 Mol Cell Biochem 230: 73-83)을 포함한 장 이외의 조직들에서 발현된다. 이는 GC-C 수용체 작용제가 위장관 이외 질환, 예컨대 울혈성 심부전증 및 양성 전립선 비대증의 치료에 사용될 수 있음을 시사한다.
위에서 분비되는 펩티드성 호르몬인 그렐린(Ghrelin)은, 인간의 식욕을 조절하는 중요한 조절자이다. 그렐린 발현 수준은 단식과 위 공복에 의해 조절된다(Kim et al., 2003, Neuroreprt 14: 1317-20; Gualillo et al., 2003, FEBS Letts 552: 105-9). 따라서, 위장 운동성을 증가시킴으로써 GC-C 수용체 작용제를 비만 조절에 사용할 수 있다.
인간에서, GC-C 수용체는 구아닐린(Gn)(미국 특허 5,96,097), 유로구아닐린(uroguanylin)(Ugn)(미국 특허 5,140,102) 및 림포구안닐린(Forte et al., 1999, Endocrinology 140: 1800-1806)에 의해 활성화된다. 이러한 제제들은 흥미롭게도 박테리아로부터 유래된 펩티드 클래스, 즉 ST에 비해 10 -100 배 낮은 효능을 갖는다(reviewed in Gianella 1995 J Lab Clin Med 125: 173-181). ST 펩티드는 우수한 GC-C 작용제로 간주되며, 단백효소에 의한 분해에 매우 저항적이다.
ST 펩티드는 장 신경계를 자극할 수 있다(Rolfe et al., 1994, J Physiolo 475: 531-537; Rolfe et al., 1999, Gut 44: 615-619; Nzegwu et al., 1996, Exp Physiol 81: 313-315). 또한 cGMP는 다수 동물 통증 모델들에서 항통각 효과(antinociceptive effect)가 있는 것으로 보고된 바 있다(Lazaro Ibanez et al., 2001, Eur J Pharmacol 426: 39-44; Soares et al., 2001, British J Pharmacol 134: 127-131; Jain et al., 2001, Brain Res 909: 170-178; Amarante et al., 2002, Eur J Pharmacol 454: 19-23). 따라서 GC-C 작용제는 항염증 효과 뿐만 아니라 진통 효과 모두를 나타낼 수 있다.
박테리아에서, ST 펩티드는 일반적으로 70개 이상의 아미노산을 갖는 프리프로단백질로부터 유래된다. 상기 프리 및 프로 부위는 분비 과정의 일부분으로서 절단되며, 그 결과 생성된, 일반적으로 20개 미만의 아미노산을 함유한 성숙형 단백질은 생물학적 활성을 가지게 된다.
공지 박테리아의 ST 펩티드들로는, 성숙형의 아미노산 서열 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 _)을 갖는 E. coli ST Ib(Moseley et al.(1983) Infect. Immun. 39:1167), 성숙형의 아미노산 서열 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Ala Gly Cys Tyr(서열번호 _)을 갖는 E. coli ST Ia (So and McCarthy (1980) Proc. Natl. Acad. Sci. USA 77:4011); 성숙형의 아미노산 서열 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Tyr Pro Ala Cys Ala Gly Cys Asn(SEQ ID NO :)을 갖는 E. coli ST I* (Chan and Gialnnella (1981). J. Biol. Chem. 256: 7744); 성숙형의 아미노산 서열 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Ala Gly Cys Tyr(서열번호)을 갖는 C. 프레운디(freundii) ST 펩티드(Guarino et al. (1989) Infect. Immun. 57: 649); 후술되는 프로 형태의 아미노산 서열 Gln Ala Cys Asp Pro Pro Ser Pro Pro Ala Glu Val Ser Ser Asp Trp Asp Cys Cys Asp Val Cys Cys Asn Pro Ala Cys Ala Gly Cys(서열번호)(Ser-7을 Leu-7로 치환한 Y-STa 변이체), (Takao et al. (1985) Eur. J. Biochem. 152:199)을 갖는 Y. 엔테로콜리티카(enterocolitica) ST 펩티드, Y-ST (Y-STa), Y- STb 및 Y-STc(reviewed in Huang et al. (1997) Microb. Pathog 22: 89); Lys Ala Cys Asp Thr Gln Thr Pro Ser Pro Ser Glu Glu Asn Asp Asp Trp Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Ala Gly Cys(서열번호); Gln Glu Thr Ala Ser Gly Gln Val Gly Asp Val Ser Ser Ser Thr Ile Ala Thr Glu Val Ser Glu Ala Glu Cys Gly Thr Gln Ser Ala Thr Thr Gln Gly Glu Asn Asp Trp Asp Trp Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Phe Gly Cys(SEQ ID NO :); 성숙형 아미노산 서열 Ser Asp Trp Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Ala Gly Cys(서열번호)을 갖는 Y. 크리스텐세니(kristensenii) ST 펩티드; 성숙형 아미노산 서열 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu Asn(서열번호)을 갖는 V. 콜레라(cholerae) non-01 ST 펩티드(Takao et al. (1985) FEBS lett. 193: 250); 및 성숙형 아미노산 서열 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu Asn(서열번호)을 갖는 V. 미미쿠스(mimicus) ST 펩티드(Arita et al. (1991) FEMS Microbiol. Lett. 79: 105). 아래 표는 다양한 성숙형 ST 펩티드의 전체 또는 일부 서열을 나타낸다.
GenBank Accesion GenBand GI 서열
QHECIB 69638 NSSNYCCELCCNPACTGCY(서열번호 _)
P01559 123711 NTFYCCELCCNPACAGCY(서열번호 _)
AAA24653 147878 NTFYCCELCCNPACAPCY(서열번호 _)
P01560 123707 NTFYCCELCCYPACAGCN(서열번호 _)
AAA27561 295439 IDCCEICCNPACFGCLN(서열번호 _)
P04429 123712 IDCCEICCNPACFGCLN(서열번호 _)
S34671 421286 IDCCEICCNPACF(서열번호 _)
CAA52209 395161 IDCCEICCNPACFG(서열번호 _)
A54534 628844 IDCCEICCNPACFGCLN(서열번호 _)
AAL02159 15592919 IDRCCEICCNPACFGCLN(서열번호 _)
AAA18472 487395 DWDCCDVCCNPACAGC(서열번호 _)
S25659 282047 DWDCCDVCCNPACAGC(서열번호 _)
P74977 3913874 NDDWCCEVCCNPACAGC(서열번호 _)
BAA23656 2662339 WDWCCELCCNPACFGC(서열번호 _)
P31518 399947 SDWCCEVCCNPACAGC(서열번호 _)
QACDPPSPPAEVSSDWDCCDVCCDPAC AGC
QACDPPSPPAEVSSDWDCCDVCCNPACAG C
KACDTQTPSPSEENDDTCCEVCCNPACAG C
QETASGQVGDVSSSTIATEVSEAECGTQSATTQGE NDWDWCCELCCNPACFGC
MKKLMLAIFISVLSFPSFSQSTESLDSSKEKITLETKKCDVVKNNSEKKSENMNNTFYCCELCCNPACAGCY
MKKSILFIFLSVLSFSPFAQDAKPVESSKEKITLESKKCNIAKKSNKSGPESMNSSNYCCELCCNPACTGCY
MKKIVFVLVLMLSSFGAFGQETVSGQFSDALSTPITAEVYKQACDPPLPPA EVSSDWDCCDVCCNPACAGC
GNLIDCCEICCNPACFGCLN
GNLIDRCEICCNPACFGCLN
PPAEVSSDWDCCDVCCNPACAGC
E. coli ST-1A (ST-P) 단백질의 미성숙형(프리 및 프로 부위 포함함)은 서열 : mkklmlaifisvlsfpsfsqstesldsskekitletkkcdvvknnsekksenmnntfyccelccnpacagcy (서열번호 _; 참조 GenBank® Accession No. P01559(gi: 123711)를 갖는다. 프리 서열은 아미노산 1-19이다. 프로 서열은 아미노산 20-54이다. 성숙형 단백질은 55-72이다. E. coli ST-1B (ST-H) 단백질의 미성숙형(프리 및 프로 부위 포함함)은 서열: mkksilfiflsvlsfspfaqdakpvesskekitleskkcniakksnksgpesmnssnyccelccnpactgcy(서열번호 _; 참조 GenBank® Accession No. P07965(gi: 3915589)를 갖는다. Y. 엔테로콜리티카 ST 단백질의 미성숙형은(프리 및 프로 부위 포함함) 서열: mkkivfvlvlmlssfgafgqetvsgqfsdalstpitaevykqacdpplppaevssdwdccdvccnpacagc (서열번호 _; 참조 GenBank® Accession No.S25659 (gi: 282047)을 같는다.
본 발명의 펩티드는, 박테리아 ST 펩티드와 유사하게, 6개의 Cys 잔기를 가진다. 상기 6개의 Cys는 성숙 및 활성형의 펩티드에서 3개의 이황화 결합을 형성한다. 6개의 Cys를 상기 펩티드의 아미노 말단에서 카르복시 말단으로 A, B, C, D, E 및 F인 것으로 확인하면, 이황화 결합은 다음과 같이 형성된다: A-D, B- E, 및 C-F. 상기 결합의 형성은 GC-C 수용체 결합성에 매우 중요할 것으로 여겨진다. 본 발명의 특정 펩티드는 잠재력있는 기능성 키모트립신 절단 부위, 예컨대 Trp, Tyr 또는 Phe를 Cys B와 Cys D사이에 또는 Cys E와 Cys F 사이에 포함한다. 양쪽 키모트립신 절단 부위 중 어느 한 부위에서 절단되면, 상기 펩티드의 GC-C 수용체에 결합하는 능력이 감소 또는 없어진다.
체내에서, 키모트립신의 비활성 형태인 키모트립시노겐은 췌장에서 생산된다. 상기 비활성의 효소가 소장에 도착하면, 두개의 디-펩티드가 탈착되어 활성의 키모트립신으로 전환된다. 활성의 키모트립신은 펩티드 결합을 Trp, Tyr 또는 Phe의 카르복시 말단부에서 자를 수 있는 잠재력을 가지고 있다. 장관내부에 활성 키모트립신이 존재하게 되면 적절하게 위치된 기능적 키모트립신 절단 부위를 갖는 본 발명의 특정 펩티드는 절단되게 된다. 키모트립신 절단은, 적절하게 위치된 기능적 키모트립신 절단 부위를 갖는 본 발명의 펩티드를, 장관을 통하여 통과하는 펩티드로서의 작용을 완화시킬 것으로 예측된다.
키모트립신처럼 트립시노겐은 췌장에서 생성되는 세린 프로테아제이며, 소화관 내에 존재한다. 활성 형태인, 트립신은 Lys 또는 Arg을 가지고 있는 펩티드를 자를 것이다. 장관내에 활성 트립신의 존재는, 적절하게 위치된 기능적 트립신 절단 부위를 가진 본 발명의 특정 펩티드의 절단을 유발한다. 키모트립신 절단은, 적절하게 위치된 기능적 트립신 절단 부위를 갖는 본 발명의 펩티드를 장관을 통하여 통과하는 펩티드로서의 작용을 완화시킬 것으로 예측된다.
IBS를 포함한 다수의 위장병은, 복부 통증과 내장 통증과 관련되어 있다. 본 발명의 특정 펩티드는 기능성 키모트립신 절단 부위를 형성하는 Trp, Tyr 또는 Phe, 또는 기능성 트립신 절단 부위를 형성하는 Lys 또는 Arg 바로 다음의 카르복시 말단 서열 AspPhe와 같은 진통성 태그(tag) 또는 항통각성 태그를 포함한다. 장관의 키모트립신은, Trp, Phe 또는 Tyr 잔기의 카르복시 말단 펩티드를 잠재적으로 절단할 수 있으며, 디펩티드 AspPhe를 해리시킨다. 상기 디펩티드는 동물 모델에서 진통 활성이 있는 것으로 확인되었다(Abdikkahi et al. 2001, Fundam Clin Pharmacol 15: 117-23; Nikfar et al 1997, 29 :583-6 ;Edmundson et al 1998, Clin Pharmacol Ther 63: 580-93). 상기한 방식으로, 상기 펩티드는 통증과 염증을 모두 치료할 수 있다. 엔도모르핀-1, 엔도모르핀-2, 노시스테틴, 달라긴, 루프론 및 물질 P를 포함한 그외 진통성 펩티드는 상기 펩티드의 (기능적 절단 부위 이후에) 카르복시 말단에 존재할 수 있다.
다수의 유용한 펩티드는 코어 서열(core sequence)에 기초한다: Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. 상기 펩티드를 불활성시킬 수 있는 잠재적인 기능적 키모트립신 절단 부위를 가진 변형체를 제조하기 위하여, Leu(밑줄로 표시됨) 또는 Thr(밑줄로 표시됨)은 Trp, Phe 또는 Tyr으로 교체하거나, 또는 Leu과 Thr 둘다 (독립적으로) Trp, Phe 또는 Tyr로 교체할 수 있다. 진통성 디펩티드를 가진 변형체를 제조하기 위하여, 코어 서열 다음에 AspPhe이 온다. 코어 서열에서 카르복시 말단의 Tyr은, Asp Phe 디펩티드가 소화관에서 키모트립신에 의해 해리되도록 한다. 상기 코어 서열은 선택적으로 Asn Ser Ser Asn Tyr 또는 Asn에 의해 상위에 위치될 수 있다.
따라서, 코어 서열을 근간으로한 유용한 변형체는 다음을 포함한다:
Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 4)
Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 5)
Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 6)
Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr (서열번호 _)
Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 3)
Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr Asp Phe (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 --)
Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 -)
Asn Ser Ser Asn Tyr Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Ser Ser Asn Tyr Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
Asn Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe (서열번호 _)
일부 경우에서, 본 발명의 펩티드는 아미노 말단의 리더 서열을 함유하는 프리프로 단백질로서 생산된다: mkksilfiflsvlsfspfaqdakpvesskekitleskkcniakksnksgpesmn. 상기 펩티드는 박테리아 세포, 예컨대 E. coli에 의해 생산되는 경우, 상위의 리더 서열은 절단될 것이고, 성숙형 펩티드는 박테리아 세포로부터 효율적으로 분비될 것이다. 미국 특허 5,395,490에 벡터, 발현 시스템, 박테리아 세포에서 ST 펩티드이 효율적인 생산 방법 및 성숙형 ST 펩티드를 효과적으로 분비시키기 위한 방법이 개시되어 있다. 미국 특허 5,395,490에 개시된 상기 벡터, 발현 시스템 및 방법은 본 발명의 ST 펩티드 및 변형 ST 펩티드를 생산하는데 사용할 수 있다.
변형 펩타이트
본 발명은 SEQ ID NO _ 내지 _에 비하여 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개(일부 실시예들에서는 5 미만, 3 미만, 2이하 개)의 아미노산 치환체를 포함할 수 있는 변형 펩티드를 포함한다. 상기 치환체(들)는 보존적이거나 비보존적일 수 있다. 천연 아미노산은 임의의 아미노산의 D-이성체, 비천연 아미노산, 천연 및 비천연성 아미노산 유사체, 또는 그외 기로 치환될 수 있다. 보존적 아미노산 치환으로, 유사하게 작용하는 아미노산 또는 전하, 극성 또는 소수성이 유사한 아미노산으로의 아미노산 변이가 발생된다. 동일한 위치에서의 보존적 아미노산의 치환도 펩티드의 활성을 감소시킬 수 있다. 보본적 치환은 비천연 아미노산에 대한 천연 아미노산의 치환일 수 있다. 천연 아미노산에서 아미노산 치환은 표 2에 나타낸다.
아미노산 코드 치환
알라닌 Ala Gly, Cys, Ser
알기닌 Arg Lys, His
아스파라긴 Asn Asp, Glu, Gln
아스파틱산 Asp Asn, Glu, Gln
시스테인 Cys Met, Thr, Ser
글루타민 Gln Asn, Glu, Asp
글루타믹산 Glu Asp, Asn, Gln
글리신 Gly Ala
히스티딘 His Lys, Arg
이소루신 Ile Val, Leu, Met
루신 Leu Val, Ile, Met
라이신 Lys Arg, His
메티오닌 Met Ile, Leu, Val
페닐알라닌 Phe Tyr, His, Trp
프롤린 Pro
세린 Ser Thr, Cys, Ala
트레오닌 Thr Ser, Met, Val
트립토판 Trp Phe, Tyr
티로신 Tyr Phe, His
발린 Val Leu, Ile, Met
일부 조건에서는, 장의 GC-C 수용체에 결합하여 활성화시키나 비변형체 펩티드에 비해 활성이 낮은, 변형 펩티드를 이용하여 환자를 치료하는 것이 적합할 수 있다. 상기 감소된 활성은 수용체에 대한 친화성 감소, 또는 수용체의 결합 후 수용체를 활성화시키는 능력 감소, 또는 펩티드 안정성 감소를 발생시킬 수 있다.
펩티드 제조
유용한 펩티드는 이에 한정되진 않으나 E. coli를 포함한 박테리아나, 또는 그외 현존하는 펩티드 또는 단백질 생산 시스템(예, 바실러스 섭틸리스, 초파리 Sf9 세포를 이용한 베큘로바이러스 발현 시스템, 효모 또는 필라멘트형 진균 발현 시스템, 포유류 세포 발현 시스템)으로 생산할 수 있으며, 또는 화학적으로 합성할 수 있다.
펩티드 또는 변형 펩티드가 박테리아, 예컨대 E. coli에서 생산되는 경우, 상기 펩티드를 코딩하는 핵산 분자는 성숙형 펩티드가 세포에서 분비되도록 허용하는 리더 서열을 코딩하는 것이 또한 바람직할 것이다. 따라서, 펩티드를 코딩하는 서열은 프리 서열 및 프로 서열, 예컨대 천연 박테리아 ST 펩티드를 포함할 수 있다. 분비된, 성숙형 펩티드는 배양 배지로부터 정제할 수 있다.
본 발명의 펩티드를 코딩하는 서열은 박테리아 세포내에 상기 핵산 분자를 전달하고 유지시킬 수 있는 벡터내로 삽입되는 것이 바람직하다. DNA 분자는 자율 복제성 벡터(적합한 벡터로, 예컨대 pGEM3Z 및 pcDNA3, 및 이들의 유도체를 포함함)로 삽입될 수 있다. 상기 벡터의 핵산은 박테리오파지 람다 또는 M13, 및 이의 유도체와 같은 박테리아 DNA 또는 박테리오파지 DNA일 수 있다. 본 발명의 핵산을 함유하는 벡터의 구축 후, 박테리아와 같은 숙주 세포에 형질전환이 실시된다. 적합한 박테리아계 숙주로는, E. coli, 바실러스 섭틸리스, 슈도모나스, 살모넬라를 포함하나, 이에 한정되진 않는다. 또한 상기 유전자 구조체는 코딩 핵산 분자 뿐만 아니라, 프로모터 및 조절 서열과 같은 발현을 가능하게 하는 요소를 또한 포함한다. 상기 발현 벡터는 프로모터, 인핸서, 오퍼레이터 및 억제 서열과 같은, 전사 개시를 조절하는 전사 조절 서열을 포함할 수 있다. 다양한 전사 조절 서열들이 당업계에 알려져 있다. 상기 발현 벡터는 또한 번역 조절 서열(예, 비번역성 5' 서열, 비번역성 3' 서열 또는 내부 리보솜 도입 부위)를 포함할 수 있다. 상기 벡터는 자율적으로 복제할 수 있거나, 또는 숙주 DNA내로 삽입되어 펩티드가 생산되는 동안 안정성을 확보할 수 있다.
본 발명의 펩티드를 포함하는 단백질 코딩 서열은, 정제 용이성을 위해, 폴리펩티드 친화성 태그, 예컨대 글루타티온 S-트랜스퍼레이즈(GST), 말토스 E 결합 단백질, 단백질 A, FLAG 태그, 헥사-히스티딘, myc 태그 또는 인플루엔자 HA 태그를 코딩하는 핵산에 융합시킬 수 있다. 상기 친화성 태그 또는 리포터의 융합은, 친화성 태그를 코딩하는 유전자의 리딩 플래임(reading frame)을 목적한 펩티드의 리딩 플래임에 접합시켜, 번역의 융합이 이루어진다. 융합 유전자의 발현시 목적 펩티드와 친화성 태그 모두를 함유하는 단일 폴리펩티드가 번역된다. 친화성 태그를 활용하는 경우에, 프로테이즈 인식 부위를 코딩하는 DNA 서열을 친화성 태그의 리딩 플래임과 목적 펩티드 사이에 융합시킬 수 있다.
본 발명의 미성숙 또는 성숙 펩티드와 변형체를 박테리아 이외의 단백질 발현 시스템에서 생산하기에 적합한 유전자 구조체 및 방법과, 당업자에게 잘 알려진 방법은, 생물 시스템에서 펩티드를 생산하기 위해 사용될 수 있다.
성숙 펩티드와 이의 변형체는 자동 펩티드 합성기를 이용한 고체상 방법에 의해 합성될 수 있다. 예컨대, 펩티드는 이중 커플링 프로그램을 이용하여 Cyc(4-CH2Bxl)-OCH2-4-(옥시메틸)-페닐아세트아미도메틸 수지상에 합성될 수 있다. 보호기는 정확한 이황화 결합 양상을 형성하기 위해 적절하게 사용되어야 한다. 예컨대, 다음 보호기를 사용할 수 있다: t-부틸옥시카르보닐(알파-아미노 기); 아세트아미도메틸(Cys B와 E의 티올 기); 4-메틸벤질(Cys C와 F의 티올기); 벤질(존재하는 경우, 글루타민산의 y-카르복시 및 트레오닌의 하이드록시 기); 및 브로모벤질(존재하는 경우, 티로신의 페놀릭 기). 커플링은 t-부톡실카르보닐아미노 산 또는 하이드록시벤조트리아졸 에스테르(알스파라긴 또는 글루타민 잔기의 경우)의 대칭 무수물로 이룰수 있으며, 상기 펩티드는 하이드로겐 플루오라이드, 디메틸 설파이드, 아니졸 및 p-티오크레졸을 8/1/1/0.5 비율(v/v/v/w) 내에서 0 ℃에서 60 분간 탈보호화되고 고체 지지체로부터 탈착된다. 감압에 의해 하이드로겐 플루오라이드 및 디메일 설파이드를 제거하고, 이후 에틸 에테르 및 에틸 아세테이트를 이용한 추출에 의해 아니졸 및 p-티오크레졸을 제거한 다음, 조 펩티드(crude peptide)는 pH 8.0의 0.5 M 소듐 포스페이트 완충액과 N,N-디메틸포름아미드가 1:1 v/v 비율로 포함된 혼합물로 추출한다. Cys 잔기 B와 E에서 이황화 결합은 디메틸 설폭사이드를 이용하여 형성한다(Tam et al.(1991) J. Ana. Chem. Soc. 113: 6657-62). 결과물 펩티드는 역상 크로마토그래피로 정제한다. Cys 잔기 C와 F 간의 이황화 결합은 수중 50% 아세트산에 상기 펩티드를 용해시킴으로써 형성시킨다. 빙초산(glacial acetic acid)중의 포화 요오드 용액을 첨가한다(용액 100 ml당 요오드 용액 1 ml). 실온에서 2일간 봉합한 유리 용기내에 둔 다음, 상기 용액을 탈이온수로 5배 희석하고, 무반응성 요오드를 제거하기 위해 에틸 에테르로 추출한다. 회전식 증발로 남아있는 에틸 에테르를 제거한 다음, 조 펩티드 용액을 동결 건조하고, 연속 역위 크로마토그래피로 정제한다.
또한, 펩티드는 기존의 FMOC 보호(즉, DCC-HOBt로 커플링 및 DMF 중의 피페리딘을 이용한 탈보호)를 이용하여 고상 합성을 포함한 그외 다수 방법으로 합성할 수 있다. Cys 티올 기는 트리틸 보호될 수 있다. TFA를 처리하여 펩티드의 최종 탈보호와 고상 수지로부터 펩티드를 분리할 수 있다. 많은 경우들에서, 공기 산화는 적절한 이황화 결합을 형성하는데 충분하다.
장의 GC -C 수용체 결합 분석
장의 GC-C 수용체에 결합하는 펩티드와 그외 제제의 능력은 하기한 바와 같이 테스트될 수 있다. 인간 대장암 세포주 T84(American Type Culture Collection (Bethesda, Md.))를, 함스 F12 배지(Ham's F12 medium)와 둘베코스 변형 이글스 배지(Dulbecco's modified Eagle's medium (DMEM))의 1:1 혼합물과 5 % 소태아 혈청이 첨가된 배지로 24웰 배양 플레이트에서 컨플루언시로 생육시켰다. 본 분석에 사용하는 세포는 54-60로 계대배양하였다. 간략하게 설명하면, 24웰 플레이트내에 T84 세포 단층을 1 ml의 결합 완충액(0.05% 소 혈청 알부민 및 25 mM HEPES가 함유된 DMEM, pH 7.2)으로 2회 세척하고, 이후 방사 표지된 성숙형 E. coli ST 펩티드와 여러가지 농도의 테스트 물질 존재하에 37 ℃에서 30분간 배양하였다. 이후 세포는 DMEM 1 ml로 4회 세척하고, 1N NaOH 0.5 ml/웰로 용해하였다. 용해시킨 물질의 방사능 수치를 표준 방법을 이용하여 결정하였다.
도 1은 서열번호 4의 재조합 펩티드 및 서열번호 5의 재조합 펩티드의 LCMS 분석 결과이다.
도 lb 및 1c는 서열 3의 합성 펩티드와 블랭크의 LCMS 분석 결과이다.
도 2는 서열번호 4의 합성 펩티드, 서열번호 5의 합성 펩티드 및 두 종의 상이한 서열번호 3의 합성 펩티드의 장 GC-C 수용체 활성 결과이다.
도 3a는 급성 뮤라인 위장 통과 모델에서의 서열번호 4의 재조합 펩티드 및 Zelnorm®의 효과를 나타낸 것이다.
도 3b는 급성 뮤라인 위장 통과 모델에서의 서열번호 3의 합성 펩티드 및 Zelnorm®의 효과를 나타낸 것이다.
도 4a 및 4b는 급성 뮤라인 위장 통과 모델에서의 서열번호 5, 3 및 4의 펩티드 효과를 나타낸 것이다.
도 4c는 만성 뮤라인 위장 통과 모델에서의 서열번호 3의 펩티드 효과를 나타낸 것이다.
도 5a는 젖먹이 마우스의 장 배출 모델에서의 서열번호 4의 펩티드 및 Zelnorm®의 효과를 나타낸 것이다.
도 5b는 마우스의 장 배출 모델에서의 서열번호 3의 펩티드 및 Zelnorm®의 효과를 나타낸 것이다.
도 6a 및 6b는 마우스의 장 배출 모델에서의 서열번호 4, 3 및 5의 펩티드 효과를 나타낸 것이다.
도 7은 TNBS 장 팽만 모델에서 서열번호 3의 활성을 분석한 실험 결과이다.
도 8a 및 8b는 PBQ 비틀기(writhing) 분석에서의 서열번호 5와 서열번호 3의 여러가지 투여량에 따른 효과를 나타낸 것이다.
도 9는 경쟁적 방사성리간드 결합 분석에서 서열번호 3을 이용한 Kd 결정 분석 결과이다.
도 lOa 및 lOb는 ELISA 분석과 LCMS로 검출한 것으로서, IV 및 경구 투여한 서열번호 3의 생체이용성 결과이다.
도 11은 서열번호 3의 서열을 가지는 펩티드의 결손 변이체들이다.
도 12는 서열번호 3의 서열을 가지는 펩티드의 삽입 변이체들이다.
실시예 1: ST 펩티드 변형체 천연형 ST 펩티드 1a의 제조: 재조합 ST 펩티드 변형체 천연형 ST 펩티드의 제조
서열 Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 5)의 ST 펩티드 변형체는 재조합으로 생산하였고 동물 모델에서 테스트하였다. 천연형 ST 펩티드를 갖는 펩티드 역시 재조하였다(서열번호 4).
서열번호 5와 서열번호 4 펩티드는 아래와 같이 제조된 벡터를 이용하여 프리프로단백질로 생산하였다. 열 안정한 엔테로톡신 프리-프로 서열을 코딩하는 서열을 올리고뉴클레오티드 M03514(5'CACACCATATGAAGAAATCAATATTATTTATTTTTCTTTCTG-3' (SEG ID NO:))와 올리고뉴클레오티드 M03515 (5'- CACACCTCGAGTTAGGTCTCCATGCTTTCAGGACCACTTTTATTAC-3'(SEQ ID NO :))를 이용하여 pGK51/pGSK51 (ATCC 67728)로부터 증폭하였다. 증폭 산물은 NdeI/XhoI로 절단하고 NdeI/XhoI로 개환한 T7 발현 벡터, pET26b(+)(Novagen)에 삽입하여 플라스미드 MB3976를 제조하였다. 프리-프로 단백질을 코딩하는 부분을 서열분석하여, 그 결과 아미노산 서열, mkksilfiflsvlsfspfaqdakpagsskekitleskkcnivkk s n k s g pesm(SEQ ID NO:)을 코드화하고 있음을 확인하였고, 상기 서열은 열 안정성 엔테로톡신 a2 전구체의 아미노산 서열(sta2; mkksilflflsvlsfspfaqdakpagsskekitleskkcnivkknnesspesm(SEQ ID NO:) ;GenBank'Accession No. Q47185, GI: 3913876)과는 C-말단 근처의 3곳(밑줄 및 굵은 체로 표시됨)에서 차이가 있었다. 프리-프로 서열이 있는 발현 벡터를 제조하기 위해, 각 ST 펩티드 변이체 또는 천연형 ST 펩티드를 코딩하는 상보적인 올리고들을 어닐링하고, MB3976 발현 벡터로 클로닝하였다. 프리-프로 서열의 하위에 융합된 아미노산 서열 NSSNYCCELCCNPACTGCY(SEQ ID NO:)을 포함하는 MB3984(프리프로 단백질로서 서열번호 4 전장 천연형 ST 펩티드를 코딩함)를 제조하기 위해, MB 3976는 Bsal/XhoI로 절단하고 어닐링한 올리고 M03621 (5'-GCATGAATAGTAGCAATTACTGCTGTGAATTGTGTTGTAATCCTGCTTGTACCGGGTGCTATTAATAAC-3'(SEQ ID NO:_)와 M03622(5'-TCGAGTTATTAATAGCACCCGGTACAAGCAGGATTACAACACAATTCACAG CAGTAATTGCTACTATTC-3'(SEQ ID NO:_)에 연결하였다. 프리-프로 서열의 하위에 아미노산 서열 NSSNYCCEYCCNPACTGCY이 융합된 MB3985(프리프로 단백질로서 서열번호 5를 코딩함)를 제조하기 위하여, MB 3976를 BsaI/XhoI로 절단하고 어닐링한 올리고 M03529(5'-GCATGAATAGTAGCAATTACTGCTGTGAATATTGTTGTAATCCTGCTTGTACCGGGTGCTATTAATAAC-3'(SEQ ID NO:_))와 M03530(5'-TCGAGTTATTAATAGCACCCGGTACAAGCAGGATTACAACAATATTCACAGC AGTAATTGCTACTATTC-3'(SEQ ID NO : _))에 연결하였다.
서열번호 5 펩티드와 서열번호 4 펩타이들를 하기와 같이 제조하였다. 발현 벡터를 E. coli bacterial host BL21λDE3(Invitrogen)에 형질전환하였다. 단일 콜로니를 L 액체 배지 + 25 mg/L 카나마이신에 접종하여 30 ℃에서 하룻밤 교반 배양하였다. 배양물을 3.2 L의 배치 배지(글루코스 25 g/L, 카세이아미노산 5 g/L, 효모 추출물 5 g/L, KH2PO4 13.3 g/L, (NH4)2HP04 4 g/L, MgS04-7H20 1.2 g/L, 시트르산 1.7 g/L, EDTA 8.4 mg/L, CoCl2-6H20 2.5 mg/L, MnCl2-4H20 15 mg/L, CuCl2-4H20 1.5 mg/L, H3BO3 3 mg/L, Na2Mo04-2H20 2.5 mg/L, Zn 아세테이트-2H20 13 mg/L, 페릭 사이트레이트 100 mg/L, 카나마이신 25mg/L, 항기포제(Antifoam) DF204 1 ㎖/L)에 첨가하였고, 다음 조건으로 발효하였다: pH 6.7 - 단지 염기(28% NH40H)만을 이용한 대조군, 30℃, 통기: 분당 5 L. (용존 산소(DO) 수치를 모니터링한 것을 토대로)배치 글루코스가 소진된 후, 피드 배지(글루코스 700 g/L, 카세이아미노산 10 g/L, 효모 추출물 10 g/L, MgS04-7H20 4 g/L, EDTA 13 mg/L, CoCl2-6H20 4 mg/L, MnCl2-4H20 23.5 mg/L, CuCl2-4H20 2.5 mg/L, H3BO3 5 mg/L, Na2Mo04-2H20 4 mg/L, Zn 아세테이트-2H20 16 mg/L, 페릭 사이트레이트 40 mg/L, 항기포제(Antifoam) DF204 1 ㎖/L) 1.5 L를 조절된 공급 속도로 첨가하고 20 % DO를 유지시켰다. IPTG를 공급 개시 2 시간 후 0.2 mM로 첨가하였다. 총 운행 시간은 약 40-45 시간(공급물이 고갈될때까지)이었다.
세포는 10 분간 5,000으로 원심분리하여 수집하였다. 세포 펠렛은 버리고 상등액을 50 Kd 초미세여과 단위를 통과시켰다. 50 Kd 여과물(0.6 L)를 110 ml Q- 세파로스 패스트 컬럼(AmershamPharmacia, 20 mM Tris-HCl (pH 7.5)로 평형화됨)에 유속 400 ml/hour로 주입하였다. 상기 컬럼은 6 부피배의 20 mM Tris-HCl pH 7.5로 세척하고, 단백질은 50 mM 아세트산으로 용출시켜 50 ml씩 분취하였다. ST 펩티드 변형체 또는 천연형 ST 펩티드가 함유된 분획들은 모우고, 회전 증발기로 용매를 제거하였다. 건조한 단백질은 8% 아세트산 10 ml, 0.1% 트리플루오로아세트산(TFA)에 재현탁하고 유속 20 ml/분으로 Varian Polaris C18-A 컬럼(250 X 21.2 mm 10 ㎛, 동일 완충액으로 평형화됨)에 주입하였다. 상기 컬럼은 8% 메탄올 100 ml과 0.1% TFA로 세척하고 24 내지 48%의 0.1% TFA가 함유된 메탄올 구배농도(300 ml)로 전개하였고, 5 ml 씩 분취하였다. 펩티드를 함유한 분획을 모우고, 용매는 회전식 증발기로 제거하였다. 펩티드는 0.1% TFA에 용해하고 동결건조하였다.
서열번호 5 펩티드와 서열번호 4 펩티드 분획은 표준 LCMS 및 HPLC로 분석하였다. LCMS 분석으로, 서열번호 5가 서열번호 4(참조 도 la; 서열번호 5 펩티드(패널 B)는 서열번호 4 (패널 A)에 비해 피크 수가 적다)에 비해 더 동질적임을 확인하였다.
1b: 합성 ST 펩티드 변이체 천연형 ST 펩티드의 제조
펩티드는 상업적인 펩티드 합성 회사를 통하여 화학적으로 합성하였다. 다양한 수율의 펩티드가 화학 합성 효율에 따라 수득되었다. 따라서, 4종의 펩티드들의 수율이 낮은 순서는 다음과 같다: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 3), 10-20% 수율; Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 6); Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 5); Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr(서열번호 4), < 5% 수율. 따라서 펩티드에 도입된 특이 아미노산 변화로 개선된 제조 특성을 형성시킬 수 있다.
도 1b는 합성한 서열번호 3의 총 이온 크로마토그래피 프로파일이다. 도 lc는 대조군 블랭크 샘플의 총 이온 크로마토그래피 프로파일이다. 서열번호 3 샘플에서 주 피크 하나가 존재하나 대조군 샘플에는 존재하지 않는다. 정량분석으로 서열번호 3은 > 98% 순도인 것으로 보인다.
실시예 2: ST 펩티드 변이체 ST 펩티드에 의한 장내 GC -Cㅜ 수용체의 활성
장의 GC-C 수용체를 활성화시키는 서열번호 5, 서열번호 4, 및 서열번호 3의 능력은 T84 인간 대장암 세포주(American Type Culture Collection (Bethesda, Md.))를 이용한 분석으로 평가하였다. 상기 분석으로, 세포는 함스 F12 배지와 둘베크코스 변형 이글스 배지(DMEM)이 1:1로 혼합되어 있으며 5% 우태아 칼프 혈청이 함유된 배질로 24웰 플레이트에서 컨플루언시로 배양하였고, 54-60 계대 배양한 것을 사용하였다.
간략하기로는, 24웰 플레이트내 T84 세포의 단층을 1 ml웰 DMEM으로 2회 세척하고, 1 mM 이소부틸메틸잔틴(IBMX), 시클릭 뉴클레오타이드 포스포디에스테레이즈 저해제가 함유된 0.45 ml DMEM으로 10분간 37 ℃에서 배양하였다. 테스트 펩티드(50 ㎕)를 첨가한 후 37 ℃에서 30분간 배양하였다. 상기 배지는 흡입하여 제거하고, 차가운 0.1 N HCl 0.5 ml을 첨가하여 반응을 종결시켰다. 상기 샘플은 20분 간 얼음에 둔 다음 열총 또는 진공 원심분리를 이용하여 증발하여 건조시켰다. 건조된 샘플은 Cayman Chemical Cyclic GMP EIA kit (Cayman Chemical, Ann Arbor, MI)에 제공되는 인산 완충액 0.5 ml로 재현탁하였다. 시클릭 GMP는 Cayman Chemical Cyclic GMP EIA kit에서 제시한 공정에 따라 EIA로 측정하였다.
도 2는 GC-C 수용체 활성 분석에서 화학 합성 펩티드의 활성을 나타낸 것이다. 분석에서, 서열번호 4와 다른 두개의 펩티드 서열번호 3(서열번호 3(a) 및 서열번호 3(b), 두 가지의 다른 방법으로 합성함)는 서열번호 4와 비교되는 활성을 나타내었다. 서열번호 5와 서열번호 4 펩티드는 서열번호 3(b)와 동일한 방식으로 화학 합성하였다.
실시예 3: 서열번호 5와 서열번호 4는 마우스에서 장 통과를 증가시킨다.
상기 펩티드가 위장 통과 속도를 증가시키는지 여부를 결정하기 위하여, 펩티드와 대조군을 쥐과 동물의 위장 통과(GIT) 분석으로 테스트하였다(Moon et al. Infection and Imrnunity 25:127, 1979). 본 분석에서, 위장관에서 쉽게 가시화시킬 수 있는 차콜(charcoal)을 테스트 화합물 투여 후 마우스에 투여하였다. 차콜의 이동 거리를 측정하였고, 대장 총 길이의 퍼센트로 나타내었다.
마우스는 펩티드 또는 대조군 완충액 처리 전에 12-16시간 동안 금식시켰으며 물은 자유롭게 섭취하도록 하였다. 펩티드는 5% 활성탄(Aldrich 242276-250G)을 경구 투약하기 7분 전에 완충액(20 mM Tris pH 7.5)내 펩티드를 1 ㎍/kg - 1 mg/kg으로 경구 투여하였다. 대조군 마우스에는 활성탄 투약 전에 단지 완충액만을 투여하였다. 15분 후, 마우스를 취사하고, 위에서 맹장에 이르는 장을 적출하 였다. 장의 총 길이와 위에서 차콜 바로 앞 이동 거리를 각 동물 별로 측정하였고, 그 결과는 차콜의 장 이동 총 거리 %로 나타내었다. 모든 결과는 10 마리 마우스의 평균 + 표준편차로 기재하였다. 펩티드를 처리한 마우스와 비히클만을 처이한 마우스 간의 차콜 이동 거리의 비교는 Student's t test로 실시하였고, 통계적 유의차는 P < 0.05이었다. P 값은 양측(two-sided) T-테스트로 계산하여, 비동등한 가변치를 추정하였다.
도 3a, b에 보여진 바와 같이, 천연형 ST 펩티드(서열번호 4, (Sigma-Aldrich, St Louis, MO ; 0.1 mg/kg)), 합성한 서열번호 3 및 세로토닌 수용체 5HT4에 대한 작용제로 IBS에서 승인받은 약물 Zelnorm®(0.1 mg/kg)는 상기 모델에서 위장 통과 속도를 증가시켰다. 도 4a는 장 통과 속도를 재조합 합성된 서열번호 4 또는 서열번호 5 중 어느 하나의 투여량 증가와 더불어 증가시킴을 입증한 연구 결과이다. 도 4b는 화학 합성한 서열번호 4 또는 서열번호 3 펩티드 모두 트리스 완충액 단독으로 사용하거나 또는 Zelnorm®와 동일 투여량에 비하여 장 통과 속도가 증가시킴을 입증하는 연구 결과이다.
서열번호 3이 장기적인 투약 치료요법에 효과적인지를 결정하기 위해 동일한 실험을 실시하였다. 간략하게는, 8주령의 CD1 암컷 마우스에 하루에 1회 5일간 서열번호 3(0.06mg/kg 또는 0.25mg/kg, 20mM Tris pH 7.5) 또는 비히클(20mM Tris pH 7.5)만 단독으로 경구 투여하였다. 5일째, GIT 분석을 10% 차콜 용액을 200 ㎕으로 투여하는 것을 제외하고는 상기와 동일하게 수행하였다. 도 4c는 화학 합성한 서열번호 3 또는 Zelnorm® 모두 장기적인 투약시(5일간) 마우스 위장 운동에 효과적임을 입증하는 연구 결과이다. 상기 결과는 급성 투약시(1일)와 나란히 나타내었다.
실시예 4: 서열번호 5 펩티드와 서열번호 4 펩티드는 젖먹이 마우스에서 장내 분비를 증가시킨다( SuMi 분석)
서열번호 4와 서열번호 5를, 장 배설의 적먹이 마우스 모델을 이용하여 장내 분비를 증가시키는 능력을 테스트하였다. 상기 모델에서, 테스트 화합물은 7-9일령의 젖먹이 마우스에 투여하였다. 동물은 취사하고, 위에서 맹장에 이르는 위장관을 절개하였다("장(gut)"). 장 뿐만 아니라 나머지 부분("시체(carcass)")들의 무게를 측정하고, 나머지 부분에 대한 장 비율을 계산하였다. 상기 배율이 0.09 보다 높으면, 테스트 화합물이 장내 분비를 증가시키는 것으로 결론지을 수 있다. 도 5a는 상기 모델에서 천연형 ST 펩티드(서열번호 4)에 대한 투약 반응 곡선이다. 도 5b는 상기 모델에서의 서열번호 3 펩티드에 대한 투약 반응 곡선이다. 이러한 결과는 천연형 ST 펩티드(TDT, Inc에서 구입함. West Chester, PA)와 MD- 1100 펩티드가 장내 분비를 증가시킴을 보이는 것이다. 또한 Zelnorm®의 효과를 연구하였다. 도 5에서 확인된 바와 같이, Zelnorm® 0.2 mg/kg으로 투여시 상기 모델에서 장내 분비를 증가시키지 못하였다. 도 6a는 상기 재조합 서열번호 4 펩티드와 재조합 서열번호 5 펩타이에 대한 투약 반응 곡선이다. 도 6a로 알 수 있는 바와같이, 두 펩티드 모두 상기 모델에서 장내 분비를 증가시켰다. 도 6b도 화학 합성한 서열번호 5, 서열번호 3 및 서열번호 4 뿐만 아니라 천연형 ST 펩티드(Sigma-Aldrich로부터 구입함, St Louis, MO)에 대해 유사한 투약 반응 곡선을 나타낸다.
대장 통각과민 동물 모델
결장직장 팽창에 대한 과민증은 IBS 환자에서 일반적인 것이며, 통증의 주된 원인일 수 있다. 팽창에 대한 내장 통각과민(visceral hyperalgesia)의 염증성 또는 무염증성 동물 모델이 IBS에서 내장 통증에 대한 화합물의 효과를 조사하기 위해 개발되고 있다.
I. 트리니트로벤젠설폰산 ( TNBS )- 유발성 직장 이질통 모델
수컷 Wistar 랫(220-250 g)에 아세프로마진(acepromazine) 0.5 mg/kg을 복막내(IP) 주사하고, 케타민 100 mg/kg을 근육내 주사하여 마취시켰다. 니크롬 선 전극 쌍(길이 60 cm, 직경 80 ㎛)을 복부의 줄무늬근에 흰 선의 2 cm 측면으로 이식하였다. 나머지 전극 한쪽 끝은 목 뒷 쪽으로 밖으로 내고, 플라스틱 관에 의해 피부 접촉을 보호하였다. 근전도(Electromyographic)(EMG) 기록은 외과적 처치 후 5일 경과시 시작하였다. 복부 줄무늬근의 전기적 활성은 단시간 상수(0.03초)를 이용하여 기 뇌파계(electroencephalograph) 장치(Mini VIII, Alvar, Paris, France)로 기록하여 낮은 빈도 신호는 제거하였다(< 3 Hz).
외과적 이식 10일 후, 트리니트로벤젠설폰산(TNBS)를 투여하여 직장 염증을 유발하였다. 개시된 바에 따라(Morteau et al. 1994 Dig Dis Sci 39: 1239), 디에틸-에테르에 의한 가벼운 마취하에 TNBS(50% 에탄올 0.3 ml내 80 mgkg-1)를 항문으 로부터 3 cm 삽입된 실리콘 고무 카테터를 통하여 직장내로 투여하였다. TNBS 투여 후, 랫은 결장직장 팽창(CRD)전 몇일간 운동성이 제한된 플라스틱 터널하에 두었다. 실험 화합물을, 직장으로 라텍스 콘돔으로 제조된 4 cm 길이의 풍선을 항문에서 1 cm로 삽입하는 것으로 수행되는 CRD 한시간 전에 투여하였다(Gue et al, 1997 Neurogastroenterol. Motil. 9: 271). 풍선은 색전절제술(embolectomy) 프로브(Fogarty)로부터 취득한 경질 카테터상에 고정하였다. 풍선이 접착된 카테터는 꼬리 기저(base)에 고정하였다. 풍선은 바로스타트(barostat)에 연결하고, 0에서 60 mmHg까지 15 mmHg 단계로 점차 팽창시키고, 팽창 각 단계는 5분간 지속시켰다. 직장 민감도의 평가는 EMG로 측정한 바와 같이, 이후 TNBS의 직장내 점적하기 전(1-2일) 및 3일전에 실시하였다.
복부 수축에 상응하는 스파이크 파열 수를 5분 간격으로 확인하였다. 복부 수축 횟수에 대한 통계적 분석과 투약-효과 상호작용에 대한 평가를 일원분산분석(one way analysis of variance (ANOVA))으로 수행하였고, 적합한 경우 사후 검정(post-hoc)(Student or Dunnett tests)과 ED50에 대한 회귀분석을 실시하였다.
도 7은 TNBS 결장직장 모델에서 분석한 서열번호 3 활성에 대한 실험 결과이다. 복부 반응에서 유의할만한 감소가 0.3 ㎍/kg 및 3 ㎍/kg 서열번호 3에서 관찰되었다. 이러한 결과는, 서열번호 3이 동물 모델에서 직장결장 팽창과 관련된 통증을 감소시킴을 입증하는 것이다.
II. 스트레스 유발성 과민 모델
수컷 Wistar 랫(200-250 g)에 TNBS 모델에서와 같이 니크롬선 전극을 외과적으로 이식하였다. 외과 이식 10일 후, 부분적 억제성 스트레스(PRS)를 윌리암스 등(Williams et al. 1988 Gastroenterology 64: 611)에 의해 제시된 바와 같이 2시간 동안 수행하였다. 간략하게 설명하면, 에틸-에테르로 약하게 마취한 상태에서, 어깨 앞 부분(foreshoulder), 팔 상부 및 흉부 몸통(thoracic trunk)을 제한하기 위해 종이 테입으로 감금된 형태로 감쌌으나, 신체 이동을 제한하진 않았다. 대조군인 허위성 스트레스 동물은 마취시켰으나 감싸진 않았다. PRS 기간 종료 30분 전에 상기 동물에 테스트 화합물 또는 비히클을 투여하였다. PRS 종료 후 30분 재니 1시간 후에, CRD 팽창 공정을 상기 TNBS 모델에서와 같이 15, 30, 45 및 60 mmHg 에서 바로스타트로 수행하였다. 파열 수의 통계학적 분석을 실시하고 TNBS에서와 같이 분석하였다.
페닐벤조퀴논 유발성 비틀기 모델( writhing model )
PBQ 유발성 비틀기 모델을 사용하여 본 발명의 펩티드 및 GC-C 수용체 작용제의 통증 조절 활성을 평가하였다. 본 모델은 Siegmund et al. (1957 Proc. Soc. Exp. Bio. Med. 95: 729-731)에 의해 개시되어 있다. 간략하게는, 테스트 화합물, 예컨대 펩티드, 모르핀 또는 비히클을 경구 투약한 후 1시간 경과시, 0.02% 페닐벤조퀴논(PBQ) 용액(12.5 mL/kg)을 마우스에 복막내 경로로 주사하였다. 스트레칭과 비틀기 횟수는 PBQ 주사 후 5 내지 10분째에 기록하였고, 35 내지 40분사이와 60 내지 65분 사이에 또한 측정하여 역학적 평가를 제공할 수 있었다. 상기 결과는 스트레치와 비틀기 횟수(평균 + 표준편차)로 나타내었고, 통각 역치의 가변 비율은 비히클 처리 군의 평균치로부터 계산하였다. 처리군과 대조군간의 모든 통계학적 유의차는 SigmaStat 소프트웨어를 이용한 일원분산분석(P < 0.05) 이후 잔차분산(residual variance)을 이용한 Dunnett's 테스트로 결정하였다.
도 8a과 8b는 PBQ 비틀기 분석에서 여러가지 투여량의 서열번호 5와 서열번호 3의 효과를 나타낸 것이다. 통증 조절 활성이 공지된 NSAID(비스테로이드계 항염증성 약물)인 인도메타신을 본 분석에 양성 대조군으로 사용하였다. 비틀기 모델에서 유의적인 감소는 비히클 대조군과 비교하였을때 서열번호 5(1 mg/kg dose)과 서열번호 3(2.5 mg/kg dose)에서 관찰되었다. 테스트한 가장 높은 투여약에서의 효율 감소가 또한 유사한 분석으로 테스트한 다른 다수의 화합물들(즉 5HT-3 길항제)에서 관찰되었다. 본 실험의 결과는, 서열번호 5와 서열번호 3 모두 내장 통증 모델에서 인도메타신의 중간 투여량에 비해 항통각 효과가 있음을 시사한다.
실시예 5: 서열번호의 3 Kd 결정
랫의 장 점막에서 발견된 GC-C 수용체에 대한 서열번호 3 친화성을 결정하기 위해, 경쟁적 결합 분석을 랫의 장 상피 세포를 이용하여 수행하였다. 랫의 소장의 상피세포는 Kessler et al. (J.Biol. Chem. 245: 5281-5288(1970))에 의해 개시된 바에 따라 수득하였다. 간략하게 설명하면, 동물을 취사하여 이들의 복강을 노출시켰다. 장은 얼음처럼 차가운 식염수 또는 PBS 300 ml로 헹구었다. 유문으로부터 10 cm 위치에서 측정한 소장 10 cm를 제거하고, 1 인치로 단편을 잘라내었다. 장 점막은 파라필름 조각과 P-1000 파이펫 팁간의 적당한 압력에 의해 밀어내었다. 장 상피세포는 2 ml의 PBS 상에 두어 5 ml의 파이펫으로 상하 파이펫팅하여 세포 현탁물을 제조하였다. 상기 현탁물내 단백질 농도는 브래드포드 방법(Anal. Biochem. 72: 248- 254 (1976))으로 측정하였다. .
경쟁적 결합 분석은 Giannella et al.(Am. J. Physiol. 245: G492-G498)의 방법을 기초로, [1251] 표지된 서열번호 4와 서열번호 3간에 수행하였다. 분석 혼합물은 포함한다:20 mM HEPES-KOH pH 7.0를 함유한 DME 0.5 ml, 0.9 mg의 상기 세포 현탁물, 21.4 fmol [125I]-서열번호 4(42.8 pM) 및 여러가지 농도의 경쟁자 서열번호 3 (0.01 내지 1000 nM). 혼합물은 실온에서 1시간동안 두었고, 혼합물을 GF/B 유리-섬유 필터(Whatman)에 적용하여 반응을 중지시켰다. 상기 필터는 얼음처럼 차가운 5 ml의 PBS로 세척하고, 방사능을 측정하였다. 도 9는 상기 분석에서 서열번호 3에 대한 Kd가 4.5 nm임을 나타내고 있다. % B/Bo는 차가운 경쟁자(Bo)가 없는 대조군 샘플에서 유지되는 방사능과 비교한 각 샘플(B)에서 측정한 방사능 비율 %이다. Giannella et al. (Anz. J. Physio. 245: G492-G498)은 동일 분석에서 천연형 ST 펩티드에 대한 Kd는 ~ 13 nm인 것으로 관찰하였다.
실시예 6: 서열번호 3의 약동학적 특성
서열번호 3의 약동학을 연구하기 위하여, 꼬리 동맥 주사를 통하여 정맥내로 또는 8주령의 CD1 마우스에 위관에 의한 경구로 서열번호 3을 투여함으로써 마우스에서 흡수성 실험을 실시하였다. 다양한 시기에 동물로부터 혈청을 수집하고, 경쟁적 효소 결합 면역흡착 분석법(enzyme-linked immunoabsorbent assay)(Oxoid, ST EIA kit, Cat# TD0700)을 이용하여 서열번호 3 존재를 테스트하였다. 상기 분석은 ST 펩티드에 대한 모노클로날 항체(Oxoid 키트에서 제공되는 항체)와 합성에 의해 제조된 서열번호 3을 활용한다. 도 10a는 ELISA 분석에 의해 검출된 바와 같이 정맥 및 경구 투여된 서열번호 3에 대한 흡수 데이터이다. 서열번호 3은 최소한으로 전신 흡수되는 것으로 보여지며, 생체 이용성은 < 2.2%이다.
유사한 생체이용성 실험을 ELISA가 아닌 LCMS를 이용한 서열번호 3 검출에 수행하였다. 먼저, 혈청 샘플을 노출된 마우스 및 대조군 마우스의 전 혈액으로부터 추출하고, SPE(solid phase extraction) 컬럼(Waters Oasis HLB 25mm column, 2.0 x 15 mm direct connect)의 선에 직접 10 ml을 주입하였고 추가적인 과정은 실시하지 않았다. SPE 컬럼상의 샘플은 5% 메탄올 및 95% dH2O 용액(2.1 mL/min, 1.0 분)으로 세척하고, 이후 SPE 컬럼에 분석용 컬럼(Waters Xterra MS C8 5mm IS column, 2.1 x 20mm)의 상위에 역류 패치 형태로 장착된 밸브를 이용하여 분석용 컬럼으로 주입하였다. 분석용 컬럼에서 역상 구배를 통하여 샘플을 용출시켰다(이동상 A: dH20중의 10 mM 암모늄 하이드록사이드, 이동상 B: 80% 아세토니트릴 및 20% 메탄올중의 10 mM 암모늄 하이드록사이드; 초기 3분간 20% B, 이후 4분내 95% B로 진입., 모든 유속은 0.4 mL/min). 9.1분에, 농도 구배는 초기 조건인 1분간 20 %B로 복귀시켰다. 서열번호 3은 1.45분에 분석용 컬럼에서 용출되었고, 삼단계 사중극자형 질량 분광계(triple-quadrapole mass spectrometry)(MRM, 764 (+2 charge state) > l82 (+1 charge state) Da; cone voltage = 30V; collision = 20 eV; parent resolution = 2 Da at base peak; daughter resolution = 2 Da at base peak)로 검출하였다. 기계적 반응을 화학 합성한 서열번호 3의 정량된 함량에 따른 표준 곡선과 비교하여 농도 단위로 변환하였고, 동일한 공정으로 마우스 혈청에 주사하였다.
도 10b는 LCMS에 의해 검출된 정맥내로 및 경구로 투여된 서열번호 3에 대한 흡수 데이터이다. 본 분석에서, 서열번호 3는 유사하게 최소한으로 전신 흡수되는 것으로 나타났으며, 생체이용성은 < 0.11 % 이다.
펩티드 및 GC -C 수용체 작용제의 투여
위장병의 치료에 있어서, 본 발명의 펩티드와 작용제를 경구로, 예컨대 정제, 미리 결정된 함량의 활성 성분을 포함하는 교갑(cachet), 젤, 펠렛, 페이스트, 시럽, 큰 환약(bolus), 연약(electuary), 슬러리, 사케트(sachet); 캡슐; 분말, 동결건조된 분말; 과립; 수계 액체 또는 비수계 액체중의 용액 또는 현탁액; W/O형 액체 에멀젼 또는 O/W형 액체 에멀젼; 리포좀 제형을 통해(예, EP 736299) 또는 다른 형태로 투여되는 것이 바람직하다. 정제와 같은 경구 투여 제형은 선택적으로 코팅되거나 표시될 수 있으며, 활성 성분의 지속적인, 지연된 또는 조절된 방출을 제공하기 위해 제형화될 수 있다. 상기 펩티드 및 작용제는 본원에 기재된 비제한적인 제제를 포함하는 취장병 치료에 사용되는 그외 제제와 병용 투여될 수 있다. 또한, 펩티드 및 작용제는 좌제(rectal suppository)로 투여될 수 있다. 울혈성 심부전증 및 양성 전립선 비대증과 같은 위장관 외부 질환의 치료를 위해, 펩티드 및 작용제는 비경구로 또는 경구로 투여되는 것이 바람직하다.
본 발명의 펩티드는 단독으로 또는 그외 제제와 조합하여 사용될 수 있다. 예컨대, 상기 펩티드는 전통성 펩티드 또는 화합물과 함께 투여될 수 있다. 상기 진통성 펩티드 또는 화합물은 본원의 펩티드에 공유결합에 의해 접착될 수 있으며, 또는 병용 요법으로 본원의 펩티드와 함께 투여되거나 연속적으로 투여되는 개별적인 제제일 수 있다.
병용 요법은 2이상의 제제, 예컨대 각각이 제형화되어 있으며 개별적으로 투여되는 본 발명의 펩티드 및 진통성 펩티드 또는 화합물을 투여함으로써 이룰수 있거나 또는 둘 이상의 제제를 하나의 제형으로 투여함으로써 이룰 수 있다. 그외 병용들 역시 병용 요법에 포함된다. 예를들면, 두가지 제제는 함께 제형화되고, 제 3의 제제를 함유하는 분리된 제형과 동시에 투여될 수 있다. 병용 요법에서 2 종 이상의 제제가 동시에 투여될 수 있으나, 필요치 않을 수 있다. 예컨대 제 1 제제(또는 제제의 조합)가 분, 시간, 일 또는 주의 간격으로 제 2 제제(또는 제제의 조합)에 선행 투여될 수 있다. 따라서, 2종 이상의 제제는 서로 수 분내 또는 서로간 1, 2, 3, 6, 9, 12, 15, 18 또는 24 시간내, 또는 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 일간, 또는 서로간 2, 3, 4, 5, 6, 7,, 8, 9 또는 10 주내에 투여될 수 있다.
일부 경우에서는, 간격이 보다 길 수 있다. 많은 경우들에서, 병용 용법에 사용되는 2종 이상의 제제는 동시에 환자의 체내에 존재되는 것이 바람직하지만, 그렇지 않을 수 있다.
병용 요법은 또한 병용으로 사용되는 제제 1종 이상을 2회 이상 투여하는 것을 포함할 수 있다. 예컨대, 제제 X와 제제 Y가 병용으로 사용되는 경우, 임의의 조합을 1회 이상으로 연속적으로 예컨대 X-Y-X, X-X-Y, Y-X-Y, Y-Y-X, X-X-Y-Y 등의 순서로 투여할 수 있다.
단독 또는 병용 형태의 제제는 모든 약리학적으로 허용가능한 담체 또는 매질과 조합될 수 있다. 따라서, 이들은 환자의 투여시 부작용, 알레르기 반응 또는 원치 않는 반응을 일으키지 않는 물질과 조합할 수 있다. 사용되는 담체 또는 매질은 용매, 분산제, 코팅제, 흡수 촉진제, 조절성 방출제 및 그외 무활성 부형제(전분, 폴리올, 과립화제, 미세결정형 셀룰로스, 희석제, 윤활제, 결합제, 붕괴제 등) 등을 포함할 수 있다. 필요에 따라, 상기 조성물의 정제 투여물을 표준적인 수계 또는 비수계 기법으로 코팅할 수 있다.
본 발명의 조성물은 또한 그외 치료학적 성분들, 고결 방지제(anti-caking agent), 보존제, 감미제, 착색제, 향료, 건조제, 가소제, 염료 등을 선택적으로 포함할 수 있다. 이러한 선택 성분들 모두 제형 안정성을 유지하기 위해 본 발명의 화합물과 혼화가능하여야 한다. 상기 조성물은 필요에 따라, 예컨대 락토스, 글루코스, 프럭토스, 갈락토스, 트레할로스, 슈크로스, 말토스, 라피노스, 말티톨, 멜레지토스, 스타키로스, 락티톨, 팔라티니트, 전분, 자일리톨, 만니톨, 미오이노시톨 등과, 이들의 수화물, 아미노산, 예컨대 알라닌, 글리신, 베타인, 펩티드 및 단백질, 예컨대 알부멘과 같은, 그외 첨가제를 포함할 수 있다.
약학적으로 허용가능한 담체 및 약학적으로 허용가능한 무활성의 담체 및 전술한 부가적인 성분으로서 사용가능한 부형제의 예로는, 하기에 기술한 것과 같은 결합제, 필러, 붕괴제, 윤활제, 항-미생물제, 및 코팅제가 있으나, 이로 한정되는 것은 아니다.
결합제: 옥수수 전분, 감자 전분, 그외 전분류, 젤라틴, 아카시아와 같은 천연 및 합성 검, 소듐 알기네이트, 알긴산, 그외 알기네이트류, 트라가칸트 분말, 구아르 검, 셀룰로스 및 그외 유도체들(예, 에틸 셀롤로스, 셀룰로스 아세테이트, 카르복시메틸 셀룰로스 칼슘, 소듐 카르복시메틸 셀룰로스), 폴리비닐 피롤리돈, 메틸 셀룰로스, 젤라틴 전처리된 전분(예, STARCH 1500® 및 STARCH 1500 LM®, Colorcon, Ltd.), 하이드록시프로필 메틸 셀룰로스, 미세결정형 셀룰로스(예, AVICELTM, 예컨대, AVICEL-PH-1O1TM, -1O3TM 및 -1O5TM, FMC Corporatiomi, Marcus Hook, PA, USA), 또는 이들의 혼합물,
필러: 탈크, 칼슘 카르보네이트(예, 과립 또는 분말), 디베이직 칼슘 포스페이트(dibasic calcium phosphate), 트리베이직 칼슘 포스페이트, 칼슘 설페이트(예, 과립 또는 분말), 미세결정형 셀룰로스, 셀룰로스 분말, 덱스트레이트(dextrate), 카올린, 만니톨, 실리식산, 소르비톨, 전분, 젤라틴 전처리한 전분 또는 이들의 혼합물,
붕괴제: 아가-아가, 알긴산, 칼슘 카르보네이트, 미세결정형 셀룰로스, 크로스카르멜로스 소듐(croscarmeilose sodium), 크로스포비돈(crospovidone), 폴아크릴린 포타슘(polacrilin potassium), 소듐 스타치 글리콜레이트, 감자 또는 타피오카 전분, 그외 전분류, 젤라틴 전처리된 전분, 클레이, 그외 알긴류, 그외 셀룰로스, 검 또는 이들의 혼합물,
윤활제: 칼슘 스테아레이트, 마그네슘 스테아레이트, 미네랄 오일, 라이트 미네랄 오일, 글리세린, 소르비톨, 만니톨, 폴리에틸렌 글리콜, 그외 글리콜류, 스테아르산, 소듐 라우릴 설페이트, 탈크, 수소화된 식물성 오일(예, 피넛 오일, 면실유, 해바라기유, 참깨 오일, 올리브유, 옥수수유 및 콩 오일), 아연 스테아레이트, 에틸 올레이트, 에틸 라우레이트, 아가, 실로이드 실리카겔(AEROSIL 200, W.R. Grace Co., Baltimore, MD USA), 합성 실리카의 공동 응집된 에어로줄(coagulated aerosol)(Deaussa Co., Piano, TX USA), 피로제닉 실리콘 디옥사이드(CAB-O-SIL, Cabot Co., Boston, MA USA) 또는 이들의 혼합물,
고결 방지제: 칼슘 실리케이트, 마그네슘 실리케이트, 실리콘 디옥사이드, 콜로이달 실리콘 디옥사이드, 탈크 또는 이들의 혼합물
항-미생물제: 벤즈알코늄 클로라이드, 벤즈에토늄 클로라이드, 벤조산, 벤질 알콜, 부틸 파라빈, 세틸피리디늄 클로라이드, 크레졸, 클로로부탄올, 디하이드로아세트산, 에틸파라빈, 메틴파라빈, 페놀, 페닐에틸 알콜, 페녹시에탄올, 페닐머큐리 아세테이트, 페닐머큐리 니트레이트, 포타슘 소르베이트, 프로필파라빈, 소듐 벤조에이트, 소듐 디하이드로아세테이트, 소듐 프로피오네이트, 소르브산, 티메르졸(thimersol), 티모 또는 이들의 혼합물, 및
코팅제: 소듐 카르복시메틸 셀룰로스, 셀룰로스 아세테이트 프탈레이트, 에틸셀룰로스, 젤라틴, 약용 글레이즈, 하이드록시프로필 셀룰로스, 하이드록시프로필 메틸셀룰로스, 하이드록시프로필 메틸 셀룰로스 프탈레이트, 메틸셀룰로스, 폴리에틸렌 글리콜, 폴리비닐 아세테이트 프탈레이트, 셀락, 슈크로스, 티타늄 디옥 사이드, 카르나우바 왁스, 미세결정형 왁스 또는 이들의 혼합물.
유리 형태이거나 또는 염 형태의 제제는, 폴리아세틱-글리콜록익 산(PLGA), 폴리-(I)-락틱-글리콜릭-타르타릭산(P(I)LGT)(WO 01/12233), 폴리글리콜산(미국 특허 3,773,919), 폴리락트산(미국 특허 4,767,628), 폴리(ε-카프롤락톤) 및 폴리(알킬렌 옥사이드)(미국 특허 20030068384)과 같은 폴리머와 조합하여, 서방성 제형(sustained release formulation)을 제조할 수 있다. 이러한 제형은 또한 폴리머, 폴리머의 입자 크기 및 임플란트의 크기에 따라 수일, 수주 또는 수 개월동안 펩티드나 그외 제제를 방출하는 임플란트에 사용할 수 있다(예, 미국 특허 6,620,422). 사용가능한 그외 서방형 제형 및 폴리머는 EP 0 467 389 A2, WO 93/24150, 미국 특허 5,612,052, WO 97/40085, WO 03/075887, WO 01/0l964A2, 미국 특허 5,922,356, WO 94/155587, WO 02/074247A2, WO 98/25642, 미국 특허 5,968,895, 미국 특허 6,180,608, 미국 특허 20030171296, 미국 특허 20020176841, 미국 특허 5,672,659, 미국 특허 5,893,985, 미국 특허 5,134,122, 미국 특허 5,192,741, 미국 특허 5,192,741, 미국 특허 4,668,506, 미국 특허 4,713,244, 미국 특허 5,445,832 미국 특허 4,931,279, 미국 특허 5,980,945, WO 02/058672, WO 9726015, WO 97/04744, 및 US 20020019446에 개시되어 있다. 이러한 서방성 제형에서, 펩티드의 미세입자는 폴리머의 미세입자와 조합된다. 1종 이상의 서방형 임플란트는 대장, 소장 또는 둘다에 위치될 수 있다. 미국 특허 6,011,011 및 WO 94/06452는 폴리에틸렌 글리콜(PEG 300 및 PEG 400) 또는 트리아세틴 중 어느 하나를 사용한 서방성 제형을 개시하고 있다. WO 03/053401은 생체이용성을 증가시키 고, 위장관에서 제제의 조절성 방출을 제공할 수 있는 제형을 개시하고 있다. 다른 조절성 방출 제형은 WO 02/38129, EP 326 151, 미국 특허 5,236,704, WO 02/30398, WO 98/13029; 미국 특허 20030064105, 미국 특허 20030138488A1, 미국 특허 20030216307A1, 미국 특허 6,667,060, WO 01/49249, WO 01/49311, WO 01/49249, WO 01/49311 및 미국 특허 5,877,224에 개시되어 있다.
제제는 예컨대 정맥 주사, 근육내 주사, 피하 주사, 복막내 주사, 국소, 설하, 동맥내(관절내), 진피내, 구강(buccal), 눈(안내 포함), 코내(캐뉼라 사용 포함), 척수내, 척수강내 또는 그외 경로로 투여될 수 있다. 제제는 경구로, 예컨대 정제, 미리 결정된 함량의 활성 성분을 포함하는 교갑(cachet), 젤, 펠렛, 페이스트, 시럽, 큰 환약(bolus), 연약(electuary), 슬러리, 캡슐, 분말, 동결건조한 분말, 과립, 사케트(sachet), 수계 액체 또는 비수계 액체중의 용액 또는 현탁제로서, W/O형 액체 에멀젼 또는 O/W형 액체 에멀젼, 마이셀 제형으로(WO 97/11682), 리포좀 제형으로(예, EP 736299,WO 99/59550 및 WO 97/13500), WO 03/094886에 기재된 제형을 통해, 또는 그외 일부 형태로, 투여될 수 있다. 경구 투여 조성물은 결합제, 윤활제(lubricant), 무활성 희석제, 윤활제, 표면활성제, 분산제, 향료제, 및 습윤제를 포함할 수 있다. 정제와 같은 경구 투여 제형은 선택적으로 코팅되거나 또는 자국이 표시될 수 있으며, 활성 성분의 서방성, 지연성 또는 조절성을 제공하기 위해 제형화될 수 있다. 제제는 또한 경피(즉, 저장체 타입 또는 매트릭스 타입의 패치, 미세바늘, 열성 천공(thermal poration), 피하용 바늘(hypodermic needle), 이온도입법(iontophoresis), 전기충격(electroporation), 초음파 또는 그 외 소노포레시스(sonophoresis), 젯 주사(jet injection), 또는 선행 방법들을 병용하여 투여할 수 있다(Prausnitz et al. 2004, Nature Reviews Drug Discovery 3:115-124). 제제는 미국 특허 20020061336에 개시된 하이드로겔 입자 제형을 이용하여 고속 경피 입자 주입으로 투여할 수 있다. 추가적인 입자 제형은 WO 00/45792, WO 00/53160 및 WO 02/19989에 기재되어 있다. 고약(plaster) 및 흡수 촉진제 디메틸이소소르비드(absorption promoter dimethylisosorbide)를 포함하는 경피 제형의 예를 WO 89/04179에서 볼수 있다. WO 96/11705는 경피 투여에 적합한 제형을 제시하고 있다. 제제는 좌제의 형태로 투여되거나 또는 그외 질 또는 직장을 통한 방법으로 투여될 수 있다. 제제는 WO 90/07923에 개시된 경막 제형으로 투여될 수 있다. 제제는 미국 특허 6,485,706에 개시된 탈수 입자를 통해 비-침투적으로 투여될 수 있다. 제제는 WO 02/49621에 개시된 장-코팅된 약물 제형 형태로 투여될 수 있다. 제제는 미국 특허 5,179,079에 개시된 제형을 이용하여 비강내로 투여될 수 있다. 비경구 주입에 적합한 제형들은 WO 00/62759에 개시되어 있다. 제제는 미국 특허 20030206939 및 WO 00/06108에 개시된 카세인 제형을 이용하여 투여될 수 있다. 제제는 미국 특허 20020034536에 개시된 미립자 제형을 이용하여 투여될 수 있다..
단독 또는 그외 적합한 성분과 병용 형태의 제제는 기관내 주입(intratracheal instillation)(주사기로 용액으로 폐로 전달), 리포좀의 기관내 전달, 취분법(insufflation)(주사기나 그외 유사한 임의 장비로 분말 제형을 폐로 투여) 및 에어로졸 흡입을 비제한적으로 포함하는 여러가지 기법을 활용한 폐 경로 로 투여될 수 있다. 또한, 에어로졸(예, 젯 또는 초음파 연무기(nebulizer), 정량식 흡입기(metered-dose inhaler)(MDIs), 및 건조 분말 흡입기(DPIs))을 비강내 적용에 사용할 수 있다. 에어로졸 제형은 가스상 매질중의 고형 물질 및 액상 방울의 안정적인 분산제 또는 현탁제이며, 하이드로플루오로알칸(HFA, 즉 HFA-l34a 및 HFA-227, 또는 이들의 혼합물), 디클로로디플루오로메탄(또는 프로펠런트 11, 12 및/또는 114의 혼합물과 같은 그외 클로로플루오카르본 프로펠런트), 프로판, 나이트로겐 등과 같은, 허용가능한 가압성 추진제(pressurized acceptable propellant)에 둘 수 있다. 폐 제형은 지방상, 사카라이드, 킬레이트제, 효소 저해제(예, 프로테아제 저해제), 보강제(예, 글리코콜레이트, 서펙틴(surfactin), 스판85 및 나파모스타트(nafamostat)), 보존제(예, 벤즈알코늄 클로라이드 또는 클로로부탄올), 및 에탄올(정상적으로는 최대 5%이며, 가능한 최대 20 중량%)와 같은 투과 증강제를 포함할 수 있다. 에탄올은 계량 밸브의 기능을 향상시키며, 또한 일부 경우들에서는 분산 안정성을 향상시킬 수 있어, 일반적으로 에어로 제형에 함유된다. 폐 제형 또한 담즙산 및 미국 특허 6,524,557과 본원의 참조문헌에 개시된 것을 비제한적으로 포함하는 계면활성제를 함유할 수도 있다. 미국 특허 6,524,557에 개시된 계면활성제, 예컨대 C8-C16 지방산 염, 담즙산염, 인지질 또는 알킬 사카라이드는 이들의 일부가 제형내 펩티드의 흡수를 증강시킨다는 보고가 있은 바, 이롭다. 또한, 치료학적인 유효량의 활성 화합물과 이와 혼합된 적정 담체를 포함하며, 건조 분말 흡입기로 사용하게 고안된 건조 분말 제형이 본 발명에 적합하다. 본 발명의 건조 분말 제형에 첨가될 수 있는 흡수 증강제가 미국 특허 6,632,456에 개시 되어 있다. WO 02/080884는 분말의 표면을 변형시키는 새로운 방법을 제시하고 있다. 에어로졸 제형으로는, 미국 특허 5,230,884, 미국 특허 5,292,499, WO 01/78694, WO 01/78696, 미국 특허 2003019437, 미국 특허 20030165436, 및 WO 96/40089 (식물성 오일 포함)이 있다. 흡입에 적합한 서방성 제형은 미국 특허 20010036481A1, 20030232019A1, 20040018243A1, WO 01/13891, WO 02/067902, WO 03/072080 및 WO 03/079885에 개시되어 있다. 미세입자를 포함하는 폐 제형은 WO 03/015750, 미국 특허 20030008013 및 WO 00/00176에 개시되어 있다. 안정한 유리상의 분말을 포함하는 폐 제형은 미국 특허 20020141945 및 미국 특허 6,309,671에 개시되어 있다. 그외 에어로졸 제형은 EP 1338272A1, WO 90/09781, 미국 특허 5,348,730, 미국 특허 6,436,367, WO 91/04011 및 미국 특허 6,294,153에 개시되어 있으며, 미국 특허 6,290,987은 에어로졸 또는 그외 수단으로 투여될 수 있는 리포좀계 제형을 개시하고 있다. 흡입용 분말 제형은 미국 특허 20030053960 및 WO 01/60341에 개시되어 있다. 제제는 미국 특허 20010038824에 개시된 바와 같이 비강내로 투여할 수 있다.
완충화된 염수 및 유사 비히클중의 약제 용액은 연무기내에서 에어로졸을 형성하는데 일반적으로 채택된다. 유사한 연무기는 베르누이 원리에 따라 작동하고, 스프레이 입자를 만들기 위해 공기나 산소 기류를 사용한다. 보다 복잡한 연무기는 초음파를 사용하여 스프레이 입자를 만든다. 이들 타입들은 당업계에 널리 공지되어 있으며, Sprowls' American Pharmacy and Remington's The Science and Practice of Pharmacy와 같은 약학의 표준 교재에 기재되어 있다. 그외 에어로졸 형성용 장치들은 응축 가스, 일반적으로 하이드로플루오로카르본 및 클로로플루오로카르본을 사용하며, 이들은 가압 용기내에서 약제와 임의의 필수 부형제와 혼합되며, 상기 장치는 Sprowls 및 Remington과 같은 표준 교재에 개시된 것과 유사하다.
제제는 유리 산 또는 염일, 또는 그것의 약리학적으로 허용가능한 염일 수 있다. 고형물은 투여 바로 전이나, 이전에 용해 또는 분산시킬 수 있다. 일부 경우, 조제물은 미생물의 생육을 방지하기 위해 보존제를 함유한다. 주사용으로 적합한 약학적 형태는, 예컨대 물, 알코올, 유기 용매, 오일 또는 그외 용매 또는 분산제(예, 글리세롤, 프로필렌 글리콜, 폴리에틸렌 글리콜 및 식물성 오일)을 포함하는, 멸균한 수계 또는 유기성 용액이나 분산액을 함유할 수 있다. 상기 제형은 항산화제, 완충제, 세균사멸제, 제형을 목적한 대상체의 혈액과 등장성이 되게하는 용질, 현탁제, 가용화제, 증점제, 안정화제 및 보존제를 포함할 수 있는 수계 및 비수계 멸균 현탁제를 포함할 수 있다. 약학적 제제는 여과 멸균화 또는 그외 적합한 방법으로 멸균시킬 수 있다. 제제는 면역글루불린 또는 알부민과 융합될 수 있으며, 또는 리포좀내로 병합되어 반감기를 개선시킬 수 있다. 또한, 제제는 폴리에틸렌 글리콜(PEG) 체인에 접합될 수 있다. 페길화 방법 및 PEG-접합체(즉, PEG계 하이드로겔, PEG 변형 리포좀)을 포함하는 추가적인 제형은 Harris and Chess, Nature Reviews Drug Discovery 2: 214-221 및 첨부된 참조문헌들에서 확인할 수 있다. 또한, 펩티드는 알킬 기(예, 탄소수 1 내지 20의 선형 또는 분지형의 알킬기), 지방산 라디컬 및 PEG, 알킬기와 지방산 라디칼의 조합을 이용하여 변형 될 수 있다(미국 특허 Patent 6,309,633; Soltero et al., 2001 Innovations in Pharmaceutical Technology 106-110). 제제는 나노코클레이트(nanocochieate) 또는 코클레이트 전달 비히클(BioDelivery Sciences International)을 통해 투여될 수 있다. 제제는 미국 특허 5,204,108에 개시된 바와 같은 제형을 이용하여 경점막으로(즉, 질, 눈 또는 코와 같은 점막 표면을 투과하여) 전달될 수 있다. 제제는 WO 88/01165에 개시된 바와 같이 미세캡슐 형태로 제조될 수 있다. 제제는 미국 특허 20020055496, WO 00/47203 및 미국 특허 6,495,120에 개시된 제형을 이용하여 입안으로 투여될 수 있다. 제제는 WO O1/91728A2에 개시된 나노에멀젼 제형을 이용하여 전달될 수 있다.
본 발명에 있어서 적합한 약학적 조성물은 일반적으로 상당량의 활성 화합물과, 약학적으로 허용가능한 희석제 또는 부형제, 예컨대 멸균 수용액을 사용 목적에 따라 최종 농도로 포함할 것이다. 제조 기법은 Remington's Pharmaceutical Sciences (18th Edition, Mack Publishing Company, 1995)에 예시된 바와 같이, 당업계에 널리 공지되어 있다.
본원에 기재된 제제 및 병용 치료제는, 각각 포장되거나 또는 개별 제형화된 2종 이상의 제제를 일회분으로 또는 여러회분으로 포함하거나, 또는 2종 이상의 제제가 조합하여 포장되거나 제형화된 것을 일회분으로 또는 여러회분으로 포함하는 키트로서 포장될 수 있다. 따라서, 하나 이상의 제제를 제1 용기내에 존재시킬 수 있으며, 키트는 선택적으로 제2 용기에 하나 이상의 제제를 함유할 수 있다. 용기 또는 용기들은 패키지내에 포함되며, 패키지는 선택적으로 투여 또는 복용 지침서 를 동봉할 수 있다. 키트는 주사기 또는 제제뿐만 아니라 희석제를 투여하기 위한 그외 수단이나, 또는 그외 제형을 위한 수단과 같은 추가적인 구성을 포함할 수 있다.
본원의 제제의 화학적 및/또는 물리적 안정성을 증가시키기 위한 방법은 미국 특허 6,541,606, 미국 특허 6,068,850, 미국 특허 6,124,261, 미국 특허 5,904,935, WO 00/15224, 미국 특허 20030069182(니코틴아미드의 첨가를 통해), 미국 특허 2003O17523OA1, 미국 특허 2003Ol75230Al, 미국 특허 2003O175239A1, 미국 특허 20020045582, 미국 특허 20010031726, WO 02/26248, WO 03/014304, WO 98/00152A1, WO 98/0O157Al, WO 90/12029, WO 00/04880, WO 91/04743, WO 97/04796 및 첨부된 참조문헌에서 확인된다.
본원의 제제의 생체이용성을 증가시키기 위한 방법은 미국 특허 6,008,187, 미국 특허 5,424,289, 미국 특허 20030198619, WO 90/01329, WO 01/49268, WO 00/32172, 및 WO 02/064166에서 확인된다. 또한, 흡수 증강제로서 글리시리지네이트(Glycyrrhizinate)를 사용할 수 있다(예, EP397447). WO 03/004062는 본 발명의 제제를 위장관으로 표적화하기 위해 사용될 수 있는 Ulex 유로파우스(europaeus I)(UEA1)과 UEAI 모방체를 다루고 있다.
본 발명의 제제는 혈청 단백질 트랜스페린(transferrin)의 변형된 형태에 융합시킬 수 있다. 트랜스페린 융합 단백질의 제조 및 용도는 미국 특허 20030221201, 미국 특허 20040023334, 미국 특허 20030226155, WO 04/020454, 및 WO 04/019872에서 논의되고 있다. 트랜스페린 융합 단백질은 순환성 반감기와 효 능을 증가시키고, 부적절한 부작용을 감소시키고, 투여량을 낮출 수 있다.
본 발명의 펩티드 및 작용제는 세균에서 재조합 발현시킬 수 있다. 펩티드 또는 작용제를 발현하는 세균을 경구로, 직장으로, 점막으로 또는 본원에 기재된 방법을 비제한적으로 포함하는 일부 다른 투여 방식을 통해 투여할 수 있다.
병용요법에서의 진통제
본 발명의 펩티드 또는 작용제는 진통제, 예 진통성 화합물 또는 진통성 펩티드와 병용 요법으로 사용될 수 있다. 이들 펩티드 및 화합물은 본 발명의 펩티드와 (동시에 또는 순차적으로) 투여할 수 있다. 또한, 이는 치료적 접합체를 만들기 위해 본원에 기재된 제제에 공유결합으로 연결되거나 또는 부착될 수 있다. 사용가능한 진통제들로는 Ca 채널 차단제, 5HT 수용체 길항제(예, 5HT3, 5HT4 및 5HT1 수용체 길항제), 오피오이드 수용체 작용제 (로페라미드, 페도토진 및 펜타닐), NK1 수용체 길항제, CCK 수용체 작용제(예, 록시글루미드), NK1 수용체 길항제, NK3 수용체 길항제, 노르에피네프린-세로토닌 재흡수 저해제(NSRI), 바닐로이드(vanilloid) 및 캐나바노이드(cannabanoid) 수용체 작용제, 및 시알로르핀(sialorphin)이 있다. 다양한 분류의 진통제가 문헌에 개시되어 있다.
사용가능한 진통성 펩티드들로는 아미노산 서열 QHNPR(SEQ ID NO:), VQHNPR(서열번호), VRQHNPR(서열번호), VRGQHNPR(SEQ ID NO :), VRGPQHNPR(SEQ ID NO :), VRGPRQHNPR(서열번호), VRGPRRQHNPR(서열번호) 및 RQHNPR(서열번호)를 포함하는 펩티드를 포함한, 시알로르핀-관련 펩티드가 있다. 시알로르핀-관련 펩티드는 네프릴리신(neprilysin)에 결합하여 물질 P 및 Met-엔케팔린의 네프릴리신 매개 성 분해(neprilysin-mediated breakdown of substance P and Met-enkephalin)를 저해한다. 따라서, 네프릴리신의 저해제인 화합물 또는 펩티드는 병용 용법으로 본 발명의 펩티드와 함께 투여할 수 있거나 또는 본 발명의 펩티드와 예컨대 공유 결합에 의해 링크될 수 있는 진통제로 유용하다. 시알로르핀 관련 펩티드는 미국 특허 6,589,750, 미국 특허 공개공보 20030078200 Al 및 WO 02/051435 A2에 개시되어 있다.
오피오이드 수용체 길항제와 작용제는 본 발명의 펩티드와 병용 요법으로 함께 투여되거나 또는 본 발명의 펩티드와 예컨대 공유결합을 통하여 연결될 수 있다. 예를들면, 날록손(naloxone), 날트렉손(naltrexone), 메틸 날로존(methyl nalozone), 날메펜(nalmefene), 키프리딤(cypridime), 베타 퍼날트렉사민(beta funaltrexamine), 날록소나진(naloxonazine), 날트린돌(naltrindole) 및 노르-비날토르피민(nor-binaltorphimine)과 같은 오피오이드 수용체 길항제는 IBS 치료에 유용한 것으로 여겨진다. 상기한 유형의 오피오이드 길항제는 지연성 방출 제형 및 서방성 제형으로 제형화하는데 사용할 수 있어, 길항제의 개시 방출을 중간에서 소장 말단 및/또는 하위 결장까지 이루어지게 할 수 있다. 이러한 길항제들은 WO 01/32180A2에 개시되어 있다. 엔케팔린 펜타펩티드(HOE825; Tyr-D-Lys-Gly-Phe-L-호모세린)은 μ 및 δ 오피오이드 수용체들의 작용제이며, 장 운동을 증가시키는데 유용한 것으로 간주되고 있으며(Eur. J. Pharm. 219: 445, 1992), 상기 펩티드는 본 발명의 펩티드와 함께 사용될 수 있다. 또한 μ/δ/κ 오피오이드 수용체에 결합하여 모틸린의 분비를 활성화하고 가스트린, 바소엑티브 장 펩티드, 가스트린 및 글루카곤의 분비를 매개하는 것으로 여겨지는 트리메부틴(trimebutine)이 유용한다. 페도토진(fedotozine), 아시마돌린(asimadoline) 및 케토사이클라조신(ketocyclazocine)과 같은 κ 오피오이드 수용체 작용제와 WO 03/097051 A2에 개시된 화합물은 본 발명의 펩티드와 함께 사용하거나 또는 연결시킬 수 있다. 또한, 모르핀, 디페닐옥실레이트, 프레이크파미드(frakefamide)(H-Tyr-D-Ala-Phe (F)-Phe-NH2; WO 01/019849 Al) 및 로페라미드(loperamide)와 같은 μ 오피오이드 수용체를 사용할 수 있다.
Tyr-Arg(키오토르핀(kyotorphin))은 메트-엔케팔린의 분비를 자극하여 진통성 효과를 발생시키는 디펩티드이다(J. Biol. Chem 262:8165, 1987). 키오토르핀은 본 발명의 펩티드와 함께 사용하거나 또는 연결시킬 수 있다.
크로모그라닌(chrommogranin) 유래 펩티드(CgA 47-66, 예, Ghia et al. 2004 Regulatory Peptides 119: 199)는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
양서류 또는 그외 종에서 유래된 캐룰레인(caerulein)와 같은 CCK 수용체 작용제는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있는 유용한 진통제이다.
코노톡신(Conotoxin) 펩티드는 전압 개폐성 칼슘 채널, NMDA 수용체 또는 니코틴 수용체에 작용하는 거대 진통성 펩티드 클래스 중 하나이다. 상기 펩티드는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
티물린(thymulin)의 펩티드 유사체(FR Application 2830451)는 진통 활성을 가질 수 있으며, 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
록시글루미드(loxiglumide) 및 덱슬록시글루이드(dexloxiglumide)(록시글루미드의 R-이성체)(WO 88/05774)을 포함한 CCK(CCKa 또는 CCKb) 수용체 길항제는 진통 활성을 가질 수 있으며, 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
그외 유용한 진통제로, 테가세로드(tegaserod)/젤노름(zelnorm®), 모사프리드(mosapride), 메토클로프라미드(metociopramide), 자코프리드(zacopride), 시사프리드(cisapride), 렌자프리드(renzapride), 벤즈이미다졸론 유도체, 예컨대 BIMU 1 및 BIMU 8, 및 리렉사프리드(lirexapride)와 같은 5-HT4 작용제를 포함한다. 상기 작용제는 EP1321142 A1, WO 03/053432A1, EP 505322 Al, EP 505322BI, 미국 특허 5,510,353, EP 507672Al, EP 507672 B1, 및 5,273,983에 개시되어 있다.
지코노티드(ziconotide)와 예컨대 EP625162B1, 미국 특허 5,364,842, 미국 특허 5,587,454, 미국 특허 5,824,645, 미국 특허 5,859,186, 미국 특허 5,994,305, 미국 특허 6,087,091, 미국 특허 6,136,786, WO 93/13128Al, EP 1336409Al, EP 835126Al, EP 835126 B1, 미국 특허 5,795,864, 미국 특허 5,891,849, 미국 특허 6,054,429, WO 97/01351 Al에 개시된 관련 화합물과 같은 칼슘 채널 차단제는, 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
NK-1, NK-2, 및 NK-3 수용체의 다양한 길항제(Giardina et al. 2003 Drugs 6:758)는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
아프레피탄트(aprepitant)(Merck & Co Inc), 보포피탄트(vofopitant), 에즐로피탄트(ezlopitant)(Pfizer, Inc.), R-673(Hoffmann-La Roche Ltd), SR-48969(Sanofi Synthelabo), CP-122,721(Pfizer, Inc.), GW679769(Glaxo Smith Kline), TAK-637(Takeda/Abbot), SR-14033 및 예컨대 EP 873753Al, US 20010006972Al, US 20030109417Al, WO 01/52844 Al에 개시되어 있는 관련 화합물과 같은 NK1 수용체 길항제는, 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
네파두탄트(nepadutant)(Menarini Ricerche SpA), 사레두탄트(saredutant)(Sanofi-Synthelabo), GW597599(Glaxo Smith Kline), SR-144190(Sanofi-Synthelabo) 및 UK-290795(Pfizer Inc.)와 같은 NK-2 수용체 길항제는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
오사네탄트(osanetant)(SR-142801; Sanofi-Synthelabo), SSR-241586, 탈네탄트(talnetant) 및 WO 02/094187 A2, EP 876347Al, WO 97/21680Al, 미국 특허 6,277,862, WO 98/11090, WO 95/28418, WO 97/19927, 및 Boden 등(J Med Chem. 39: 1664-75, 1996)에 개시된 관련 화합물과 같은, NK3 수용체 길항제는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
밀나시프란(milnacipran) 및 WO 03/077897 Al에 개시된 관련 화합물과 같은 노르에피네프린-세로토닌 재흡수 저해제는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
아르바닐(arvanil) 및 WO 01/64212 Al에 개시된 관련 화합물과 같은 바닐로 이드(Vanilloid) 수용체 길항제는 본 발명의 펩티드와 함께 사용하거나 연결시킬 수 있다.
진통성 펩티드 및 화합물은 본 발명의 펩티드 및 작용제와 (동시에 또는 순차적으로) 투여할 수 있다. 또한 진통제는 치료학적 접합체를 제조하기 위해 본 발명의 펩티드 및 작용제와 공유 결합으로 연결시킬 수 있다. 진통제가 펩티드이고, 본 발명의 제제와 공유결합으로 연결된 경우, 제조되는 펩티드는 또한 하나 이상의 트립신 절단 부위를 포함할 수도 있다. 펩티드내에 존재하는 경우, 상기 진통성 펩티드는 진통성 펩티드의 분리를 허용하는 트립신 절단 부위의 하위(카르복시 말단에 있는 경우)에 있거나 또는 상위(아미노 말단에 있는 경우)에 있을 수도 있다.
시알로르핀-관련 펩티드 뿐만 아니라, 진통성 펩티드로 AspPhe, 엔도모르핀-1, 엔도모르핀-2, 노시스타틴, 달라긴, 루프론, 지크노티드 및 물질 P가 있다.
병용요법용 그외 제제들
또한, 본 발명은 본 발명의 펩티드 또는 작용제와 제2의 치료제를 포함하는 약학적 조성물을 포함한다. 제2의 치료제는 제2의 치료제를 이용한 치료에 대한 일차 징후(primary indication)로 간주되지 않는 증상을 포함한, 이용가능한 임의의 증상을 치료하기 위해 투여될 수 있다. 상기 제2의 치료제는 동시에 또는 순차적으로 투여될 수 있다. 제2의 치료제는 본 발명의 펩티드 및 작용제와 공우결합으로 연결되어, 치료학적 접합체를 만들 수 있다. 제2의 치료제가 또다른 펩티드인 경우, 본원에 기재된 것을 포함한 링커를 본 발명의 펩티드와 제2의 치료제 펩 티드 사이에 사용할 수 있다.
위장 및 그외 질환을 치료하기 위한 추가적인 치료제의 예는 다음과 같다:
(1) 변비 치료제(예, 이환성 지방산, 루비프로스톤(Lubiprostone)(SPI-0211; Sucampo Pharmaceuticals, Inc.; Bethesda, MD)과 같은 클로라이드 채널 활성자, 미라렉스(MiraLax)와 같은 하제(laxative); Braintree Laboratories, Braintree MA);
(2) 프로톤 펌프 저해제(예, 오메프라졸(Prilosec®), 에소메프라졸(Nexium®), 란소프라졸(lansoprazole)(Prevacid®), 판토프라졸(pantoprazole)(Protonix®) 및 라베프라졸(rabeprazole)(Aciphex®))과 같은 산 환원제 및 히스타민 H2-수용체 길항제(또한 시메티딘(cimetidine), 라니티딘(ranitidine), 파모티딘(famotidine) 및 니자티딘(nizatidine)을 포함한 H2-수용체로서 알려져 있음);
(3) 메토클로프라미드(metociopramide)(Reglan®), 돔페리돈(domperidone)(Motilium®), 에리트로마이신(erythromycin) 또는 시사프리드(cisapride)(propuisid®)를 포함한 운동촉진제(prokinetic agent);
(4) 바소스타틴 유래 펩티드, 크로모그라닌 A(4-6) (Ghia et al. 2004 Regulatory Peptides 121:3 1) 또는 모틸린 작용제(예, GM-611 또는 미템시날 퓨마레이트(mitemcinai fumarate))와 같은 소화관 운동 촉진제(pro-motility agent);
(5) 완전 또는 일부 5HT(예, 5HT1, 5HT2, 5HT3, 5HT4) 수용체 작용제 또는 길항제(5HT4 수용체 작용제(예, 테가세로드(ZELNORM®), 모사프리드, 메토클로프라미드, 자코프리드, 시사프리드, 렌자프리드, 벤즈이미다졸론 유도체, 예컨대 BIMU 1 및 BIMU 8, 및 리렉사프리드, 이들 작용제는 EP1321142 Al, WO 03/O53432A1, EP 505322 Al, EP 505322 Bl, 미국 특허 5,510,353, EP 507672 Al, EP 507672 Bl, 및 미국 특허 5,273,983에 개시되어 있음); 5HT3 수용체 작용제, 예컨대 MKC-733; 및 5HT3 수용체 작용제, 예컨대 알로세트론(alosetron) 및 ATI-7000 (Aryx Therapeutics, Santa Clara CA);
(6) 무스카린 수용체 작용제;
(7) 항-염증제;
(8) 진경제(antispasmodic);
(9) 항우울제;
(10) 오피오이드 수용체 작용제, 오피오이드 수용체 길항제(예, 날트렉손)과 같은 중추적으로 작용하는 진통제;
(11) 염증성 장 질환 치료제;
(12) 크론씨 병 및/또는 궤양성 직장염(예, alequel(Enzo Biochem, Inc.; Farmingsale, NY) 치료제, 항염증성 펩티드 RDP58(Genzyme, Inc.; Cambridge, MA), 및 TRAFICET-ENTM (ChemoCentryx, Inc.; San Cabs, CA);
(13) 위장 또는 내장 통증 치료제;
(14) 본 명세서에 기재된 것을 비제한적으로 포함하는 PDE(phosphodiesterase) 저해제;
(15) 장으로 유체를 끌어내는 하제(purgative)(예, VISICOL®, 소듐 포스페이트 모노베이직 모노하이드레이트와 소듐 포스페이트 디베이직 안하이드레이트의 조합);
(16) 코르티코트로핀 방출 인자(Corticotropin Releasing Factor, CRF) 수용체 길항제(NBI-34O41(Nenrocrine Biosciences, San Diego, CA), CRH9-4l, 아스트레신(astressin), R1219l9 (Janssen Pharmaceutica), CP154,526, NBT-27914, 암탈라르민(Antalarmin), DMP696 (Bristol-Myers Squibb) CP-316,311(Pfizer, Inc.), GW876008 (Neurocrine/Giaxo Smith Kline), ONO-2333Ms(Ono Pharmaceuticals), TS-041(Janssen), AAG561(Novartis) 및 미국 특허 5,063,245, 미국 특허 5,861,398, 미국 특허 20040224964, 미국 특허 20040198726, 미국 특허 2004O176400, 미국 특허 2004017l607, 미국 특허 20040110815, 및 미국 특허 20040006066에 기재된 것을 포함함);
(17) 글루카곤계 펩티드(glp-1)과 그것의 유사체(엑센딘-4(exendin-4) 포함), 및 DPP-IV(DPP-lV는 glp-1의 불활성화를 매개함) 저해제;
(18) 토피소팜(tofisopam), 거울상이성질적으로 순수한 R-토피소팜(enantiomerically-pure R-tofisopam) 및 그것의 약학적으로 허용가능한 염(US 20040229867);
(19) 디벤조티아제핀 유형의 3환성 항우울제, 티아넵틴(tianeptine)(Stablon®) 및 미국 특허 6,683,072에 개시된 그외 제제;
(20) (E)-4(1,3비스(사이클로헥실메틸)-1,2,3,4-테트라하이드로-2,6-디오노-9H-퓨린-8-일)신남산 노나에틸렌 글리콜 메틸 에테르 에스테르 및 WO 02/067942에 개시된 관련 화합물; 및
(20) 위장병 치료에 유용한 미생물을 함유하고 있는 생균성 PROBACTRIX®(The BioBalance Corporation; New York, NY).
본 발명의 펩티드 및 작용제는 대립유전자 변이체를 포함하는 생물학적으로 활성인 변이체를 포함한 영장류, 설취류 또는 토끼의 인슐린을 포함하는 인슐린, 보다 바람직하기로는 재조합 형태의 인간 인슐린 및 관련 화합물과 함께 병용요법으로 사용할 수 있다. 인간 인슐린의 소스(source)는 Eli Lilly(Indianapolis, Ind. 46285)에서 Humulin.TM. (human insulin rDNA origin)로 구입할 수 있는 바와 같은 약학적으로 허용가능하며 멸균된 제형을 포함한다. THE PHYSICIAN'S DESK REFERENCE, 55th Ed. (2001) Medical Economics, Thomson Healthcare(그외 적합한 인간 인슐린 개시)를 참조한다. 또한, 본 발명의 펩티드는 인슐린 효과나 투여 대상의 수준을 부양시킬 수 있는 제제, 예로, 글리피지드(glipizide) 및/또는 로시글리타존(rosiglitazone)와 함께 병용요법으로 사용할 수 있다. 본 발명의 펩티드 및 작용제는 SYMLIN®(프람린티드 아세테이트) 및 Exenatide®(합성 엑센딘-4; 39개 아미노산 펩티드)와 병용요법으로 사용할 수 있다.
또한, 본 발명의 펩티드 및 작용제는 수술후 장 폐색 치료를 위해 제제들(예, EnteregTM(알비모판; adolor/ ADL 8-2698), 커니밥탄(conivaptan) 및 미국 특허 6,645,959에 개시된 관련 제제)과 병용요법으로 사용될 수 있다.
본 발명의 펩티드 및 작용제는 하기 제제를 비제한적으로 포함하는 항고혈압제와 함께 병용요법으로 사용할 수 있다:
(1) 티아지드계와 같은 이뇨제, 예컨대 클로르탈리돈(chlorthalidone), 클로르티아지드(chlorthiazide), 디클로로펜아미드(dichiorophenamide), 하이드로플루메티아지드(hydrofinmethiazide), 인다파미드(indapamide), 폴리티아지드(polythiazide) 및 하이드로클로로티아지드; 부메타니드, 에트아크린산, 퓨로세미드(furosemide) 및 톨세미드와 같은 루프 이뇨제; 아밀로리드 및 트리암테렌(triamterene)과 같은 포타슘 스파링제(potassium sparing agent); 및 스피로노락톤, 에피레논 등과 같은 알도스테론 길항제;
(2) 아세부톨롤(acebutolol), 아테놀롤(atenolol), 베탁솔롤(betaxolol), 베반톨롤(bevantolol), 비소프롤롤(bisoprolol), 보핀돌롤(bopindolol), 카르테올롤(carteolol), 카르베딜롤(carvedilol), 셀리프롤롤(celiprolol), 에스몰롤(esmolol), 인데놀롤(indenolol), 메타프롤롤(metaprolol), 나돌롤(nadolol), 네비볼롤(nebivolol), 펜부톨롤(penbutolol), 핀돌롤(pindolol), 프로판올롤, 소탈롤(sotalol), 테르타톨롤(tertatobol), 틸리솔롤(tilisolol) 및 티콜롤(timolol) 등과 같은 베타-아드레날린성 차단제;
(3) 암로디핀(amlodipine), 아라니디핀(aranidipine), 아젤니디핀(azelnidipine), 바르니디핀(barnidipine), 베니디핀(benidipine), 베프리딜(bepridil), 신알디핀(cinaldipine), 클레비디핀(clevidipine), 딜티아젬(diltiazem), 에포니디핀(efonidipine), 펠로디핀(felodipine), 갈로파밀(galiopamil), 이스라디핀(isradipine), 락시디핀(lacidipine), 레밀디핀(lemildipine), 레르카니디핀(lercanidipine), 니카르디핀(nicardipine), 니페디핀(nifedipine), 닐바디핀(nilvadipine), 니모데핀(nimodepine), 니솔디핀(nisoidipine), 니트렌디핀(nitrendipine), 마니디핀(manidipine), 프라니디핀(pranidipine) 및 베라파밀(verapamil) 등과 같은 칼슘 채널 차단제;
(4) 베나제프릴(benazepril); 캡토프릴(captopril); 세라나프릴(ceranapril); 실라자프릴(cilazapril); 델라프릴(delapril); 에날라프릴(enalapril); 에날로프릴(enalopril); 포시노프릴(fosinopril); 이미다프릴(imidapril); 리시노프릴(lisinopril); 로시노프릴(losinopril); 모엑시프릴(moexipril); 퀴나프릴(quinapril); 퀴나프릴랫트(qninaprilat); 라미프릴(ramipril); 페린도프릴(perindopril); 페린드로프릴(perindropril); 쿼니프릴(quanipril); 스피라프릴(spirapril); 테노카프릴(tenocapril); 트란돌라프릴(trandoiapril) 및 조페노프릴(zofenopril) 등과 같은 안지오텐신 변환 효소(ACE);
(5) 오마파트릴랫트(omapatrilat), 카독사트릴(cadoxatril) 및 에카도트 릴(ecadotril), 포시도트릴(fosidotril), 삼파트릴랫트(sampatrilat), AVE7688, ER4030 등의 중성 엔도펩티다제 저해제;
(6) 테조센탄(tezosentan), A308165 및 YM62899 등의 엔도텔린 길항제;
(7) 하이드랄라진(hydralazine), 클로니딘(clonidine), 미녹시딜(minoxidil) 및 니코티닐 알콜(nicotinyl alcohol) 등의 혈관 확장제(vasodilator);
(8) 아프로사르탄(aprosartan), 칸데사르탄(candesartan), 에프로사르탄(eprosartan), 이르베사르탄(irbesartan), 리소사르탄(losartan), 올메사르탄(olmesartan), 프라토사르탄(pratosartan), 타소사르탄(tasosartan), 텔미사르탄(telmisartan), 발사르탄(valsartan), EXP-3137, FI6828K 및 RNH6270 등의 안지오텐신 II 수용체 길항제;
(9) 니프라딜롤(nipradilol), 아로티놀롤(arotinolol) 및 아모설랄롤(amosulabol) 등의 α/β 아드레날린성 차단제;
(10) 테라조신(terazosin), 유라피딜(urapidil), 프라조신(prazosin), 탐설로신(tamsulosin), 부나조신(bunazosin), 트리마조신(trimazosin), 독사조신(doxazosin), 나프토피딜(naftopidil), 인도라민(indoramin), WHP 164, 및 XEN010 등의 α 1 차단제;
(11) 로펙시딘(lofexidine), 티아메니딘(tiamenidine), 목소니딘(moxonidine), 릴메니딘(rilmenidine) 및 구아노벤즈 등의 α 1 작용제;
(12) 알도스테론 저해제 등; 및
(13) WO O3/030833에 개시된 것과 같은 안지오포이에틴-2-결합 제(angiopoietin-2-binding agent).
본 발명의 펩티드 및 작용제는 호흡성 질환 및 그외 질환 치료에 유용한 하기 제제 1종 이상과 함께 병용요법으로 사용될 수 있다.
(1) 이하를 비제한적으로 포함하는 베타-작용제: 알부테롤(PROVENTIL®, SALBUTAMO1®, VENTOLIN®), 밤부테롤(bambuterol), 비토테롤(bitoterol), 클렌부테롤(clenbuterol), 페노테롤(fenoterol), 포르모테롤(formoterol), 이소에타린(isoetharine)(BRONKOSOL®, BRONKOMETER®), 메타프로테레놀(metaproterenol)(ALUPENT®, METAPREL®), 피르부테롤(pirbuterol)(MAXAIR®), 레프로테롤(reproterol), 리미테롤(rimiterol), 살메테롤(salmeterol), 테르부탈린(terbutaline)(BRETHAIRE®, BRETH1NE®, BRICANYL®), 아드레날린, 이소프로테레놀(ISUPREL®), 에피네프린 비타르트레이트(epinephrine bitartrate)(PRIMATENE®), 에페드린(ephedrine), 오르시프렌린(orciprenline), 페노테롤(fenoterol) 및 이소에타린(isoetharine);
(2) 베클로메타손(becbomethasone), 베클로메타손 디프로피오네이트, 베타메타손(betamethasone), 부데소니드(budesonide), 부네도시드(bunedoside), 부틱소코르트(butixocort), 덱사메탄손(dexamethasone), 플루니솔리드(flunisolide), 플루오코ㄹ르르틴(fluocortin), 플루티카손(fluticasone), 하이드로코르티 손(hydrocortisone), 메틸 프레드니손(methyl prednisone), 모메타손(mometasone), 프레도니솔론(predonisolone), 프레도니손(predonisone), 티프레단(tipredane), 티속코르탈(tixocortal), 트리암시놀론(triamcinolone) 및 트리암시놀론 아세토니드(triamcinolone acetonide)를 비제한적으로 포함하는 스테로이드류;
(3) β2-작용제-코르티코스테로이드 조합물[예, 살메테롤(salmeterol)-플루티카손(fluticasone)(ADVAIR®), 포르모테롤-부데소니드(formoterol-budesonid) (SYMBICORT®)];
(4) 루코트리엔 D4 수용체 길항제/루코트리엔 길항제/LTD4 길항제(즉, 루코트리엔과 Cys LTI 수용체간의 상호작용을 차단, 저해, 감소 또는 방해할 수 있는 모든 화합물)로, 비제한적으로 자피르루카스트(zafirlukast), 몬테루카스트(montelukast), 몬테루카스트 소듐 (SINGULAIR®), 프란루카스트, 이라루카스트, 포비루카스트, SKB-106,203 및 미국 특허 5,565,473에 개시된 LTD4 길항성 활성을 가지는 것으로 확인된 화합물들);
(5) 5-리폭시게나제 저해제 및/또는 루코트리엔 생합성 저해제[예, 질루톤(zileuton) 및 BAY1005 (CA registry 128253-31-6)];
(6) 히스타민 Hl 수용체 길항제/항히스타민제(즉, 히스타민과 그것의 수용체간의 상호작용을 차단, 저해, 감소 또는 방해할 수 있는 모든 화합물)로, 비제한적으로 아스테미졸(astemizole), 아크리바스틴(acrivastine), 안타졸린(antazoline), 아자타딘(azatadine), 아젤라스틴(azelastine), 아스타미졸(astamizole), 브로모페 니라민(bromopheniramine), 브로모페니라민 말레이트(bromopheniramine maleate), 카르비녹사민(carbinoxamine), 케르바스틴(carebastine), 세티리진(cetirizine), 클로르페니라민(chlorpheniramine), 클로로페니라민 말레이트, 시메티딘(cimetidine), 클레마스틴(clemastine), 사이클리진(cyclizine), 사이프로헵타딘(cyproheptadine), 데스카르보에톡실로라타딘(descarboethoxyloratadine), 엑스클로르페니라민(dexchlorpheniramine), 디메틴덴(dimethindene), 디페닐하이드라민(diphenhydramine), 디페닐피랄린(diphenylpyraline), 독시라민 숙시네이트(doxylamine succinate), 독실라르닌(doxylarnine), 에바스틴(ebastine), 에플레티리진(efletirizine), 에피나스틴(epinastine), 파르노티딘(famotidine), 펙소페나딘(fexofenadine), 하이드록시진(hydroxyzine), 하이드록시진(hydroxyzine), 케토티펜(ketotifen), 레보카바스틴(levocabastine), 레보세티리진(levocetirizine), 레보세티리진(levocetirizine), 로라타딘(loratadine), 메클리진(meclizine), 메피라민(mepyramine), 메퀴타진(mequitazine), 메트딜라진(methdilazine), 미안세린(mianserin), 미졸라스틴(mizolastine), 노베라스틴(noberastine), 노라스테르니졸(norasternizole), 노라즈테니졸(noraztemizole), 페닌다민(phenindamine), 페니라민(pheniramine), 피쿠마스트(picumast), 프로메타진(promethazine), 핀늘라민(pynlamine), 피릴라민(pyrilamine), 라니티딘(ranitidine), 테멜라스틴(temelastine), 테르페나딘(terfenadine), 트리메프라진(trimeprazine), 트리펠레나민(tripelenamine), 및 트리프롤리딘(triprolidine);
(7) 아트로핀(atropine), 벤즈트로핀(benztropine), 비페리딘(biperiden), 플루트로피움(flutropium), 히오시아민(hyoscyamine), 일루트로피움(ilutropium), 이프라트로피움(ipratropium), 이프라트로피움 브로마이드, 메트스코폴아민(methscopolamine), 옥시부티닌(oxybutinin), 리스펜제핀(rispenzepine), 스코폴아민(scopolamine), 및 티오트로피움(tiotropium)을 비제한적으로 포함하는 항콜린제(anticholinergic);
(8) 덱스트로메토르판(dextromethorphan), 코데인(codeine), 및 하이드로모르폰(hydromorphone)을 비제한적으로 포함하는 진해제(anti-tussive);
(9) 슈도에페드린(pseudoephedrine) 및 페닐프로파놀아민을 비제한적으로 포함하는 충혈 완화제(decongestant);
(10) 구아페네신(guaifenesin), 구아이콜설페이트(guaicolsulfate), 테르핀(terpin), 암모늄 클로라이드, 글리세롤 구아이콜레이트 및 요오드화 글리세롤을 비제한 적으로 포함하는 거담제(expectorant);
(11) 테오필린(theophylline) 및 아미노필린(aminophylline)을 비제한적으로 포함하는 기관지 확장제(bronchodilator);
(12) 플루리비프로펜(fluribiprofen), 디클로페낙(diclophenac), 인도메타신(indomethacin), 케토프로펜(ketoprofen), S-케트로프로펜(S-ketroprophen), 테녹시캄(tenoxicam)을 비제한적으로 포함하는 항염증제;
(13) 본 명세서에 기재된 것을 비제한적으로 포함하는 PDE(포스포다이에스테라제) 저해제;
(14) 인간화된 재조합 다일클론 항체(예, 솔레어(xolair)(오말리주 맵(omalizumab)), rhuMab 및 탈리주맵(talizumab));
(15) 재조합 형태의 계면활성제 단백질 SP-B, SP-C 또는 SP-D (예, SURFAXIN®, dsc-104(Discovery Laboratories))를 포함하는 인간화된 폐 계면활성제;
(16) 아밀로리드 및 관련 화합물과 같은 상피 소듐 채널(ENaC) 저해제;
(17) 어사이클로비어(acyclovir), 아미카신(amikacin), 아목시실린(amoxicillin), 독시사이클린(doxycycline), 트리메토프린 설파메톡사졸(trimethoprin sulfamethoxazole), 암포테리신B(amphotericin B), 아지트로마이신(azithromycin), 클라리트로마이신(clarithromycin), 록시트로마이신(roxithromycin), 클라리트로마이신(clarithromycin), 세팔로스포린(cephalosporin)(세폭시틴(ceffoxitin), 세프메타졸(cefmetazole) 등), 시프로플록사신(ciprofloxacin), 에탐부톨(ethambutol), 젠티마이신(gentimycin), 간시클로비어(ganciclovir), 이미페넴(imipenem), 이소니아지드(isoniazid), 이트라코나졸(itraconazole), 페니실린, 리바비린(ribavirin), 리팜핀(rifampin), 리파부틴(rifabutin), 아만타딘(amantadine), 리만티딘(rimantidine), 스트렙토마이신, 토브라마이신(tobramycin), 및 반코마이신(vancomycin)과 같은 폐 감염증 치료에 사용되는 항미생물제;
(18) Ca++ 의존성 클로라이드 채널을 통해 클로라이드 배출을 활성화하는 제제(예컨대, 퓨린 수용체(purinergic receptor)(P2Y(2) 작용제));
(19) 인간 재조합 DNase1(Pulmozyme®)과 같은 객담 점도를 저하시키는 제 제;
(20) 비스테로이드성 항염증제(아세메타신(acemetacin), 아세타미노펜(acetaminophen), 아세틸 살리사이클릭산(acetyl salicylic acid), 알클로페낙(alclofenac), 알미노프로펜(alminoprofen), 아파존(apazone), 아스피린, 베녹사프로펜(benoxaprofen), 베즈피페릴론(bezpiperylon), 부클록식산(bucloxic acid), 카르프로펜(carprofen), 클리다낙(clidanac), 디클로페낙(diclofenac), 디플루니살(diflunisal), 디플루시날(diflusinal), 에토돌락(etodolac), 펜부펜(fenbufen), 펜클로페낙(fenclofenac), 펜클로직산(fenclozic acid), 페노프로펜(fenoprofen), 펜티아작(fentiazac), 페프라존(feprazone), 플루페남산(flufenamic acid), 플루페니살(flufenisal), 플루프로펜(fluprofen), 플루비프로펜(flurbiprofen), 플루르비프로펜(flurbiprofen), 퓨로페낙(furofenac), 이부페낙(ibufenac), 이부프루펜(ibuprofen), 인도메타신(indomethacin), 인도프로펜(indoprofen), 이속세팍(isoxepac), 이속시캄(isoxicam), 케토프로펜(ketoprofen), 케토롤락(ketorolac), 메클로펜암산(meclofenamic acid), 메펜암산(mefenamic acid), 미로프로펜(miroprofen), 모페부타존(mofebutazone), 나부메톤 옥사프로진(nabumetone oxaprozin), 나프록센(naproxen), 니플룸산(niflumic acid), 옥사프로진(oxaprozin), 옥피낙(oxpinac), 옥시펜부타존(oxyphenbutazone), 펜아세틴(phenacetin), 페닐부타존(phenylbutazone), 피록시캄(piroxicam), 피르프로펜(pirprofen), 프라노프로펜(pranoprofen), 슈독시캄(sudoxicam), 테녹시캄(tenoxican), 설파살라진(sulfasalazine), 설린닥(sulindac), 슈프로 펜(suprofen), 티아프로펜산(tiaprofenic acid), 티오피낙(tiopinac), 티옥사프로펜(tioxaprofen), 톨펜암산(tolfenamic acid), 톨메틴(tolmetin), 지도메타신(zidometacin), 및 조메피락(zomepirac));
(21) S-니트로소글루타티온과 같은 에어로졸형의 항산화 치료제.
본 발명의 펩티드 및 작용제는 하기를 비제한적으로 포함하는 항비만제와 병용요법으로 사용할 수 있다:
(1) BVT 3498, BVT 2733, 3-(l-아다만틸)-4-에틸-5-(에틸 티오)-4H-1,2,4-트리아졸, 3-(1-아다만틸)-5-(3,4,5-트리메톡시페닐)-4-메틸-4H-1,2,4-트리아졸, 3-아다만타닐-4,5,6,7,8,9,10,11,12,3a-데카하이드로-1,2,4-트리아졸로[4,3-a][11]아눌렌, 및 WO 01/90091, WO 01/90090, WO 01/90092와 WO 02/072084에 기재된 화합물과 같은 11/β HSD-I (11-beta hydroxy steroid dehydrogenase type 1) 저해제;
(2) 파록세틴(paroxetine), 플루옥세틸(fluoxetine)(Prozac®), 펜플루라민(fenfluramine), 플루복사민(fluvoxamine), 세르트랄린(sertraline), 및 이미프라민(imipramine)과 같은 5HT(세로토닌) 수송체 저해제 및 WO 03/00663에 기재된 화합물;
(3) WO 03/037871, WO 03/037887 등에 기재된 5HT 길항제
(4) WWO 03/031439 등에 기재된 5HT 1a 모듈레이터;
(5) 5HT-2 작용제;
(6) BVT933, DPCA37215, IK264, PNU 22394, WAY161503, R-1065, SB 2432(Glaxo Smith Kline) 및 YM348과 미국 특허 3,914,250, WO 02/36596, WO 02/48124, WO 02/10169, WO 01/66548, WO 02/44152, WO 02/51844, WO 02/40456 및 WO 02/40457에 개시된 것과 같은 5HT2c(세로토닌 수용체 2c) 작용제;
(7) WO 03/030901, WO 03/035061, WO 03/039547 등에 개시된 5HT6 수용체 모듈레이터;
(8) ACC2 (acetyl-CoA carboxylase-2) 저해제;
(9) del Mar-Grasa, M. et al., Obesity Research, 9:202-9 (2001) 및 일본 특허 출원 JP 2000256190에 개시된 올레오일-에스트론(oleoyl-estrone)과 같은 아실-에스트로겐류(acyl-estrogen);
(10) 알파-리폭익산(알파-LA);
(11) 1426(Aventis) 및 1954(Aventis)와 같은 식욕 감퇴성 이환성 화합물(anorectic bicyclic compound) 및 WO 00/18749, WO 01/32638, WO 01/62746, WO 01/62747, 및 WO 03/015769에 개시된 화합물;
(12) AOD9604;
(13) WO 03/40107에 개시된 것과 같은 식욕 억제제;
(14) ATL-962 (Alizyme PLC);
(15) 벤조카인(benzocaine);
(16) 벤즈페타민 하이드로클로라이드(benzphetamine hydrochloride)(Didrex);
(17) 블래더랙(bladderwrack)(focus vesiculosus);
(18) BRS3(봄베신(bombesin) 수용체 서브타입 3) 작용제;
(19) 부프로피온(bupropion);
(20) 카페인;
(21) 리모나반트(rimonabant)(Acomplia; Sanofi Synthelabo), SR-147778(Sanofi Synthelabo), BAY 65-2520(Bayer) 및 SLV 319(Solvay), 및 US 특허 4,973,587, 5,013,837, 5,081,122, 5,112,820, 5,292,736, 5,532,237, 5,624,941, 6,028,084, 6,509,367, WO 96/33159, WO 97/29079, WO 98/31227, WO 98/33765, WO 98/37061, WO 98/41519, WO 98/43635, WO 98/43636, WO 99/02499, WO 00/10967, WO 00/10968, WO 01/09120, WO 01/58869, WO 01/64632, WO 01/64633, WO 01/64634, WO 01/70700, WO 01/96330, WO 02/076949, WO 03/006007, WO 03/007887, WO 03/020217, WO 03/026647, WO 03/026648, WO 03/027069, WO 03/027076, WO 03/027114, WO 03/037332, WO 03/040107, WO 03/086940, WO 03/084943, 미국 특허 6,509,367 및 EP-658546에 개시된 것과 같은, CB 1(카나비노이드(cannabinoid)-1 수용체) 길항제/역 작용제;
(22) CCK 작용제;
(23) AR-R 15849, GI 181771, JMV-180, A-71378, A-71623, SR146131, 미국 특허 5,739,106에 개시된 것과 같은 CCK-A(클로레사이스토키닌(cholecystokinin)-A) 작용제;
(24) 키토산;
(25) 크로뮴;
(26) GI-181771(Glaxo-Smith Kline), SR146131(Sanofi Synthelabo), 부타빈디드(butabindide), PD170,292, 및 PD 149164 (Pfizer)과 같은, CNTF(Ciliary neurotrophic factors),;
(27) 악소킨(axokine)(Regeneron)과 WO 94/09134, WO 98/22128 및 WO 99/43813에 개시된 것과 같은 CNTF 유도체;
(28) 접합된 리놀레익산(conjugated linoleic acid);
(29) 코르티코트로핀-방출 호르몬(corticotropin-releasing hormone) 작용제;
(30) 디하이드로에피안드로스테론(dehydroepiandrosterone);
(31) DGATl(diacylglycerol acyltransferase 1) 저해제;
(32) DGAT2(diacylglycerol acyltransferase 2) 저해제;
(33) 디카르복실레이트 수송체 저해제(dicarboxylate transporter inhibitor);
(34) 디에틸프로피온 하이드로클로라이드(diethylpropion hydrochloride)(Tenuate);
(35) 이소루신 티아졸리디드(isoleucine thiazolidide), 발린 피롤리디드(valine pyrrolidide), NVP-DPP728, LAF237, P93/01, TSL 225, TMC-2A/2B/2C, FE 999011, P9310/K364, VIP 0177, SDZ 274-444 및 WO 02/083128, WO 02/062764, WO 03/000180, WO 03/000181, WO 03/000250, WO 03/002530, WO 03/002531, WO 03/002553, WO 03/002593, WO 03/004498, WO 03/004496, WO03/017936, WO 03/024942, WO 03/024965, WO 03/033524, WO 03/037327와 EP1258476에 개시된 화합물과 같은 디펩티딜 펩티다제 IV (DP-IV) 저해제;
(36) 에페드라(ephedra);
(37) 엑센딘(exendin)-4(glp-1 저해제);
(38) 세룰레닌(Cerulenin) 및 C75과 같은 FAS(fatty acid synthase) 저해제;
(39) WO 03/053451 등에 기재된 지방 재흡수 저해제;
(40) 지방산 수송체 저해제;
(41) 섬유(실리엄(psyllium), 플란타고(plantago), 구아 섬유)
(42) 갈라닌(galanin) 길항제;
(43) 갈레가(galega)(Goat's Rue, French Lilac);
(44) 가르시니아 캄보기아(garcinia cambogia);
(45) 게르만더(germander)(teucrium chamaedrys);
(46) 그렐린 길항제, 예컨대 WO 01/87335와 WO 02/08250에 개시된 화합물;
(47) GLP-I(glucagon-like peptide 1) 작용제 (예, 엑센딘-4);
(48) glp-1(glucagon-like peptide-1);
(49) 글루코코르티코이드 길항제;
(50) 글루코스 수송체 저해제;
(51) 성장 호르몬 분비 촉진(growth hormone secretagogue) 수용체 작용제/길항제, 예, NN703, 헥사렉린(hexarelin), MK-0677, SM-130686, CP-424,391, L-692,429, L-163,255, 미국 특허 6,358,951, 미국 출원번호 2002/049196 및 2002/022637, WO 01/56592 및 WO 02/32888에 개시된 것;
(52) 성장 호르몬 분비 촉진제, 예컨대, 미국 특허 5,536,716에 개시되고 구체적으로 설명된 것;
(53) 티오페르아미드(thioperamide), 3-(lH-이미다졸-4-일)프로필 N-(4-펜테닐)카르바메이트), 클로벤프로피트(clobenpropit), 요오도펜프로피트(iodophenpropit), 이모프록시판(imoproxifan), GT2394(Gliatech), A331440, WO 02/15905에 개시된 것, O-[3-(lH-이미다졸-4-일)프로판올]카바메이트(Kiec-Kononowicz, K. et al., Pharmazie, 55:349-55 (2000)), 피페리딘 함유 히스타민 H3-수용체 길항제(Lazewska, D. et al., Pharmazie, 56:927-32 (2001)), 벤조페논 유도체 및 관련 화합물들(Sasse, A. et al., Arch. Pharm.(Weinheim) 334:45-52 (2001)), 치환된 N-페닐카바메이트(Reidemeister, S. et al., Pharmazie, 55:83-6 (2000)), 프록시판 유도체(Sasse, A. et al., J. Med. Chem.. 43:3335-43 (2000))와 같은 H3 (histamine H3) 길항제/역 작용제, 및 WO 03/024928와 WO 03/024929에 개시된 것과 같은 히스타민 H3 수용체 모듈레이터;
(54) WO 03/057237 등에 기재된 바와 같은 인터루킨-6(IL-6) 및 그의 모듈레이터;
(55) L-카르니틴;
(56) 렙틴 유도체들, 예컨대, 미국 특허 5,552,524, 5,552,523, 5,552,522, 5,521,283, WO 96/23513, WO 96/23514, WO 96/23515, WO 96/23516, WO 96/23517, WO 96/23518, WO 96/23519, 및 WO 96/23520에 개시된 것;
(57) 재조합 인간 렙틴(PEG-OB, Hoffman La Roche) 및 재조합 메티오닐 인간 렙틴(Amgen)을 포함하는 렙틴;
(58) 테트라하이드로립스타틴(tetrahydrolipstatin)(orlistat/Xenical®), 트리톤 WRl339, RHC80267, 립스타틴, 티사포닌(teasaponin), 디에틸룸벨리페릴 포스페이트(diethylumbelliferyl phosphate), FL-386, WAY-121898, Bay-N-3176, 발리락톤(valilactone), 에스테락신(esteracin), 에벨락톤(ebelactone) A, 에벨락톤 B, RHC 80267, 및 WO 01/77094, 미국 특허 4,598,089, 4,452,813, 5,512,565, 5,391,571, 5,602,151, 4,405,644, 4,189,438, 및 4,242,453에 기재된 것과 같은 리파제 저해제;
(59) 마슬린산(maslinic acid), 에리트로디올(erythrodiol), 우르솔산(ursolic acid), 유바올(uvaol), 베툴린산(betulinic acid), 베툴린(betulin) 등과 WO 03/011267에 개시된 것과 같은 지질 대사 모듈레이터;
(60) Mc3r (멜라노코르틴 3 수용체) 작용제;
(61) CHIR86036(Chiron), ME-10142, ME-10145, HS-131(Melacure) 및 WO 99/64002, WO 00/74679, WO 01/991752, WO 01/25192, WO 01/52880, WO 01/74844, WO 01/70708, WO 01/70337, WO 01/91752, WO 02/059095, WO 02/059107, WO 02/059108, WO 02/059117, WO 02/06276, WO 02/12166, WO 02/11715, WO 02/12178, WO 02/15909, WO 02/38544, WO 02/068387, WO 02/068388, WO 02/067869, WO 02/081430, WO 03/06604, WO 03/007949, WO 03/009847, WO 03/009850, WO 03/013509,및 WO 03/031410에 개시된 것과 같은 Mc4r(멜로노코르틴 4 수용체) 작용제;
(62) WO 97/19952, WO 00/15826, WO 00/15790, US 20030092041에 개시된 것과 같은 Mc5r(멜라노코르틴 5 수용체) 모듈레이터;
(63) MCH2R(멜라틴 농축 호르몬 2R) 작용제/길항제;
(64) 멜라닌 농축 호르몬 길항제;
(65) T-226296(Takeda), SNP-7941(Synaptic) 및 WO 01/21169, WO 01/82925, WO 01/87834, WO 02/051809, WO 02/06245, WO 02/076929, WO 02/076947, WO 02/04433, WO 02/51809, WO 02/083134, WO 02/094799, WO 03/004027, WO 03/13574, WO 03/15769, WO 03/028641, WO 03/035624, WO 03/033476, WO 03/033480, JP 13226269와 JP1437059에 개시된 것과 같은 멜라닌 농축 호르몬 1 수용체(MCHR) 길항제;
(66) Melanotan II 또는 WO 99/64002와 WO 00/74679에 개시된 것과 같은 멜라노코르틴 작용제;
(67) 메트폴르민(Metformin)(GLUCOPHAGE®);
(68) WO 03/029210, WO 03/047581, WO 03/048137, WO 03/051315, WO 03/051833, WO 03/053922, WO 03/059904 등에 개시된 것과 같은 mGluR5 모듈레이터;
(69) 시부트라트민(sibutratmine)(Meridia®/Reductil®) 및 그의 염과 미국 특허 4,746,680, 4,806,570, 5,436,272, 미국 특허 2002/0006964, WO 01/27068, WO 01/62341에 개시된 화합물과 같은, 모노아민 재흡수 저해제;
(70) GW 320659, 데스피라민(despiramine), 탈서프람(talsupram) 및 노미펜신(nomifensine)과 같은 NE(노레핀에프린) 수송체 저해제;
(71) 노만 허바(nomame herba);
(72) 시부트라민 또는 펜플루라민과 같은 비선택적 세로토닌/노레핀에프린 수송체 저해제;
(73) BIBP3226, J-115814, BIBO 3304, LY-357897, CP-671906, GI-264879A와 미국 특허 6,001,836, WO 96/14307, WO 01/23387, WO 99/51600, WO 01/85690, WO 01/85098, WO 01/85173 및 WO 01/89528에 개시된 것과 같은 NPY1 길항제;
(74) 152,804, GW-569180A, GW-594884A, GW-587081X, GW-548118X, FR235208, FR226928, FR240662, FR252384, 1229U91, GI-264879A, CGP71683A, LY-377897, LY-366377, PD-160170, SR-120562A, SR-120819A, JCF-104, H409/22, 및 미국 특허 6,140,354, 6,191,160, 6,258,837, 6,313,298, 6,326,375, 6,329,395, 6,335,345, 6,337,332, 6,329,395, 6,340,683, EP-01010691, EP-01044970, WO 97/19682, WO 97/20820, WO 97/20821, WO 97/20822, WO 97/20823, WO 98/27063, WO 00/107409, WOOO/185714, WOOO/185730, WO 00/64880, WO 00/68197, WO 00/69849, WO 01/09120, WO 01/14376, WO 01/85714, WO 01/85730, WO 01/07409, WO 01/02379, WO 01/23388, WO 01/23389, WO 01/44201, WO 01/62737, WO 01/62738, WO 01/09120, WO 02/20488, WO 02/22592, WO 02/48152, WO 02/49648, WO 02/051806, WO 02/094789, WO 03/009845, WO 03/014083, WO 03/022849, WO 03/028726, Norman et al, J. Med. Chem. 43:4288-4312 (2000)에 개시된 화합물과 같은, NPY5(뉴로펩티드 Y Y5) 길항제;
(75) 날메핀(nalmefene)(REVEX®), 3-메톡시날트렉손, 날록손(naloxone), 날트렉손 및 WO 00/21509에 개시된 화합물과 같은 오피오이드 길항제;
(76) SB-334867-A 및 WO 01/96302, WO 01/68609, WO 02/44172, WO 02/51232, WO 02/51838, WO 02/089800, WO 02/090355, WO 03/023561, WO 03/032991, 및 WO 03/037847에 개시된 화합물과 같은 오렉신(orexin) 길항제;
(77) 본원에 기재된 것을 비제한적으로 포함하는 PDE(phosphodiesterase) 저해제;
(78) 펩티드 YY 및 그의 변이체와 절편(예, YY3-36 (PYY3-36)(N. Engl. J. Med. 349:941, 2003; IKPEAPGE DASPEELNRY YASLRHYLNL VTRQRY (서열번호 XXX)) 및 WO 03/026591에 개시된 화합물과 같은 PYY 작용제;
(79) 펜디메트라진(phendimetrazine);
(80) 펜테르민(phentermine);
(81) 포스페이트 수송체 저해제;
(82) 포스포디에스테라제-3B (PDE3B) 저해제;
(83) 피토팜(phytopharm) 화합물 57(CP 644,673);
(84) 피루베이트;
(85) SCD-1(스테아로일-CoA 디세투라제(desaturase)-1) 저해제;
(86) 덱스펜플루라민, 플루옥세틴 및 미국 특허 6,365,633, WO O1/27060와 WO 01/162341에 개시된 화합물과 같은 세로토닌 재흡수 저해제;
(87) T71(Tularik Inc; Boulder CO);
(88) KB-2611(KaroBioBMS) 및 WO 02/15845와 JP 2000256190에 개시된 화합물과 같은 갑상선 호르몬 β 작용제;
(89) 토피라메이트(Topiramate)(TOPMAX®);
(90) WO 03/026576에 개시된 화합물과 같은 전사 인자 모듈레이터;
(91) 피탄산(phytanic acid), 4-[(E)-2-(5,6,7,8-테트라하이드로-5,5,8,8-테트라메틸-2-나프탈레닐)-1-프로페니-1]-벤조산(TTNPB), 레티노익산 및 WO 99/00123에 개시된 화합물과 같은 UCP-1 (uncoupling ρrotein-1), 2, 또는 3 활성화제;
(92) AD9677/TAK677(Dainippon/Takeda), CL-316,243, SB 418790, BRL-37344, L-796568, BMS-196085, BRL-35135A, CGP12177A, BTA-243, GW 427353, 트레카드린(Trecadrine), 제네카(Zeneca) D7114, N-5984(Nisshin Kyorin), LY-377604(Lilly), SR 59119A, 및 미국 특허 5,705,515, 미국 특허 5,451,677, WO 94/18161, WO 95/29159, WO 97/46556, WO 98/04526 and WO 98/32753, WO 01/74782, WO 02/32897, WO 03/014113, WO 03/016276, WO 03/016307, WO 03/024948, WO 03/024953 및 WO 03/037881에 개시된 화합물과 같은 β3(베타 아드레날린성 수용체 3) 작용제;
(93) β-하이드록시 스테로이드 디하이드로게나제-1 저해제(β-HSD-I); 및
(94) β-하이드록시-β-메틸부티레이트.
비만 치료에 유용한 본 발명의 펩티드 및 작용체는 전기자극과 공동요법으로 투여할 수 있다(미국 특허 20040015201).
본 발명의 펩티드 및 작용제는 가용성 구아닐레이트 사이클라제, 예컨대 미국 특허 20040192680에 개시된 제제와 병용요법으로 사용할 수 있다.
본 발명의 펩티드 및 작용제는 포스포디에스테라제 저해제와 병용요법으로 사용할 수 있다. 본 발명에 포함되는 PDE 저해제는, 포스포디에스테라제의 저해에 의해 환형 AMP (cAMP)및/또는 환형 GMP(cGMP)의 분해를 서행시켜, 세포내 cAMP 및 cGMP의 농도를 상대적으로 증가시킬 수 있는 화합물이다. 본 발명에 포함가능한 PDE 저해제는 일차적으로 PDE3 저해제로 구성된 클래스, PDE4 저해제로 구성된 클래스 및/또는 PDE5 저해제로 구성된 클래스들 중에서, 특히 PDE3/4 저해제의 혼합형이나 PDE3/4/5 저해제들의 혼합물으로 명시할 수 있는 물질들에 포함되는 물질이다. 예컨대, 이러한 PDE 저해제는 하기 특허 출원 및 특허들에 개시 및/또는 첨부된 것으로 언급할 수 있다: DE1470341, DE2108438, DE2123328, DE2305339, DE2305575, DE2315801, DE2402908, DE2413935, DE2451417, DE2459090, DE2646469, DE2727481, DE2825048, DE2837161, DE2845220, DE2847621, DE2934747, DE3021792, DE3038166, DE3044568, EP000718, EP0008408, EP0010759, EP0059948, EP0075436, EP0096517, EPOl 12987, EPOl 16948, EP0150937, EP0158380, EP0161632, EP0161918, EP0167121, EP0199127, EP0220044, EP0247725, EP0258191, EP0272910, EP0272914, EP0294647, EP0300726, EP0335386, EP0357788, EP0389282, EP0406958, EP0426180, EP0428302, EP0435811, EP0470805, EP0482208, EP0490823, EP0506194, EP0511865, EP0527117, EP0626939, EP0664289, EP0671389, EP0685474, EP0685475, EP0685479, JP92234389, JP94329652, JP95010875, 미국 특허 4,963,561, 5,141,931, WO 9117991, WO 9200968, WO 9212961, WO 9307146, WO 9315044, WO 9315045, WO 9318024, WO 9319068, WO 9319720, WO 9319747, WO 9319749, WO 9319751, WO 9325517, WO 9402465, WO 9406423, WO 9412461, WO 9420455, WO 9422852, WO 9425437, WO 9427947, WO 9500516, WO 9501980, WO 9503794, WO 9504045, WO 9504046, WO 9505386, WO 9508534, WO 9509623, WO 9509624, WO 9509627, WO 9509836, WO 9514667, WO 9514680, WO 9514681, WO 9517392, WO 9517399, WO 9519362, WO 9522520, WO 9524381, WO 9527692, WO 9528926, WO 9535281, WO 9535282, WO 9600218, WO 9601825, WO 9602541, WO 9611917, DE3142982, DEl 116676, DE2162096, EP0293063, EP0463756, EP0482208, EP0579496, EP0667345 미국 특허 6,331,543, 미국 특허 20050004222 (식 XIII 및 단락 37-39, 85-0545 및 557-577에 개시된 사항 포함), 및 WO 9307124, EP0163965, EP0393500, EP0510562, EP0553174, WO 9501338 및 WO 9603399. 예로 언급할 수 있는 PDE5 저해제로는, RX-RA-69, SCH-51866, KT-734, 베스나리논(vesnarinone), 자프리나스트(zaprinast), SKF-96231, ER-21355, BF/GP-385, NM-702 및 실데나필(sildenafil) (Viagra®)이 있다. 예로 언급할 수 있는 PDE4 저해제로는 RO-20-1724, MEM 1414 (R1533/R1500; Pharmacia Roche), 덴부필린(DENBUFYLLINE), 롤리프람(ROLIPRAM), 옥사프렐레이트(OXAGRELATE), 니트라쿼존(NITRAQUAZONE), Y-590, DH-6471, SKF-94120, 모타피존(MOTAPIZONE), 릭사지논(LIXAZINONE), 인돌리단(INDOLIDAN), 올프리논(OLPRINONE), 아티조람(ATIZORAM), KS-506-G, 디팜필린(DIPAMFYLLINE), BMY-43351, 아티조람(ATIZORAM), 아로필린(AROFYLLINE), 필라미나스트(FILAMINAST), PDB-093, UCB-29646, CDP-840, SKF-107806, 피클라미라스트(PICLAMILAST), RS-17597, RS-25344-000, SB-207499, 티벤라스트(TIBENELAST), SB-210667, SB-211572, SB-211600, SB-212066, SB-212179, GW-3600, CDP-840, 모피다몰(MOPIDAMOL), 아나그렐리드(ANAGRELIDE), 이부딜라스트(IBUDILAST), 암리논(AMRINONE), 피모벤단(PIMOBEND AN), 킬로스타졸(CILOSTAZOL), 쿼지논(QUAZINONE) 및 N-(3,5-디클로로피리드-4-일)-3-사이클로프로필메톡시 4-디플루오로메톡시벤즈아미드가 있다. 예로 언급할 수 있는 PDE3 저해제로는, 설마졸(SULMAZOLE), 암피존(AMPIZONE), 킬로스타미드(CILOSTAMIDE), 카르바제란(CARBAZERAN), 피록시몬(PIROXIMONE), 이마조단(IMAZODAN), CI-930, 시구아조단(SIGUAZODAN), 아디벤단(ADIBENDAN), 사테리논(SATERINONE), SKF-95654, SDZ-MKS-492, 349-U-85, 에모라단(EMORADAN), EMD-53998, EMD-57033, NSP-306, NSP-307, 레비지논(REVIZINONE), NM-702, WIN-62582, WIN-63291, 에녹시몬(ENOXIMONE) 및 밀리논(MILRINONE)이 있다. 예로 언급할 수 있는 PDE3/4 저해제로는, 베나펜트린(BENAFENTRINE), 트리퀸신(TREQUINSIN), ORG-30029, 자르다베린(ZARDAVERINE), L-686398, SDZ-ISQ-844, ORG-20241, EMD-54622 및 톨라펜트린(TOLAFENTRINE)이 있다. 그외 PDE 저해제로는, 킬로밀라스 트(cilomilast), 펜톡시필린(pentoxifylline), 로플루밀라스트(roflumilast), 타달라필(tadalafil)(Cialis®), 티오필린(theophylline), 바르데나필(vardenafil)(Levitra®), 및 자프리나스트(zaprinast)(PDE5 특이적)가 있다.
치료 방법
다수의 질환들은 본 발명의 펩티드 및 작용제를 포함하는 cGMP 수준을 증가시키는 GC-C 수용체 작용제 및 제제로 치료된다.
본 발명의 펩티드 및 작용제는 울혈성 심부전증의 치료 또는 예방에 있어서 단독으로 또는 병용 치료요법으로 사용할 수 있다. 이러한 제제는 나트륨 이뇨 펩티드(natriuretic peptide)(예, 심방성 나트륨 이뇨 펩타이(atrial natriuretic peptide), 뇌성 나트륨 이뇨 펩티드(brain natriuretic peptide), C형 나트륨 이뇨 펩티드), 이뇨제 또는 안지오텐신 전환 효소 저해제와 함께 병용하여 사용할 수 있다.
본 발명의 펩티드 및 작용제는 양성 전립선 비대증(BPH)의 치료 또는 예방에 있어서 단독으로 또는 병용 치료요법으로 사용할 수 있다. 이러한 제제는 1종 이상의 BPH 치료제 예컨대 5-알파 리덕타아제 저해제(예, 피나스테리드) 또는 알파 아드레날린성 저해제(예, 독사조신)와 병용 투여할 수 있다.
본 발명의 펩티드 및 작용제는 위장병 관련 내장 통증이나 그외 질병 관련 통증을 치료, 예방 또는 완화시키기 위해 단독으로 또는 병용 치료요법으로 사용할 수 있다.
본 발명의 펩티드 및 작용제는 비관 관련 질환(예, 비만과 관련된 질환, 비만이 원인인 질환 또는 비만의 결과로서 발생되는 질환)의 치료 또는 예방에 있어서 단독으로 또는 병용 치료요법으로 사용할 수 있다. 비만 관련 질환의 예로는, 과식 및 이상 식욕 항진증, 고혈압, 당뇨병, 혈중 인슐린 농도 증가, 인슐린 저항성 증가, 이상지혈증(dyslipidemias), 고지혈증, 자궁내막암, 유방암, 전립선암, 결장암, 골관절염, 폐색성 수면 모호흡증(obstructive sleep apnea), 담석증, 담석, 심장병, 심장 리듬 이상증(abnormal heart rhythm), 부정맥, 심근 경색, 울혈성 심부전증, 관상 동맥 질환, 급사, 발작, 다낭성 난소 질환(polycystic ovarian disease), 두개인두종(craniopharyngioma), 프레더-윌리 증후군, 프롤리히 증후군, GH-결핍성 개체, 저신장증의 정상적 변형(normal variant short stature), 터너 증후군, 및 그외 대사 활성 감소 또는 총 제지방량(fat-free mass) 퍼센트로서 기초 에너지 대사량(resting energy expenditure) 감소를 보이는 그외 병리학상 증상, 예컨대 급성 림프성아구성 백혈병(acute lymphoblastic leukemia)이 있다. 본 발명의 제제는 체중(또는 지방)을 감소 또는 조절하거나, 비만 또는 그외 식품, 에탄올 및 그외 식욕을 돋우는 물질의 과식과 관련된 그외 식욕 관련 질환의 예방 및/또는 치료하기 위해 사용할 수 있다. 제제는, 지질 대사를 조절하고, 체지방을 낮추고(예, 지방 사용을 증가시켜), 또는 식욕을 감소(또는 억제)하기(예, 포만감 유도) 위해 사용할 수 있다. 또다른 비만 관련 질환의 예로는, 증후군 X로 알려져 있는 대사성 증후군, 인슐린 내성 증후군, 불임, 남성의 생식선기능저하증(hypogonadism) 및 여성의 다모증과 같은 성 및 생식 기능 장애(sexual and reproductive dysfunction), 비만 관련 위-식도 역류와 같은 위장 운동 장애, 비만-저환기 증후군(피크위크 증후군)과 같은 호흡기 질환, 심혈관 질환, 맥관(vasculature)의 전신성 염증과 같은 염증, 동맥경화증, 고콜레스테롤혈증, 고뇨산 혈증, 하요통(lower back pain), 담낭 질환, 통풍(gout) 및 신장암이 있다. 본 발명의 제제는 또한 좌심실 비대증의 위험성 감소와 같이 비만의 이차적인 증상 위험성을 낮추는데 유용하다.
본 발명의 펩티드 및 작용제는 만성 가성 장 폐쇄(Ogilvie's syndrome), 만성 가성 대장폐쇄, 크론씨병, 소화불량(기능성 또는 비궤양성 소화불량 포함), 십이지장-위 역류, 기능성 장 질환, 기능성 위장병, 기능성 속 쓰림, 위식도 역류성 질환(GERD), 위장 운동성 장애, 위부전마비(예, 특발성 위부전마비), 비대성 유문협착증(hypertrophic pyloric stenosis), 염증성 장 질환, 과민성 장 증후군(IBS), 수술후 장폐색, 및 궤양성 직장염을 포함하는, 위장 관련 장애의 치료 또는 예방에 있어서 단독으로 또는 병용요법으로 사용할 수 있다. 본 발명의 펩티드 및 작용제는 충격이나 외과적 개입으로 생기는 위장관 손상과 관련있는 위장 장애가 있는 환자나 또는 상기 위장 장애가 발생되기 쉬운 환자에 대해, 단독으로 또는 병용요법으로 사용할 수 있다. 본 발명의 펩티드 및 작용제는 위장관의 운동 저하증 또는 정지(stasis)과 관련된 특정 질환에 대한 위험성이 있거나 상기 질환이 있는 환자에 대해, 단독으로 또는 병용 요법으로 사용할 수 있다. 예컨대, 당뇨병성 신경병증, 거식증, 및 무위산증은 위장 운동 저하증에 의해 흔히 수반된다. 외과적 개입으로 인한 위장관 손상은, 예컨대 실질적인 위 정지를 발생시킬 수 있다. 본 발명 의 펩티드 및 작용제는 당뇨병 관련 위장병(예, 당뇨병성 위염)에 걸리기 쉬거나 걸린 환자에 대해, 단독으로 또는 병용요법으로 투여할 수 있다. 본 발명의 펩티드 및 작용제는 구역질, 구토, 속쓰림, 식후 불쾌감, 설사, 변비, 소화 불량 또는 관련 증상중 한가지 이상을 특징으로 하는 위장 질환의 예방 및/또는 치료를 위해, 단독으로 또는 병용요법으로 투여할 수 있다. 본 발명의 펩티드 및 작용제는 당뇨병, 거식증, 식욕 이상 항진, 무위산증, 식도이완불능증, 항문열상, 과민성 장 증후군, 가성 장 폐쇄, 경피증 및 위장 손상중 어느 하나와 관련 있는 위장 질환의 예방 및/또는 치료를 위해, 단독으로 또는 병용요법으로 투여할 수 있다.
본 발명의 펩티드 및 작용제는 변비(예, 치료제 복용으로 인한 변비; 신경병증성, 대사성 또는 내분비성 장애 관련 비만(자가 신경병증, 차가스 질환, 낭성 섬유증, 당뇨병, 히르시스프룽병, 갑상선 기능 항진증, 저칼슘혈증, 갑상선 기능 저하증, 다발성 경화증, 신경섬유종증, 파킨슨병 및 척수 손상을 포함); 수술후 변비(수술 후장 폐색); 위장병 관련 비만; 원발성 변비(기능성 변비 또는 통과 지연형 변비); 진통제 복용에 따른 변비(예, 오피오이드 유발성 변비); 그외 제제(예, 항고혈압제, 항경련제, 항우울제, 진경제 및 항정신병제)의 복용에 따른 변비; 거대결장(megacolon); 및 만성 변비)의 예방 및/또는 치료를 위해, 사용할 수 있다.
본 발명의 펩티드 및 작용제를 사용하여 장 운동성 저하, 소화 저하 및 위 공복 저하를 치료할 수 있다. 상기 펩티드 및 작용제는 IBS(더부룩함, 통증, 변지), GERD(식도로의 산 역류), 식도-위 역류, 기능성 소화불량 또는 위부전마비(구역질, 구토, 더부룩함, 지연성 위 공복) 및 본원에 기재된 그외 질환의 한가지 이상의 증상을 완화하는데 사용할 수 있다.
본 발명의 펩티드 및 작용제를 사용하여, 장 운동성을 증가시키고, 위장 무운동성(gastrointestinal immotility)과 하제 또는 변 완하 요법이 필요한 그외 증상을 예방 및/또는 치료할 수 있다. 위장 무운동성은 변비를 포함할 수 있으며, 또한 구강-맹장 통과 시간 지체, 불규칙한 탁세이션(irregular Taxation) 및 고형화(impaction)를 포함한 그외 관련 위장 운동 기능장애를 포함한다. 고형화는 흔히 만성 변비로 인해, 직장에 마르고 딱딱한 변이 다량 형성되는 현상이다. 이는 매우 딱딱하여 배출되기 어려울 수 있다. 변비나 위장 무운동성이 있는 환자는 하제 요법 및/또는 변 완화제 요법으로는 처리하기 어렵다.
본 발명의 펩티드 및 작용제는, 암, 전-암성 증식 또는 전이성 증식의 치료 또는 예방에 사용할 수 있다. 예컨대, 이는 결장직장/국소 국이된 결장직장 암, 대장용종(intestinal polyps), 위장관 암, 폐암, 표피 세포, 용종, 유방, 결장직장, ㅍ폐, 난소, 췌장, 전립선, 신장, 위, 방광, 간, 식도 및 고환의 암, 전-암성 증식 또는 전이성 증식, 암종(예, 기저세포, 호염기성 세포, Brown-Pearce, 유방내암, 알리히 종양(Ehrlich tumor), 크렙스(Krebs), 머켈 세포(Merkel cell), 소세포성 폐, 비-소세포성 폐, 연맥 세포(oat cell), 유두상, 세기관지, 편평상 세포, 전이 세포(transitional cell), (발커(Walker)), 백혈병(예, B-세포, T-세포, HTLV, 급성 또는 만성 림프구성, 비만 세포, 마이엘로이드), 조직구종(histiocytoma), 조직구증(histiocytosis), 홉킨스병, 비-홉킨스 림프종, 형질세포종(plasmacytoma), 세망내피증(reticuloendotheliosis), 선종(adenoma), 아데노- 암종(adeno-carcinoma), 선섬유종(fibradenoma), 선림프종(adenolymphoma), 법랑아세포종(ameloblastoma), 혈관각화종(angiokeratoma), 호산구 증가증을 동반한 혈관림프구 과형성(angiolymphoid hyperplasia with eosinophilia), 경화 혈관종(sclerosing angioma), 혈관암종(angiomatosis), 아푸도마(apudoma), 새종(branchioma), 악성 카시노이드 증후군(malignant carcinoid syndrome), 카시노이드 심장 질환(carcinoid heart disease), 암육종(carcinosarcoma), 백악종(cementoma), 담관종(cholangioma), 진주종(cholesteatoma), 연골육종(chondrosarcoma), 연골모세포종(chondroblastoma), 척색종(chordoma), 분리종(choristoma), 두개인두종(craniopharyngioma), 연골종(chrondroma), 기관지선종(cylindroma), 낭종암(cystadenocarcinoma), 낭선종(cystadenoma), 엽상 낭육종(Cystosarcoma phylloides), 디스게니노마(dysgenninoma), 뇌실막세포종(ependymoma), 유잉 육종(Ewing sarcoma), 섬유종(fibroma), 섬유육종(fibrosarcoma), 거대 세포 종양(giant cell tumor), 신경절성 신경종(ganglioneuroma), 교모세포종(glioblastoma), 사구맥관종(glomangioma), 과립막 세포종(granulosa cell tumor), 남녀성세포함유종양(gynandroblastoma), 과오종(hamartoma), 혈관내피종(hemangioendothelioma), 혈관종(hemangioma), 혈관주위세포종(hemangio-pericytoma), 혈관육종(hemangiosarcoma), 간암(hepatoma), 섬세포 종양(islet cell tumor), 카포시 육종(Kaposi sarcoma), 평활근종(leiomyoma), 평활근육종(leiomyosarcoma), 백혈육종(leukosarcoma), 레이디히 세포종(Leydig cell tumor), 지방종(lipoma), 지방육종(liposarcoma), 림프아우기오 마(lymphaugioma), 림프관근종(lymphangiomyoma), 림프관육종(lymphangiosarcoma), 속질모세포종(medulloblastoma), 수막종(meningioma), 간엽종(mesenchymoma), 중간콩팥종(mesonephroma), 중피세포암(mesothelioma), 근육모세포종(myoblastoma), 근종(myoma), 근육종(myosarcoma), 점액종(myxoma), 점액육종(myxosarcoma), 신경집종(neurilemmoma), 신경종(neuroma), 신경모세포종(neuroblastoma), 신경상피종(neuroepithelioma), 신경섬유종(neurofibroma), 신경섬유종증(neurofibromatosis), 치아종(odontoma), 골종(osteoma), 골육종(osteosarcoma), 유두종(papilloma), 부신경절종(paraganglioma), 부신경절증(paraganglionia), 논크로이나핀(nonchroinaffin), 솔방울샘종(pinealoma), 횡문근종(rhabdomyoma), 횡문근육종(rhabdomyosarcoma), 버팀 세포종(Sertoli cell tumor), 기형종(teratoma), 막세포종(theca cell tumor) 및 그외 세포가 이상 형성, 불멸화 또는 형질전환되는 질환의 예방 및 치료에 사용할 수 있다.
본 발명의 펩티드는 결장암에 선행되는 가족성 용종증(Familial Adenomatous Polyposis)(FAP)(상염색체 우성 증후군), 유전성 비용종증 결장직장 암(hereditary nonpolyposis colorectal cancer)(HNPCC) 및 유전성 상염색체 우성 증후군(inherited autosomal dominant syndrome)의 치료 또는 예방에 사용될 수 있다.
암, 전-암성 증식 또는 전이성 증식을 예방 및 치료하기 위해, 본 발명의 펩티드 및 작용제는 방사선, 화학치료제, cGMP-의존적 포스포디에스터라제 저해제 또는 선택적 사이클로옥시게나제-2 저해제와 병용 요법으로 사용할 수 있다. 다수의 선택적 사이클로옥시게나제-2 저해제가 미국 특허 20010024664, 미국 특허 5,380,738, 미국 특허 5,344,991, 미국 특허 5,393,790, 미국 특허 5,434,178, 미국 특허 5,474,995, 미국 특허 5,510,368, WO 02/062369, WO 96/06840, WO 96/03388, WO 96/03387, WO 96/19469, WO 96/25405, WO 95/15316, WO 94/15932, WO 94/27980, WO 95/00501, WO 94/13635, WO 94/20480, 및 WO 94/26731에 개시되어 있으며, 이들은 원용에 의해 본 명세서에 포함된다. [피라졸-1-일]벤젠설폰아미드 또한 사이클로옥시게나제-2의 저해제로 개시되어 있다.
본 발명의 펩티드 및 작용제는 염증의 치료 또는 예방에 사용할 수 있다. 따라서, 이들은 단독으로 또는 cGMP-의존적 포스포디에스터라제 저해제 또는 선택적 사이클로옥시게나제-2 저해제와 병용하여, 기관 염증, IBD(예, 크론씨 병, 궤양성 결장염), 천식, 신장염, 간염, 췌장염, 기관지염, 낭 섬유증, 허혈성 장 질환, 장 염증/알레르기, 복강신경 질환(coeliac disease), 직장염, 호산구성 위장염(Eosinophilic Gastroenteritis), 비만세포증 및 그외 염증성 질환의 치료에 사용할 수 있다. 본 발명의 펩티드 및 작용제는 단독으로 또는 병용요법으로 위장관 염증(위장 장애, 위장관 감염 또는 그외 질병 관련 염증)의 치료 또는 예방에 사용할 수 있다.
또한, 본 발명의 펩티드 및 작용제는 인슐린 관련 질환, 예컨대 II형 당뇨병, 고혈당증, 비만, 글루코스 또는 전해질 수송 교란과 관련된 질환, 세포에서의 인슐린 분비 장애와 관련된 질환 또는 내분비 질환을 치료하거나 또는 예방하는데 사용할 수 있다. 또한 이는 인슐린 저항성 치료 및 수술후 및 비-수술후 인슐린 반응 감소에 사용할 수 있다.
본 발명의 펩티드 및 작용제는 흡입, 환기 및 점액 분비 질환, 폐 고혈압, 혈관 및 기도의 만성적인 막힘 및 비가역적인 혈관 및 기관지 막힘을 포함한 폐 및 호흡기 질환을 예방하거나 치료하는데 사용할 수 있다. 본 발명의 제제는 기관지 경련 치료, 기관지 이완 유도, 만성적인 폐쇄성 폐 질환(정상적인 공기 흐름을 나타내는 만성 기관지염 포함)의 치료, 천식(기관지 천식, 내인성 천식, 외인성 천식, 만성 또는 난치성 천식(예, 말기 천식 및 기도과민반응), 먼지 유발성 천식, 알러겐 유발성 천식, 바이러스 유발성 천식, 한랭 유발성 천식(cold-induced asthma), 오염원 유발성 천식 및 운동 유발성 천식 포함)의 치료, 및 비염(급성-, 알레르기성, 헤트로픽(hatrophic) 비염 또는 만성 비염(예, 비염 지방(rhinitis caseosa), 비후성 비염(hypertrophic rhinitis), 화농성 비염(rhinitis purulenta), 건조성 비염(rhinitis sicca)), 약물 중독성 비염, 막성 비염(크루프성(croupous), 섬유소성(fibrinous) 및 가막성 비염 포함), 선병 비염(scrofulous rhinitis), 통년성 알레르기 비염(perennial allergic rhinitis), 계절성 비염(신경성 비염(헤이피버(hay fever)) 및 혈관운동성 비염(vasomotor rhinitis) 포함)의 치료에 사용할 수 있다. 또한, 본 발명의 펩티드는 안구 건조 질환 및 만성 부비강염(sinusitis)의 치료에 이용할 수도 있다. 본 발명의 펩티드는 폐렴으로부터 발생될 수 있는 급성 폐 수축, 외상성 손상, 흡인 또는 흡입 손상, 폐의 비장 색전증, 폐의 산증 염증(acidosis inflammation), 성인 호흡 곤란 증후군, 급성 폐부종, 급성 고산병, 심장 수술 후(post-cardiac surgery), 급성 폐 고혈압증, 신생아의 지속성 폐 고혈압증, 주산기 흡인 증후군(perinatal aspiration syndrome), 유 리질막병(hyaline membrane disease), 급성 폐동맥 혈색전증(acute pulmonary thromboembolism), 헤라핀-프로타민 반응증(herapin-protamine reactions), 패혈증, 천식 지속상태(status asthmaticus), 또는 저산소증(hypoxia)(의인성 저산소증(iatrogenic hypoxia) 포함), 및 그외 가역적 폐 수축을 특징으로 하는 질환의 예방 및/또는 치료에 사용할 수 있다. 또한, 이러한 폐 질환은 다양한 백혈구 서브클래스를 포함하는 폐의 비상주 세포 유형으로의 이동과 관련있는 염증을 포함한, 폐의 염증을 특징으로 한다. 또한, 수포성 질환, 기침, 염 관련 만성 기침, 의인성 유발 기침(iatrogenic induced cough), 기도 협색증(airway constriction), 비둘기 사육자 질환(pigeon fancier's disease), 호산구성 기관지염, 천식성 기관지염, 기도 폐쇄를 수반하는 만성 기관지염(만성 폐쇄성 기관지염), 호산구성 폐 질환, 폐기종, 농부 폐(farmer's lung), 알레르기성 눈병(알레르기성 결막염, 춘계 결막염(vernal conjunctivitis), 춘계 각결막염, 및 거대 유두 결막염(giant papillary conjunctivitis) 포함), 특발성 폐 섬유증, 낭성 섬유증, 미만성 범세기관기염(diffuse panbronchiolitis), 및 폐 염증 및/또는 점액 과다 배출을 특징으로 하는 그외 질환이 호흡기 질환에 포함된다. 그외 예방, 치료 또는 조절되는 것으로 포함되는 그외 생리적 현상으로는, 폐내 혈소판 활성화, 폐의 간질성 질환(ILD)와 같은 간질성 섬유증을 발생시키는 폐의 만성 염증 질환(예, 특발성 폐 섬유증 또는 류마토스 관절염 관련 ILD, 또는 그외 자가면역 질환), 만성 폐쇄성 폐 질환(COPD)(비가역적 COPD), 만성 부비강염, 섬유종 폐(fibroid lung), 과민성 폐 질환, 과민성 폐렴, 특발성 간질성 폐렴, 코막힘, 코의 용종(nasal polyposis) 및 중이염이 있다.
본 발명의 펩티드 및 작용제는 단독으로 또는 병용사용하여, 망막증, 신부전증, 당뇨병성 혈관병증 및 부종 형성을 예방 또는 치료할 수 있다.
본 발명의 펩티드 및 작용제는 단독으로 또는 병용사용하여, 신경성 질환, 예컨대, 두통, 편두통, 불안, 스트레스, 인지 장애(cognitive disorder), 뇌허혈증, 뇌 외상, 운동 장애, 공격성, 정신병, 발작, 공황 발작, 히스테리, 수면 장애, 우울증, 분열정동성 장애, 수면 무호흡증, 주의력 결핍 증후군, 기억 상실, 치매, Moncada and Higgs 1995 FASEB J. 9:1319-1330; Severina 1998 Biochemistry 63:794; Lee et al. 2000 PNAS 97: 10763-10768; Hobbs 1997 TIPS 18:484-491; Murad 1994 Adv. Pharmacol. 26:1-335; and Denninger et al. 1999 Biochim. Biophys. Acta 1411:334-350에 개시된 기억 및 학습 장애, 및 기면증을 예방 또는 치료할 수 있다. 또한, 이는 진정제로서 사용할 수 있다.
펩티드 및 검출가능하도록 표지된 펩티드는 크론씨 병, 결장염, 염증성 장 질환, 종양, 양성 위 종양과 같은 양성 종양, 선종(adenoma), 혈관종(angioma), 선종성(뇌각이 있고 꼭지가 없는) 용종(adenomatous polyps(pedunculated and sessile)), 악성, 카르시노이드 종양(carcinoid tumor), 내분비 세포 종양, 림프종, 선암종(adenocarcinoma), 앞창자종, 중간 창자종, 뒷창자종, 평활근종(leiomyoma), 세포성 평활근종(cellular leiomyoma), 평활근모세포종(leiomyoblastoma) 및 평활근육종(leiomyosarcoma)과 같은 위장 기질 종양(gastroinstestinal stromal tumor)(GIST)), 위장 자율신경종(gastrointestinal autonomic nerve tumor), 흡수장애 증후군(malabsorption syndromes), 복강 질환(celiac diseases), 게실증(diverticulosis), 멕켈씨 게실염(Meckel's diverticulurn), 결장 게실형성(colonic diverticula), 거대결장증(megacolon), 선천성 거대결장증(Hirschsprung's disease), 과민성 장 증후군, 장간막허혈증(mesenteric ischemia), 허혈성 장염(ischemic colitis), 직장결장암(colorectal cancer), 결장 폴립증(colonic polyposis), 용종 증후군(polyp syndrome), 장 선암종(intestinal adenocarcinoma), 리들 증후군(Liddle syndrome), 브로디 근병증(Brody myopathy), 영아 경련 및 무도무정위운동(choreoathetosis)을 포함한, 소장의 질환과 상태를 확인하고, 검사하고, 조작하고 또는 진단하기 위한 마커로서 사용할 수 있다.
본 발명의 펩티드 및 작용제는 GC-C 수용체를 가진 세포, 예컨대 낭종 섬유종 병변 및 장 관 내부의 특정 세포를 표적으로 하기 위해, 다른 분자(예, 진단성 분자 또는 치료 분자)와 접합시킬 수 있다. 따라서, 상기 펩티드는 소장에 방사성 모이어티 또는 치료학적 모이어티를 표적화하는데 사용하여, 결장직장/전이성 또는 국소 결장직장 암의 영상화, 진단, 또는 치료를 보조하고, 장관에 p53 종양 억제 유전자의 정상 카피를 전달할 수 있다. 본 발명의 펩티드 및 작용제를 사용하여 세포 표면상의 GC-C 분자의 수를 증가시킬 수 있다. 일부 예들에서, 세포는 전이된 결장직장 암 세포이다. 일 예에서, 본 발명의 펩티드 또는 작용제는 제2의 제제와 치료학적으로 접합된다. 특정 예에서, 상기 제2의 제제는 방사능이 있거나 또는 방사안정성을 가질 수 있다. 특정 예에서, 상기 제2의 제제는 세포 사멸을 초래하는 화합물, 세포 분열을 저해하는 화합물, 세포 분화를 유도하는 화합물, 화학적 치료제, 독소 및 방사능감작성 제제로 이루어진 군으로부터 선택될 수 있다. 특정 예에서, 상기 제2의 제제는 메토트렉세이트, 독소루비신, 다우노루비신(daunorubicin), 사이토시나라비노시드(cytosinarabinoside), 에토포시드(etoposide), 5-4 플루오로우라실, 멜팔란(melphalan), 클로람부실, 시스플라틴, 빈데신(vindesine), 미토마이신(mitomycin), 블레오마이신(bleomycin), 퓨로티오닌(purothionin), 마크로모마이신(macromomycin), 1,4-벤조퀴논 유도체, 트레니몬(trenimon), 리신(ricin), 리신 A 체인, 슈도모나스 외독소(Pseudomonas exotoxin), 디프테리아 독소, 클로스트리듐 퍼프린겐스 포스포리파제 C(Clostridium perfringens phospholipase C), 소 췌장의 리보뉴클레아제, PAP(pokeweed antiviral protein), 아브린(abrin), 아브린 A 체인, 코브라 독 인자, 겔로닌(gelonin), 사포린(saporin), 모데신(modeccin), 비스쿠민(viscumin), 볼켄신(volkensin), 니트로이미다졸(nitroimidazole), 메트로니다졸(metronidazole) 및 미소니다졸(misonidazole)로 이루어진 군으로부터 선택될 수 있다.
본 발명의 펩티드 및 작용제는 단독으로 또는 병용요법으로 사용하여, 내이 질환, 예컨대 메니에르병(Meniere's disease)(현기증, 청력 감퇴, 이명, 귀내 불쾌감과 같은 질환의 증상을 포함), 상륙 증후군(Mal de d barquement syndrome), 외이염, 중이염, 이루(otorrhea), 급성 유양 돌기염(acute mastoiditis), 이경화증(otosclerosis), 귀의 통증, 귀 출혈, 귀 염증, 레르모예즈 증후군(Lermoyez's syndrome), 전정신경염(vestibular neuronitis), 양성 발작성 두위변환성 현훈(benign paroxysmal positional vertigo)(BPPV), 귀의 대상 포진(herpes zoster oticus), 람세이 헌트 증후군(Ramsay Hunt's syndrome), 헤르페스, 미로염(labyrinthitis), 화농성 미로염(purulent labyrinthitis), 외림프 누공(perilymph fistulas), 노인성 난청(presbycusis), 이독성(ototoxicity)(약물 유발성 이동성 포함), 청신경종(neuromas)(청각종양(acoustic neuromas) 포함), 항공 중이염(aerotitis media), 감염성 고막염(infectious myringitis), 수포성 고막염(bullous myringitis), 편평세포 종양, 기저 세포 종양, 전-암성 귀 증상(pre-cancerous otic condition), 안와 부신경절종(nonchromaffin paragangliomas), 화학감수체종(chemodectomas), 경정맥구 사구종(glomus jugulare tumor), 실사구종(glomus tympanicum tumor), 연골막염(perichondritis), 귀 습진양 피부염(aural eczematoid dermatitis), 악성 외이도염(malignant external otitis), 연골막하 혈종(subperichondrial hematoma), 귀지샘종(ceruminoma), 이구전색(impacted cerumen), 지루성 낭종(sebaceous cysts), 골종(osteomas), 켈로이드(keloid), 귀앓이(otalgia), 이명, 고막 감염증(tympanic membrane infection), 고실염(tympanitis), 귀 종기(otic furuncle), 추체염(petrositis), 전음성 및 감각신경성 난청(conductive and sensorineural hearing loss), 경막외 농양(epidural abscess), 횡정맥동혈전증(lateral sinus thrombosis), 경막하축농(subdural empyema), 귀 수두증(otitic hydrocephalus), 댄디 증후군(Dandy's syndrome), 수포성 고막염, 광범성 외이도염(diffuse external otitis), 이물질(foreign bodies), 폐쇄각화증(keratosis obturans), 귀 종양(otic neoplasm), 귀진균증(otomycosis), 외상, 급성 기압성 중이염(acute barotitis media), 급성 귀인두관의 폐색(acute eustachian tube obstruction), 수술후 귀통증, 진주종(cholesteatoma), 귀 수술 관련 감염증 및 상기 임의 질환 관련 합병증을 예방 및/또는 치료할 수 있다. 본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 내이, 신경염(바이러스성 신경염 포함), 신경절염, 슬상(geniculate)에서의 유동액 항상성을 유지시킬 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여, 유액 및 소듐 저류(fluid and sodium retention)와 관련된 질환, 예컨대 신장, 장 및 비뇨생식계에서의 전해질-물/전해질 수송 시스템 질환, 울혈성 심부전증, 고혈압, 저혈압, 염 의존형 고혈압, 간 부종 및 간 경변증을 예방 및/또는 치료할 수 있다. 또한 이를 사용하여 이뇨를 원활하게 하거나 장액을 조절할 수 있다. 또한, 본 발명의 펩티드 및 작용제를 사용하여 신장내 상피 세포의 비정상적인 증상이 이루어지는 질환(예, 신장암의 경우)을 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 신장 질환을 예방/또는 치료할 수 있다. "신장 질환"은 신부전(renal failure)(급성 신부전 포함), 신부전증(renal insufficiency), 신부종(nephrotic edema), 사구체신염(glomerulonephritis), 신우신염(pyelonephritis), 신장 장애(kidney failure), 만성 신부전, 신염(nephritis), 신증(nephrosis), 고질소혈증(azotemia), 요독증, 면역성 신장 질환(immune renal disease), 급성 신염 증후군, 급속 진행성 신염 증 후군, 신 증후군(nephrotic syndrome), 버거스 병(Berger's Disease), 만성 신염 증후군(chronic nephritic syndrome), 만성 단백뇨 증후군(chronic proteinuric syndrome), 세뇨관 간질성 질환(tubulointerstitial disease), 신독성 질환(nephrotoxic disorder), 신경색(renal infarction), 신혈관색전증(atheroembolic renal disease), 신 피질 괴사(renal cortical necrosis), 악성 신장혈관경화증(malignant nephroangiosclerosis), 신정맥 혈전증(renal vein thrombosis), 신 세뇨관성 산증(renal tubular acidosis), 신 당뇨(renal glucosuria), 신 원발성 요붕증(nephrogenic diabetes insipidus), 바터 증후군(Bartter's Syndrome), 리들 증후군(Liddle's Syndrome), 다낭성 신장 질환(polycystic kidney disease), 수질 낭성 신질환(medullary cystic disease), 수질 해면신(medullary sponge kidney), 유전성 신장염(hereditary nephritis), 손발톱 슬개골 증후군(nail-patella syndrome), 신장계 관련 모든 질환 또는 장애와, 신(renal) 또는 신장(kidney) 질환 및 관련 장애를 나타내는 증상 또는 관련 증상을 포함한다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 다낭성 신장 질환을 예방/또는 치료할 수 있다. 다낭성 신장 질환 "PKD"("polycystic renal disease")은 매우 커진 신장에 다수개의 낭종이 분포된 것을 특징으로 하는 질환의 일종이다. 발생된 낭종은 신장의 기능을 해치고, 궁극적으로 신 부전을 초래할 수 있다. "PKD"는 특히 원인 불문하고 모든 발생 단계에서의 상염색체 우성 다낭성 신장 질환(autosomal dominant polycystic kidney disease (ADPKD))와 상염색체 열 성 다낭성 신장 질환(autosomal recessive polycystic kidney disease (ARPKD))을 포함한다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 바이카보네이트 배룰과 관련된 질병, 예컨대 낭성 섬유증을 예방/또는 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 담즙 배출 관련 질환을 예방/또는 치료할 수 있다. 또한, 이는 사용하여 담낭에서 클로라이드 및 담즙액 배출을 용이하게 하거나 통제할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여, 간 세포 재생 관련 질환을 예방/또는 치료할 수 있다. 이는 상기 펩티드 및 작용제를 간 이식 수여체와 약물 또는 알코올로 인한 간 손상 환자에게 투여하는 것을 포함할 수 있다. 또한, 상기 펩티드 및 작용제는 바이러스 매개성 간염과 같은 간 손상을 치료하는데 유용할 수 있다. 본 발명의 펩티드 및 작용제를 단독 또는 병용사용하여, 간농양(liver abscess), 간암(원발성 또는 전이성), 경변(알콜 소비로 인한 경변 또는 원발성 담즙성 경변), 아메바성 간농양(amebic liver abscess), 자가면역성 간염, 담관형성 부전증(biliary atresia), 파종성 콕시디오이데스 진균증(coccidioidomycosis disseminated), δ제제(간염 δ), 혈색소증, 간염 a, 간염 b, 간염 c, 또는 바이러스성, 대사성 또는 독성 병인으로 인한 그외 모든 급성, 아급성, 전격성 또는 만성 간염, 간세포성 암종, 화농성 간농약(pyogenic liver abscess), 라이에 증후군(Reye's syndrome), 경화성 담도염(sclerosing cholangitis), 윌슨 병(Wilson's disease), 약물 유발성 간독성 또는 전격성 또는 급성 간 부전증을 예방 및/또는 치료할 수 있다. 본 발명의 펩티드 및 작용제는 간절제술 수술 이후에 간 재생을 촉진하는데 사용할 수도 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여, 심근경색, 이완 기능 장애(diastolic dysfunction), 협심증, 안정성, 불안정성 및 이형(프린즈메탈) 협심증, 죽상동맥경화, 혈전증, 내피세포 기능 장애(endothelial dysfunction), 심장 부종, 발작, 혈관 개통 저하 증상, 예컨대 관상동맥 확장술 이후(postpercutaneous transluminal coronary angioplasty)(post-PTCA) 및 말초 혈관 질환을 예방 및/또는 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 녹내장을 예방 및/또는 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 면역결핍증을 예방 및/또는 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 요로폐색(bladder outlet obstruction) 및 실금을 예방 및/또는 치료할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 남성(예, 발기 불능) 또는 여성의 성 기능 장애, 조기 분만 및 월경 곤란증을 예방 및/또는 치료할 수 있다. 특정 예에서, 이는 포스포디에스테라제 저해제와 병용 사용할 수 있다.
본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 골감소성 질병(골 소실 질환)을 예방 및/또는 치료할 수 있다. "골 소실 질환"은 골 소실 저해 및/또는 골 형성 촉진이 바람직한 질병 및 증상을 포함한다. 이러한 질병 및 증상들로는, 골다공증, 골수염, 파제트 병(Paget's disease)(변형성 골염(osteitis deformans)), 치근막염(periodontitis), 혈중 고칼슘증(hypercalcemia), 골괴사(osteonecrosis), 골육종(osteosarcoma), 골용해성 전이(osteolyic metastase), 가족성 팽창성 골용해(familial expansile osteolysis), 인공삽입물의 해리(prosthetic loosening), 인공삽입물 주위의 골용해(periprostetic osteolysis), 골소실이 동반된 류마토스 관절염(bone loss attendant rheumatoid arthritis) 및 쇄골두개형성부전증(cleidocranial dysplasia)(CCD)이 있다. 골다공증은 일차성 골다공증(primary osteoporosis), 내분비 골다공증(endocrine osteoporosis)(갑상선 기능 항진증, 부갑상선 기능 항진증, 쿠싱 증후군(Cushing's syndrome) 및 말단비대증(acromegaly), 유전성 및 선천성 골다공증(골형성 부전증(osteogenesis imperfecta), 호모시스틴뇨증(homocystinuria), 메케스 증후군(Menkes' syndrome) 및 릴-데이 증후군(Rile-Day syndrome)), 말단골수염(extremitiesosteomyelitis)의 고정화로 인한 골다공증 및 골 소실을 유발하는 골의 감염성 상처로 인한 골다공증이 있다. 본 발명의 펩티드 및 작용제를 단독 또는 병용요법으로 사용하여 골 재생을 촉진시킬 수 있다. 두개악안면외과(Cranio-Maxillofacial Surgery)에서의 골 결함의 재건, 또는 골에 임플란트 삽입, 예컨대 치아 임플란트, 골 지지성 임플란트 또는 인공삽입물 삽입 이후에 골 재생을 실시할 수 있다. 또한, 골절 이후에 골 재생을 실시할 수 있다.
본 발명의 ST 펩티드에 대해 상동성을 가지는 펩티드는 면역원으로서 사용하 여, 여행자 설사와 관련된 질환의 한가지 이상의 증상을 치료 및/또는 예방할 수 있다. 미국 특허 20040146534, US4220584, US4285391, US5182109, US4603049, US4545931, US4886663, 및 WO 08402700에 개시된 방법은 본 발명의 펩티드를 포함하는 면역원 제조에 유사하게 사용할 수 있다.
SEQUENCE LISTING <110> Microbia, Inc. <120> METHODS AND COMPOSITIONS FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS <130> 14184-057WO1 <140> PCT/US2005/007752 <141> 2005-03-08 <150> US 10/899,806 <151> 2004-07-24 <150> US 10/845,895 <151> 2004-05-14 <150> US 10/796,719 <151> 2004-03-09 <150> US 11/054,071 <151> 2005-02-08 <160> 2084 <170> FastSEQ for Windows Version 4.0 <210> 1 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> 1, 2, 3, 4, 5 <223> Xaa = Xaa1 = Asn, Xaa2 = Ser, Xaa3 = Ser, Xaa4 = Asn, Xaa5 = Tyr; or is missing <220> <221> VARIANT <222> 8, 9, 12, 13, 14, 17, 19, 20, 21 <223> Xaa = any amino acid <400> 1 Xaa Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Cys Cys Xaa Xaa Xaa Cys Xaa 1 5 10 15 Xaa Cys Xaa Xaa Xaa 20 <210> 2 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> 9 <223> Xaa = any amino acid; or Xaa = any amino acid other than Leu; or Xaa = Phe, Trp, and Tyr; or selected from from any other natural or non-natural aromatic amino acid; or Xaa = Tyr <220> <221> VARIANT <222> 1, 2, 3, 4, 5 <223> Xaa1 = Asn, Xaa2 = Ser, Xaa3 = Ser, Xaa4 = Asn, Xaa5 = Tyr; or Xaa1-Xaa5 is missing; or Xaa1-Xaa4 is missing; or Xaa1 -Xaa3 is missing; or Xaa1 and Xaa2 is missing; or Xaa1 is missing <220> <221> VARIANT <222> 19, 20, 21 <223> Xaa 20 = Asp, Xaa21 = Phe; or missing; or Xaa20 = Asn or Glu and Xaa21 is missing; or X19-Xaa21 is missing <400> 2 Xaa Xaa Xaa Xaa Xaa Cys Cys Glu Xaa Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Xaa Xaa 20 <210> 3 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 3 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 4 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 4 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 5 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 5 Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 6 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 6 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 7 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 7 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp 1 5 10 15 Gly Cys Tyr <210> 8 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 8 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr 1 5 10 <210> 9 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 9 Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 10 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 10 Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr 1 5 10 15 <210> 11 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 11 Asn Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 12 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 12 Asn Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 13 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 13 Asn Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 14 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 14 Asn Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 15 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 15 Asn Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 16 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 16 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 17 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 17 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 18 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 18 Asn Ser Ser Asn Tyr Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 19 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 19 Asn Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 20 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 20 Asn Ser Ser Asn Tyr Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 21 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 21 Asn Ser Ser Asn Tyr Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 22 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 22 Asn Ser Ser Asn Tyr Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr Asp Phe 20 <210> 23 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 23 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 24 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 24 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr Asp Phe 1 5 10 15 <210> 25 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 25 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 26 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 26 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 27 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 27 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 28 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 28 Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 29 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 29 Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp Phe 1 5 10 15 <210> 30 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 30 Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 31 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 31 Asn Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Trp Gly Cys Tyr Asp 1 5 10 15 Phe <210> 32 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 32 Asn Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 33 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 33 Asn Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 34 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 34 Asn Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 35 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 35 Asn Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 36 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 36 Asn Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr Asp 1 5 10 15 Phe <210> 37 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 37 Gln Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 38 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 38 Asn Thr Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 39 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 39 Asn Leu Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 40 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 40 Asn Ile Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 41 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 41 Asn Ser Ser Gln Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 42 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 42 Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 43 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 43 Gln Ser Ser Gln Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 44 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 44 Ser Ser Gln Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 45 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 45 Asn Ser Ser Asn Tyr Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 46 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 46 Asn Ser Ser Asn Tyr Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 47 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 47 Asn Ser Ser Asn Tyr Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 48 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 48 Asn Ser Ser Asn Tyr Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 49 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 49 Asn Ser Ser Asn Tyr Cys Cys Glu Cys Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 50 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 50 Asn Ser Ser Asn Tyr Cys Cys Glu Gln Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 51 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 51 Asn Ser Ser Asn Tyr Cys Cys Glu Glu Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 52 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 52 Asn Ser Ser Asn Tyr Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 53 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 53 Asn Ser Ser Asn Tyr Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 54 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 54 Asn Ser Ser Asn Tyr Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 55 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 55 Asn Ser Ser Asn Tyr Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 56 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 56 Asn Ser Ser Asn Tyr Cys Cys Glu Met Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 57 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 57 Asn Ser Ser Asn Tyr Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 58 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 58 Asn Ser Ser Asn Tyr Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 59 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 59 Asn Ser Ser Asn Tyr Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 60 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 60 Asn Ser Ser Asn Tyr Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 61 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 61 Asn Ser Ser Asn Tyr Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 62 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 62 Asn Ser Ser Asn Tyr Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 63 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 63 Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 64 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 64 Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 65 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 65 Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 66 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 66 Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 67 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 67 Cys Cys Glu Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 68 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 68 Cys Cys Glu Gln Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 69 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 69 Cys Cys Glu Glu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 70 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 70 Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 71 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 71 Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 72 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 72 Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 73 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 73 Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 74 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 74 Cys Cys Glu Met Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 75 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 75 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 76 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 76 Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 77 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 77 Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 78 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 78 Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 79 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 79 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 80 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 80 Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 81 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 81 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 82 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 82 Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 83 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 83 Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 84 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 84 Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 85 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 85 Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 86 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 86 Cys Cys Glu Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 87 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 87 Cys Cys Glu Gln Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 88 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 88 Cys Cys Glu Glu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 89 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 89 Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 90 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 90 Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 91 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 91 Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 92 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 92 Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 93 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 93 Cys Cys Glu Met Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 94 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 94 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 95 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 95 Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 96 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 96 Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 97 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 97 Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 98 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 98 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 99 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 99 Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 100 <211> 19 <212> PRT <213> Escherichia coli <400> 100 Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr 1 5 10 15 Gly Cys Tyr <210> 101 <211> 18 <212> PRT <213> Escherichia coli <400> 101 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Ala Gly 1 5 10 15 Cys Tyr <210> 102 <211> 18 <212> PRT <213> Escherichia coli <400> 102 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Tyr Pro Ala Cys Ala Gly 1 5 10 15 Cys Asn <210> 103 <211> 18 <212> PRT <213> Citrobacter freundii <400> 103 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Ala Gly 1 5 10 15 Cys Tyr <210> 104 <211> 30 <212> PRT <213> Yersinia enterocolitica <400> 104 Gln Ala Cys Asp Pro Pro Ser Pro Pro Ala Glu Val Ser Ser Asp Trp 1 5 10 15 Asp Cys Cys Asp Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 20 25 30 <210> 105 <211> 30 <212> PRT <213> Yersinia enterocolitica <400> 105 Gln Ala Cys Asp Pro Pro Leu Pro Pro Ala Glu Val Ser Ser Asp Trp 1 5 10 15 Asp Cys Cys Asp Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 20 25 30 <210> 106 <211> 30 <212> PRT <213> Yersinia enterocolitica <400> 106 Lys Ala Cys Asp Thr Gln Thr Pro Ser Pro Ser Glu Glu Asn Asp Asp 1 5 10 15 Trp Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 20 25 30 <210> 107 <211> 53 <212> PRT <213> Yersinia enterocolitica <400> 107 Gln Glu Thr Ala Ser Gly Gln Val Gly Asp Val Ser Ser Ser Thr Ile 1 5 10 15 Ala Thr Glu Val Ser Glu Ala Glu Cys Gly Thr Gln Ser Ala Thr Thr 20 25 30 Gln Gly Glu Asn Asp Trp Asp Trp Cys Cys Glu Leu Cys Cys Asn Pro 35 40 45 Ala Cys Phe Gly Cys 50 <210> 108 <211> 16 <212> PRT <213> Yersinia kristensenii <400> 108 Ser Asp Trp Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 1 5 10 15 <210> 109 <211> 17 <212> PRT <213> Vibrio cholerae <400> 109 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu 1 5 10 15 Asn <210> 110 <211> 17 <212> PRT <213> Vibrio mimicus <400> 110 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu 1 5 10 15 Asn <210> 111 <211> 18 <212> PRT <213> Escherichia coli <400> 111 Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Ala Pro 1 5 10 15 Cys Tyr <210> 112 <211> 13 <212> PRT <213> Vibrio cholerae <400> 112 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe 1 5 10 <210> 113 <211> 14 <212> PRT <213> Vibrio cholerae <400> 113 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly 1 5 10 <210> 114 <211> 17 <212> PRT <213> Vibrio mimicus <400> 114 Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu 1 5 10 15 Asn <210> 115 <211> 17 <212> PRT <213> Vibrio mimicus <400> 115 Ile Asp Arg Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe Gly Cys Leu 1 5 10 15 Asn <210> 116 <211> 16 <212> PRT <213> Yersinia enterocolitica <400> 116 Asp Trp Asp Cys Cys Asp Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 1 5 10 15 <210> 117 <211> 16 <212> PRT <213> Yersinia enterocolitica <400> 117 Asp Trp Asp Cys Cys Asp Val Cys Cys Asn Pro Ala Cys Ala Gly Cys 1 5 10 15 <210> 118 <211> 17 <212> PRT <213> Yersinia enterocolitica <400> 118 Asn Asp Asp Trp Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Ala Gly 1 5 10 15 Cys <210> 119 <211> 16 <212> PRT <213> Yersinia enterocolitica <400> 119 Trp Asp Trp Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Phe Gly Cys 1 5 10 15 <210> 120 <211> 30 <212> PRT <213> Yersinia enterocolitica <400> 120 Gln Ala Cys Asp Pro Pro Ser Pro Pro Ala Glu Val Ser Ser Asp Trp 1 5 10 15 Asp Cys Cys Asp Val Cys Cys Asp Pro Ala Cys Ala Gly Cys 20 25 30 <210> 121 <211> 72 <212> PRT <213> Escherichia coli <400> 121 Met Lys Lys Leu Met Leu Ala Ile Phe Ile Ser Val Leu Ser Phe Pro 1 5 10 15 Ser Phe Ser Gln Ser Thr Glu Ser Leu Asp Ser Ser Lys Glu Lys Ile 20 25 30 Thr Leu Glu Thr Lys Lys Cys Asp Val Val Lys Asn Asn Ser Glu Lys 35 40 45 Lys Ser Glu Asn Met Asn Asn Thr Phe Tyr Cys Cys Glu Leu Cys Cys 50 55 60 Asn Pro Ala Cys Ala Gly Cys Tyr 65 70 <210> 122 <211> 72 <212> PRT <213> Escherichia coli <400> 122 Met Lys Lys Ser Ile Leu Phe Ile Phe Leu Ser Val Leu Ser Phe Ser 1 5 10 15 Pro Phe Ala Gln Asp Ala Lys Pro Val Glu Ser Ser Lys Glu Lys Ile 20 25 30 Thr Leu Glu Ser Lys Lys Cys Asn Ile Ala Lys Lys Ser Asn Lys Ser 35 40 45 Gly Pro Glu Ser Met Asn Ser Ser Asn Tyr Cys Cys Glu Leu Cys Cys 50 55 60 Asn Pro Ala Cys Thr Gly Cys Tyr 65 70 <210> 123 <211> 71 <212> PRT <213> Yersinia enterocolitica <400> 123 Met Lys Lys Ile Val Phe Val Leu Val Leu Met Leu Ser Ser Phe Gly 1 5 10 15 Ala Phe Gly Gln Glu Thr Val Ser Gly Gln Phe Ser Asp Ala Leu Ser 20 25 30 Thr Pro Ile Thr Ala Glu Val Tyr Lys Gln Ala Cys Asp Pro Pro Leu 35 40 45 Pro Pro Ala Glu Val Ser Ser Asp Trp Asp Cys Cys Asp Val Cys Cys 50 55 60 Asn Pro Ala Cys Ala Gly Cys 65 70 <210> 124 <211> 53 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 124 Met Lys Lys Ser Ile Leu Phe Ile Phe Leu Ser Val Leu Ser Phe Ser 1 5 10 15 Pro Phe Ala Gln Asp Ala Lys Pro Ala Gly Ser Ser Lys Glu Lys Ile 20 25 30 Thr Leu Glu Ser Lys Lys Cys Asn Ile Val Lys Lys Ser Asn Lys Ser 35 40 45 Gly Pro Glu Ser Met 50 <210> 125 <211> 53 <212> PRT <213> Escherichia coli <400> 125 Met Lys Lys Ser Ile Leu Phe Ile Phe Leu Ser Val Leu Ser Phe Ser 1 5 10 15 Pro Phe Ala Gln Asp Ala Lys Pro Ala Gly Ser Ser Lys Glu Lys Ile 20 25 30 Thr Leu Glu Ser Lys Lys Cys Asn Ile Val Lys Lys Asn Asn Glu Ser 35 40 45 Ser Pro Glu Ser Met 50 <210> 126 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 126 Asn Ser Ser Asn Tyr 1 5 <210> 127 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 127 Lys Lys Lys Lys Lys Lys 1 5 <210> 128 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 128 Asp Lys Lys Lys Lys Lys Lys 1 5 <210> 129 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> 1, 2, 3, 4, 5 <223> Xaa1 = Asn, Xaa2 = Ser, Xaa3 = Ser, Xaa4 = Asn, Xaa5 = Tyr or missing; or Xaa1- Xaa4 is missing and Xaa5 = Asn <220> <221> VARIANT <222> 8 <223> Xaa = Glu or Asp <220> <221> VARIANT <222> 9 <223> Xaa = Leu, Ile, Val, Trp, Tyr or Phe <220> <221> VARIANT <222> 16 <223> Xaa = Thr, Ala, or Trp <220> <221> VARIANT <222> 19 <223> Xaa = Trp, Tyr, Or Leu or is missing <220> <221> VARIANT <222> 20, 21 <223> Xaa = Asp, Phe <400> 129 Xaa Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa 1 5 10 15 Gly Cys Xaa Xaa Xaa <210> 130 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 130 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 131 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 131 Cys Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 132 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 132 Cys Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 133 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 133 Cys Cys Cys Cys Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 134 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 134 Cys Cys Cys Cys Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 135 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 135 Cys Cys Cys Cys Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 136 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 136 Cys Cys Cys Cys Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 137 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 137 Cys Cys Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 138 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 138 Cys Cys Cys Cys Asn Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 139 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 139 Cys Cys Cys Cys Asn Cys Thr Gly Cys Tyr 1 5 10 <210> 140 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 140 Cys Cys Cys Cys Asn Ala Cys Gly Cys Tyr 1 5 10 <210> 141 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 141 Cys Cys Cys Cys Asn Ala Cys Thr Cys Tyr 1 5 10 <210> 142 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 142 Cys Cys Cys Cys Asn Ala Cys Thr Gly Cys 1 5 10 <210> 143 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 143 Cys Cys Cys Cys Asn Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 144 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 144 Cys Cys Cys Cys Asn Pro Cys Gly Cys Tyr 1 5 10 <210> 145 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 145 Cys Cys Cys Cys Asn Pro Cys Thr Cys Tyr 1 5 10 <210> 146 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 146 Cys Cys Cys Cys Asn Pro Cys Thr Gly Cys 1 5 10 <210> 147 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 147 Cys Cys Cys Cys Asn Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 148 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 148 Cys Cys Cys Cys Asn Pro Ala Cys Cys Tyr 1 5 10 <210> 149 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 149 Cys Cys Cys Cys Asn Pro Ala Cys Gly Cys 1 5 10 <210> 150 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 150 Cys Cys Cys Cys Asn Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 151 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 151 Cys Cys Cys Cys Asn Pro Ala Cys Thr Cys 1 5 10 <210> 152 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 152 Cys Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 153 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 153 Cys Cys Tyr Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 154 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 154 Cys Cys Tyr Cys Cys Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 155 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 155 Cys Cys Tyr Cys Cys Cys Thr Gly Cys Tyr 1 5 10 <210> 156 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 156 Cys Cys Tyr Cys Cys Ala Cys Gly Cys Tyr 1 5 10 <210> 157 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 157 Cys Cys Tyr Cys Cys Ala Cys Thr Cys Tyr 1 5 10 <210> 158 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 158 Cys Cys Tyr Cys Cys Ala Cys Thr Gly Cys 1 5 10 <210> 159 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 159 Cys Cys Tyr Cys Cys Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 160 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 160 Cys Cys Tyr Cys Cys Pro Cys Gly Cys Tyr 1 5 10 <210> 161 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 161 Cys Cys Tyr Cys Cys Pro Cys Thr Cys Tyr 1 5 10 <210> 162 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 162 Cys Cys Tyr Cys Cys Pro Cys Thr Gly Cys 1 5 10 <210> 163 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 163 Cys Cys Tyr Cys Cys Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 164 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 164 Cys Cys Tyr Cys Cys Pro Ala Cys Cys Tyr 1 5 10 <210> 165 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 165 Cys Cys Tyr Cys Cys Pro Ala Cys Gly Cys 1 5 10 <210> 166 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 166 Cys Cys Tyr Cys Cys Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 167 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 167 Cys Cys Tyr Cys Cys Pro Ala Cys Thr Cys 1 5 10 <210> 168 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 168 Cys Cys Tyr Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 169 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 169 Cys Cys Tyr Cys Cys Asn Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 170 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 170 Cys Cys Tyr Cys Cys Asn Cys Thr Gly Cys Tyr 1 5 10 <210> 171 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 171 Cys Cys Tyr Cys Cys Asn Cys Gly Cys Tyr 1 5 10 <210> 172 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 172 Cys Cys Tyr Cys Cys Asn Cys Thr Cys Tyr 1 5 10 <210> 173 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 173 Cys Cys Tyr Cys Cys Asn Cys Thr Gly Cys 1 5 10 <210> 174 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 174 Cys Cys Tyr Cys Cys Asn Ala Cys Gly Cys Tyr 1 5 10 <210> 175 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 175 Cys Cys Tyr Cys Cys Asn Ala Cys Cys Tyr 1 5 10 <210> 176 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 176 Cys Cys Tyr Cys Cys Asn Ala Cys Gly Cys 1 5 10 <210> 177 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 177 Cys Cys Tyr Cys Cys Asn Ala Cys Thr Cys Tyr 1 5 10 <210> 178 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 178 Cys Cys Tyr Cys Cys Asn Ala Cys Thr Cys 1 5 10 <210> 179 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 179 Cys Cys Tyr Cys Cys Asn Ala Cys Thr Gly Cys 1 5 10 <210> 180 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 180 Cys Cys Tyr Cys Cys Asn Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 181 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 181 Cys Cys Tyr Cys Cys Asn Pro Cys Gly Cys Tyr 1 5 10 <210> 182 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 182 Cys Cys Tyr Cys Cys Asn Pro Cys Cys Tyr 1 5 10 <210> 183 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 183 Cys Cys Tyr Cys Cys Asn Pro Cys Gly Cys 1 5 10 <210> 184 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 184 Cys Cys Tyr Cys Cys Asn Pro Cys Thr Cys Tyr 1 5 10 <210> 185 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 185 Cys Cys Tyr Cys Cys Asn Pro Cys Thr Cys 1 5 10 <210> 186 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 186 Cys Cys Tyr Cys Cys Asn Pro Cys Thr Gly Cys 1 5 10 <210> 187 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 187 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 188 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 188 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Cys Tyr 1 5 10 <210> 189 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 189 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Cys 1 5 10 <210> 190 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 190 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Gly Cys 1 5 10 <210> 191 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 191 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 192 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 192 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Cys 1 5 10 <210> 193 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 193 Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 194 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 194 Cys Cys Glu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 195 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 195 Cys Cys Glu Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 196 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 196 Cys Cys Glu Cys Cys Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 197 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 197 Cys Cys Glu Cys Cys Cys Thr Gly Cys Tyr 1 5 10 <210> 198 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 198 Cys Cys Glu Cys Cys Ala Cys Gly Cys Tyr 1 5 10 <210> 199 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 199 Cys Cys Glu Cys Cys Ala Cys Thr Cys Tyr 1 5 10 <210> 200 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 200 Cys Cys Glu Cys Cys Ala Cys Thr Gly Cys 1 5 10 <210> 201 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 201 Cys Cys Glu Cys Cys Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 202 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 202 Cys Cys Glu Cys Cys Pro Cys Gly Cys Tyr 1 5 10 <210> 203 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 203 Cys Cys Glu Cys Cys Pro Cys Thr Cys Tyr 1 5 10 <210> 204 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 204 Cys Cys Glu Cys Cys Pro Cys Thr Gly Cys 1 5 10 <210> 205 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 205 Cys Cys Glu Cys Cys Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 206 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 206 Cys Cys Glu Cys Cys Pro Ala Cys Cys Tyr 1 5 10 <210> 207 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 207 Cys Cys Glu Cys Cys Pro Ala Cys Gly Cys 1 5 10 <210> 208 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 208 Cys Cys Glu Cys Cys Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 209 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 209 Cys Cys Glu Cys Cys Pro Ala Cys Thr Cys 1 5 10 <210> 210 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 210 Cys Cys Glu Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 211 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 211 Cys Cys Glu Cys Cys Asn Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 212 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 212 Cys Cys Glu Cys Cys Asn Cys Thr Gly Cys Tyr 1 5 10 <210> 213 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 213 Cys Cys Glu Cys Cys Asn Cys Gly Cys Tyr 1 5 10 <210> 214 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 214 Cys Cys Glu Cys Cys Asn Cys Thr Cys Tyr 1 5 10 <210> 215 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 215 Cys Cys Glu Cys Cys Asn Cys Thr Gly Cys 1 5 10 <210> 216 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 216 Cys Cys Glu Cys Cys Asn Ala Cys Gly Cys Tyr 1 5 10 <210> 217 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 217 Cys Cys Glu Cys Cys Asn Ala Cys Cys Tyr 1 5 10 <210> 218 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 218 Cys Cys Glu Cys Cys Asn Ala Cys Gly Cys 1 5 10 <210> 219 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 219 Cys Cys Glu Cys Cys Asn Ala Cys Thr Cys Tyr 1 5 10 <210> 220 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 220 Cys Cys Glu Cys Cys Asn Ala Cys Thr Cys 1 5 10 <210> 221 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 221 Cys Cys Glu Cys Cys Asn Ala Cys Thr Gly Cys 1 5 10 <210> 222 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 222 Cys Cys Glu Cys Cys Asn Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 223 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 223 Cys Cys Glu Cys Cys Asn Pro Cys Gly Cys Tyr 1 5 10 <210> 224 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 224 Cys Cys Glu Cys Cys Asn Pro Cys Cys Tyr 1 5 10 <210> 225 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 225 Cys Cys Glu Cys Cys Asn Pro Cys Gly Cys 1 5 10 <210> 226 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 226 Cys Cys Glu Cys Cys Asn Pro Cys Thr Cys Tyr 1 5 10 <210> 227 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 227 Cys Cys Glu Cys Cys Asn Pro Cys Thr Cys 1 5 10 <210> 228 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 228 Cys Cys Glu Cys Cys Asn Pro Cys Thr Gly Cys 1 5 10 <210> 229 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 229 Cys Cys Glu Cys Cys Asn Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 230 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 230 Cys Cys Glu Cys Cys Asn Pro Ala Cys Cys Tyr 1 5 10 <210> 231 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 231 Cys Cys Glu Cys Cys Asn Pro Ala Cys Cys 1 5 10 <210> 232 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 232 Cys Cys Glu Cys Cys Asn Pro Ala Cys Gly Cys 1 5 10 <210> 233 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 233 Cys Cys Glu Cys Cys Asn Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 234 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 234 Cys Cys Glu Cys Cys Asn Pro Ala Cys Thr Cys 1 5 10 <210> 235 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 235 Cys Cys Glu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 236 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 236 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 237 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 237 Cys Cys Glu Tyr Cys Cys Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 238 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 238 Cys Cys Glu Tyr Cys Cys Cys Thr Gly Cys Tyr 1 5 10 <210> 239 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 239 Cys Cys Glu Tyr Cys Cys Cys Gly Cys Tyr 1 5 10 <210> 240 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 240 Cys Cys Glu Tyr Cys Cys Cys Thr Cys Tyr 1 5 10 <210> 241 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 241 Cys Cys Glu Tyr Cys Cys Cys Thr Gly Cys 1 5 10 <210> 242 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 242 Cys Cys Glu Tyr Cys Cys Ala Cys Gly Cys Tyr 1 5 10 <210> 243 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 243 Cys Cys Glu Tyr Cys Cys Ala Cys Cys Tyr 1 5 10 <210> 244 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 244 Cys Cys Glu Tyr Cys Cys Ala Cys Gly Cys 1 5 10 <210> 245 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 245 Cys Cys Glu Tyr Cys Cys Ala Cys Thr Cys Tyr 1 5 10 <210> 246 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 246 Cys Cys Glu Tyr Cys Cys Ala Cys Thr Cys 1 5 10 <210> 247 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 247 Cys Cys Glu Tyr Cys Cys Ala Cys Thr Gly Cys 1 5 10 <210> 248 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 248 Cys Cys Glu Tyr Cys Cys Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 249 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 249 Cys Cys Glu Tyr Cys Cys Pro Cys Gly Cys Tyr 1 5 10 <210> 250 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 250 Cys Cys Glu Tyr Cys Cys Pro Cys Cys Tyr 1 5 10 <210> 251 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 251 Cys Cys Glu Tyr Cys Cys Pro Cys Gly Cys 1 5 10 <210> 252 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 252 Cys Cys Glu Tyr Cys Cys Pro Cys Thr Cys Tyr 1 5 10 <210> 253 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 253 Cys Cys Glu Tyr Cys Cys Pro Cys Thr Cys 1 5 10 <210> 254 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 254 Cys Cys Glu Tyr Cys Cys Pro Cys Thr Gly Cys 1 5 10 <210> 255 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 255 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 256 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 256 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Cys Tyr 1 5 10 <210> 257 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 257 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Cys 1 5 10 <210> 258 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 258 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Gly Cys 1 5 10 <210> 259 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 259 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 260 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 260 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Thr Cys 1 5 10 <210> 261 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 261 Cys Cys Glu Tyr Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 262 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 262 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 263 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 263 Cys Cys Glu Tyr Cys Cys Asn Cys Thr Gly Cys Tyr 1 5 10 <210> 264 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 264 Cys Cys Glu Tyr Cys Cys Asn Cys Gly Cys Tyr 1 5 10 <210> 265 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 265 Cys Cys Glu Tyr Cys Cys Asn Cys Cys Tyr 1 5 10 <210> 266 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 266 Cys Cys Glu Tyr Cys Cys Asn Cys Gly Cys 1 5 10 <210> 267 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 267 Cys Cys Glu Tyr Cys Cys Asn Cys Thr Cys Tyr 1 5 10 <210> 268 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 268 Cys Cys Glu Tyr Cys Cys Asn Cys Thr Cys 1 5 10 <210> 269 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 269 Cys Cys Glu Tyr Cys Cys Asn Cys Thr Gly Cys 1 5 10 <210> 270 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 270 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Gly Cys Tyr 1 5 10 <210> 271 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 271 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Cys Tyr 1 5 10 <210> 272 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 272 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Cys 1 5 10 <210> 273 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 273 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Gly Cys 1 5 10 <210> 274 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 274 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Thr Cys Tyr 1 5 10 <210> 275 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 275 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Thr Cys 1 5 10 <210> 276 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 276 Cys Cys Glu Tyr Cys Cys Asn Ala Cys Thr Gly Cys 1 5 10 <210> 277 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 277 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Thr Gly Cys Tyr 1 5 10 <210> 278 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 278 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Gly Cys Tyr 1 5 10 <210> 279 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 279 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Cys Tyr 1 5 10 <210> 280 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 280 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Cys 1 5 10 <210> 281 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 281 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Gly Cys 1 5 10 <210> 282 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 282 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Thr Cys Tyr 1 5 10 <210> 283 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 283 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Thr Cys 1 5 10 <210> 284 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 284 Cys Cys Glu Tyr Cys Cys Asn Pro Cys Thr Gly Cys 1 5 10 <210> 285 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 285 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Cys Tyr 1 5 10 <210> 286 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 286 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Cys Tyr 1 5 10 <210> 287 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 287 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Cys 1 5 10 <210> 288 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 288 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Cys 1 5 10 <210> 289 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 289 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Cys Tyr 1 5 10 <210> 290 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 290 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Cys 1 5 10 <210> 291 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 291 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 292 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(13) <223> Xaa = Any Amino Acid <400> 292 Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 293 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 293 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 294 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 294 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 295 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 295 Cys Cys Xaa Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 296 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 296 Cys Cys Xaa Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 297 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 297 Cys Cys Xaa Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 298 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 298 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 299 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 299 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 300 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 300 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 301 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 301 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 302 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 302 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 303 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 303 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 304 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 304 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 305 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 305 Cys Cys Xaa Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 306 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 306 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 307 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 307 Cys Cys Xaa Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 308 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 308 Cys Cys Xaa Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 309 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 309 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 310 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 310 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 311 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 311 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 312 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 312 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 313 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 313 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 314 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 314 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 315 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 315 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 316 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 316 Cys Cys Xaa Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 317 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 317 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 318 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 318 Cys Cys Xaa Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 319 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 319 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 320 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 320 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 321 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 321 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 322 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 322 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 323 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 323 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 324 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 324 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 325 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 325 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 326 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 326 Cys Cys Xaa Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 327 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 327 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 328 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 328 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 329 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 329 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 330 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 330 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 331 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 331 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 332 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 332 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 333 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 333 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 334 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 334 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 335 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 335 Cys Cys Xaa Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 336 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 336 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 337 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 337 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 338 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 338 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 339 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 339 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 340 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 340 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 341 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 341 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 342 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 342 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 343 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 343 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 344 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 344 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 345 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 345 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 346 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 346 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 347 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 347 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 348 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 348 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 349 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 349 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 350 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 350 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 351 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 351 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 352 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 352 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 353 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 353 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 354 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 354 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 355 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 355 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 356 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 356 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 357 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 357 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 358 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 358 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 359 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 359 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 360 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 360 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 361 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 361 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 362 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 362 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 363 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 363 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 364 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 364 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 365 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 365 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 366 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 366 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 367 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 367 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 368 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 368 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 369 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 369 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 370 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 370 Cys Cys Xaa Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 371 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 371 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 372 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 372 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 373 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 373 Cys Cys Xaa Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 374 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 374 Cys Cys Xaa Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 375 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 375 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 376 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 376 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 377 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 377 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 378 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 378 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 379 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 379 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 380 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 380 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 381 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 381 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 382 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 382 Cys Cys Xaa Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 383 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 383 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 384 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 384 Cys Cys Xaa Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 385 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 385 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 386 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 386 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 387 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 387 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 388 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 388 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 389 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 389 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 390 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 390 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 391 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 391 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 392 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 392 Cys Cys Xaa Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 393 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 393 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 394 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 394 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 395 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 395 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 396 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 396 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 397 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 397 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 398 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 398 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 399 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 399 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 400 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 400 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 401 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 401 Cys Cys Xaa Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 402 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 402 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 403 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 403 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 404 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 404 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 405 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 405 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 406 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 406 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 407 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 407 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 408 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 408 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 409 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 409 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 410 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 410 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 411 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 411 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 412 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 412 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 413 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 413 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 414 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 414 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 415 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 415 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 416 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 416 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 417 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 417 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 418 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 418 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 419 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 419 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 420 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 420 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 421 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 421 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 422 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 422 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 423 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 423 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 424 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 424 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 425 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 425 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 426 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 426 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 427 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 427 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 428 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 428 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 429 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 429 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 430 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 430 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 431 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 431 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 432 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 432 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 433 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 433 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 434 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 434 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 435 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 435 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 436 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 436 Cys Cys Xaa Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 437 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 437 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 438 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 438 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 439 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 439 Cys Cys Xaa Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 440 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 440 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 441 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 441 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 442 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 442 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 443 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 443 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 444 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 444 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 445 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 445 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 446 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 446 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 447 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 447 Cys Cys Xaa Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 448 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 448 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 449 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 449 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 450 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 450 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 451 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 451 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 452 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 452 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 453 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 453 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 454 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 454 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 455 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 455 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 456 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 456 Cys Cys Xaa Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 457 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 457 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 458 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 458 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 459 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 459 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 460 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 460 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 461 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 461 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 462 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 462 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 463 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 463 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 464 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 464 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 465 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 465 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 466 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 466 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 467 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 467 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 468 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 468 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 469 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 469 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 470 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 470 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 471 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 471 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 472 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 472 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 473 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 473 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 474 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 474 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 475 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 475 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 476 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 476 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 477 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 477 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 478 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 478 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 479 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 479 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 480 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 480 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 481 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 481 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 482 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 482 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 483 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 483 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 484 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 484 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 485 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 485 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 486 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 486 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 487 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 487 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 488 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 488 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 489 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 489 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 490 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 490 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 491 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 491 Cys Cys Xaa Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 492 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 492 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 493 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 493 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 494 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 494 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 495 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 495 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 496 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 496 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 497 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 497 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 498 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 498 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 499 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 499 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 500 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 500 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 501 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 501 Cys Cys Xaa Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 502 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 502 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 503 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 503 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 504 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 504 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 505 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 505 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 506 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 506 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 507 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 507 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 508 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 508 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 509 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 509 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 510 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 510 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 511 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 511 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 512 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 512 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 513 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 513 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 514 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 514 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 515 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 515 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 516 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 516 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 517 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 517 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 518 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 518 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 519 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 519 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 520 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 520 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 521 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 521 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 522 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 522 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 523 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 523 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 524 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 524 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 525 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 525 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 526 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 526 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 527 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 527 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 528 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 528 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 529 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 529 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 530 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 530 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 531 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 531 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 532 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 532 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 533 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 533 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 534 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 534 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 535 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 535 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 536 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 536 Cys Cys Xaa Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 537 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 537 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 538 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 538 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 539 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 539 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 540 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 540 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 541 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 541 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 542 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 542 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 543 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 543 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 544 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 544 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 545 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 545 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 546 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 546 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 547 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 547 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 548 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 548 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 549 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 549 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 550 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 550 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 551 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 551 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 552 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 552 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 553 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 553 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 554 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 554 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 555 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 555 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 556 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 556 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 557 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 557 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 558 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 558 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 559 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 559 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 560 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 560 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 561 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 561 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 562 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 562 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 563 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 563 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 564 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 564 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 565 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 565 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 566 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 566 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 567 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 567 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 568 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 568 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 569 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 569 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 570 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 570 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 571 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 571 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 572 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 572 Cys Cys Xaa Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 573 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 573 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 574 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 574 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 575 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 575 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 576 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 576 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 577 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 577 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 578 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 578 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 579 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 579 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 580 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 580 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 581 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 581 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 582 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 582 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 583 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 583 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 584 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 584 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 585 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 585 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 586 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 586 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 587 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 587 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 588 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 588 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 589 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 589 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 590 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 590 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 591 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 591 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 592 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 592 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 593 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 593 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 594 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 594 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 595 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 595 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 596 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 596 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 597 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 597 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 598 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 598 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 599 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 599 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 600 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 600 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 601 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 601 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 602 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 602 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 603 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 603 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 604 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 604 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 605 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 605 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 606 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 606 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 607 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 607 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 608 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 608 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 609 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 609 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 610 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 610 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 611 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 611 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 612 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 612 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 613 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 613 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 614 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 614 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 615 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 615 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 616 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 616 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 617 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 617 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 618 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 618 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 619 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 619 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 620 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 620 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 621 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 621 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 622 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 622 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 623 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 623 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 624 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 624 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 625 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 625 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 626 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 626 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 627 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 627 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 628 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 628 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 629 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 629 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 630 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 630 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 631 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 631 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 632 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 632 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 633 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 633 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 634 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 634 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 635 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 635 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 636 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 636 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 637 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 637 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 638 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 638 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 639 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 639 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 640 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 640 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 641 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 641 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 642 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 642 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 643 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 643 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 644 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 644 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 645 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 645 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 646 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 646 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 647 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 647 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 648 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 648 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 649 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 649 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 650 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 650 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 651 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 651 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 652 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 652 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 653 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 653 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 654 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 654 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 655 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 655 Cys Cys Xaa Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 656 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 656 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 657 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 657 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 658 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 658 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 659 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 659 Cys Cys Glu Xaa Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 660 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 660 Cys Cys Glu Xaa Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 661 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 661 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 662 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 662 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 663 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 663 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 664 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 664 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 665 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 665 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 666 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 666 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 667 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 667 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 668 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 668 Cys Cys Glu Xaa Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 669 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 669 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 670 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 670 Cys Cys Glu Xaa Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 671 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 671 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 672 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 672 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 673 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 673 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 674 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 674 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 675 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 675 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 676 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 676 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 677 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 677 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 678 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 678 Cys Cys Glu Xaa Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 679 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 679 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 680 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 680 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 681 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 681 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 682 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 682 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 683 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 683 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 684 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 684 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 685 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 685 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 686 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 686 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 687 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 687 Cys Cys Glu Xaa Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 688 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 688 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 689 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 689 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 690 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 690 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 691 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 691 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 692 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 692 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 693 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 693 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 694 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 694 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 695 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 695 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 696 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 696 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 697 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 697 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 698 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 698 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 699 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 699 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 700 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 700 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 701 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 701 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 702 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 702 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 703 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 703 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 704 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 704 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 705 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 705 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 706 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 706 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 707 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 707 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 708 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 708 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 709 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 709 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 710 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 710 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 711 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 711 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 712 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 712 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 713 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 713 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 714 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 714 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 715 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 715 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 716 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 716 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 717 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 717 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 718 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 718 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 719 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 719 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 720 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 720 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 721 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 721 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 722 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 722 Cys Cys Glu Xaa Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 723 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 723 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 724 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 724 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 725 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 725 Cys Cys Glu Xaa Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 726 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 726 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 727 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 727 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 728 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 728 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 729 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 729 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 730 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 730 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 731 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 731 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 732 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 732 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 733 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 733 Cys Cys Glu Xaa Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 734 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 734 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 735 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 735 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 736 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 736 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 737 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 737 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 738 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 738 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 739 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 739 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 740 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 740 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 741 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 741 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 742 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 742 Cys Cys Glu Xaa Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 743 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 743 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 744 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 744 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 745 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 745 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 746 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 746 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 747 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 747 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 748 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 748 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 749 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 749 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 750 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 750 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 751 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 751 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 752 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 752 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 753 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 753 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 754 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 754 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 755 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 755 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 756 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 756 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 757 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 757 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 758 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 758 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 759 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 759 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 760 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 760 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 761 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 761 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 762 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 762 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 763 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 763 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 764 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 764 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 765 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 765 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 766 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 766 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 767 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 767 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 768 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 768 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 769 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 769 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 770 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 770 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 771 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 771 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 772 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 772 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 773 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 773 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 774 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 774 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 775 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 775 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 776 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 776 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 777 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 777 Cys Cys Glu Xaa Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 778 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 778 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 779 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 779 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 780 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 780 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 781 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 781 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 782 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 782 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 783 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 783 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 784 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 784 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 785 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 785 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 786 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 786 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 787 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 787 Cys Cys Glu Xaa Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 788 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 788 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 789 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 789 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 790 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 790 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 791 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 791 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 792 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 792 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 793 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 793 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 794 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 794 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 795 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 795 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 796 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 796 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 797 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 797 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 798 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 798 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 799 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 799 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 800 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 800 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 801 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 801 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 802 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 802 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 803 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 803 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 804 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 804 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 805 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 805 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 806 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 806 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 807 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 807 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 808 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 808 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 809 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 809 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 810 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 810 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 811 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 811 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 812 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 812 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 813 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 813 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 814 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 814 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 815 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 815 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 816 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 816 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 817 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 817 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 818 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 818 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 819 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 819 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 820 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 820 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 821 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 821 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 822 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 822 Cys Cys Glu Xaa Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 823 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 823 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 824 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 824 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 825 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 825 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 826 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 826 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 827 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 827 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 828 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 828 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 829 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 829 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 830 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 830 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 831 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 831 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 832 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 832 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 833 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 833 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 834 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 834 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 835 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 835 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 836 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 836 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 837 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 837 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 838 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 838 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 839 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 839 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 840 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 840 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 841 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 841 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 842 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 842 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 843 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 843 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 844 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 844 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 845 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 845 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 846 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 846 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 847 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 847 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 848 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 848 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 849 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 849 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 850 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 850 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 851 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 851 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 852 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 852 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 853 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 853 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 854 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 854 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 855 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 855 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 856 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 856 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 857 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 857 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 858 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 858 Cys Cys Glu Xaa Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 859 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 859 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 860 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 860 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 861 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 861 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 862 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 862 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 863 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 863 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 864 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 864 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 865 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 865 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 866 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 866 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 867 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 867 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 868 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 868 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 869 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 869 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 870 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 870 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 871 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 871 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 872 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 872 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 873 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 873 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 874 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 874 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 875 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 875 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 876 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 876 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 877 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 877 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 878 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 878 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 879 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 879 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 880 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 880 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 881 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 881 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 882 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 882 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 883 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 883 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 884 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 884 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 885 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 885 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 886 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 886 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 887 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 887 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 888 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 888 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 889 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 889 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 890 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 890 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 891 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 891 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 892 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 892 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 893 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 893 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 894 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 894 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 895 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 895 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 896 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 896 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 897 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 897 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 898 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 898 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 899 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 899 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 900 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 900 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 901 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 901 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 902 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 902 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 903 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 903 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 904 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 904 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 905 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 905 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 906 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 906 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 907 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 907 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 908 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 908 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 909 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 909 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 910 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 910 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 911 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 911 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 912 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 912 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 913 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 913 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 914 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 914 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 915 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 915 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 916 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 916 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 917 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 917 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 918 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 918 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 919 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 919 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 920 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 920 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 921 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 921 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 922 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 922 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 923 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 923 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 924 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 924 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 925 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 925 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 926 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 926 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 927 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 927 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 928 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 928 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 929 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 929 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 930 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 930 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 931 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 931 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 932 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 932 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 933 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 933 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 934 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 934 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 935 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 935 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 936 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 936 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 937 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 937 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 938 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 938 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 939 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 939 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 940 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 940 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 941 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 941 Cys Cys Glu Xaa Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 942 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 942 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 943 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 943 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 944 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 944 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 945 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 945 Cys Cys Glu Tyr Xaa Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 946 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 946 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 947 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 947 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 948 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 948 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 949 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 949 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 950 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 950 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 951 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 951 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 952 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 952 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 953 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 953 Cys Cys Glu Tyr Xaa Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 954 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 954 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 955 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 955 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 956 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 956 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 957 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 957 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 958 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 958 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 959 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 959 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 960 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 960 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 961 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 961 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 962 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 962 Cys Cys Glu Tyr Xaa Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 963 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 963 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 964 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 964 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 965 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 965 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 966 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 966 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 967 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 967 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 968 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 968 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 969 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 969 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 970 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 970 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 971 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 971 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 972 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 972 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 973 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 973 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 974 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 974 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 975 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 975 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 976 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 976 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 977 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 977 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 978 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 978 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 979 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 979 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 980 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 980 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 981 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 981 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 982 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 982 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 983 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 983 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 984 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 984 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 985 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 985 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 986 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 986 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 987 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 987 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 988 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 988 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 989 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 989 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 990 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 990 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 991 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 991 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 992 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 992 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 993 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 993 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 994 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 994 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 995 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 995 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 996 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 996 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 997 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 997 Cys Cys Glu Tyr Xaa Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 998 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 998 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 999 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 999 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1000 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1000 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1001 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1001 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1002 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1002 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1003 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1003 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1004 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1004 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1005 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1005 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1006 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1006 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1007 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1007 Cys Cys Glu Tyr Xaa Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1008 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1008 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1009 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1009 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1010 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1010 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1011 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1011 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1012 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1012 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1013 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1013 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1014 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1014 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1015 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1015 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1016 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1016 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1017 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1017 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1018 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1018 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1019 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1019 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1020 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1020 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1021 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1021 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1022 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1022 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1023 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1023 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1024 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1024 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1025 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1025 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1026 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1026 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1027 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1027 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1028 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1028 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1029 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1029 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1030 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1030 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1031 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1031 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1032 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1032 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1033 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1033 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1034 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1034 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1035 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1035 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1036 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1036 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1037 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1037 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1038 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1038 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1039 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1039 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1040 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1040 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1041 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1041 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1042 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1042 Cys Cys Glu Tyr Xaa Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1043 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1043 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1044 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1044 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1045 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1045 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1046 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1046 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1047 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1047 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1048 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1048 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1049 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1049 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1050 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1050 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1051 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1051 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1052 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1052 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1053 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1053 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1054 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1054 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1055 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1055 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1056 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1056 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1057 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1057 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1058 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1058 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1059 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1059 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1060 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1060 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1061 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1061 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1062 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1062 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1063 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1063 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1064 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1064 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1065 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1065 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1066 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1066 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1067 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1067 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1068 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1068 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1069 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1069 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1070 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1070 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1071 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1071 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1072 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1072 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1073 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1073 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1074 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1074 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1075 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1075 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1076 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1076 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1077 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1077 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1078 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1078 Cys Cys Glu Tyr Xaa Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1079 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1079 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1080 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1080 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1081 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1081 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1082 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1082 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1083 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1083 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1084 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1084 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1085 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1085 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1086 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1086 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1087 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1087 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1088 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1088 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1089 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1089 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1090 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1090 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1091 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1091 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1092 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1092 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1093 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1093 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1094 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1094 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1095 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1095 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1096 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1096 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1097 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1097 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1098 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1098 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1099 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1099 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1100 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1100 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1101 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1101 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1102 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1102 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1103 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1103 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1104 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1104 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1105 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1105 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1106 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1106 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1107 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1107 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1108 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1108 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1109 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1109 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1110 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1110 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1111 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1111 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1112 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1112 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1113 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1113 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1114 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1114 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1115 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1115 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1116 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1116 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1117 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1117 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1118 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1118 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1119 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1119 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1120 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1120 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1121 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1121 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1122 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1122 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1123 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1123 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1124 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1124 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1125 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1125 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1126 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1126 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1127 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1127 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1128 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1128 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1129 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1129 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1130 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1130 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1131 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1131 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1132 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1132 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1133 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1133 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1134 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1134 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1135 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1135 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1136 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1136 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1137 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1137 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1138 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1138 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1139 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1139 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1140 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1140 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1141 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1141 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1142 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1142 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1143 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1143 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1144 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1144 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1145 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1145 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1146 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1146 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1147 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1147 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1148 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1148 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1149 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1149 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1150 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1150 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1151 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1151 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1152 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1152 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1153 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1153 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1154 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1154 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1155 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1155 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1156 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1156 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1157 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1157 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1158 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1158 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1159 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1159 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1160 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1160 Cys Cys Glu Tyr Xaa Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1161 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1161 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1162 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1162 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1163 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1163 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1164 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1164 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1165 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1165 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1166 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1166 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1167 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1167 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1168 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1168 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1169 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1169 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1170 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1170 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1171 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1171 Cys Cys Glu Tyr Cys Cys Xaa Xaa Xaa Asn Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1172 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1172 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1173 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1173 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1174 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1174 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1175 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1175 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1176 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1176 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1177 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1177 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1178 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1178 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1179 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1179 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1180 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1180 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1181 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1181 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1182 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1182 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1183 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1183 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1184 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1184 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1185 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1185 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1186 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1186 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1187 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1187 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1188 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1188 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1189 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1189 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1190 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1190 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1191 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1191 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1192 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1192 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1193 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1193 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1194 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1194 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1195 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1195 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1196 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1196 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1197 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1197 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1198 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1198 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1199 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1199 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1200 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1200 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1201 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1201 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1202 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1202 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1203 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1203 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1204 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1204 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1205 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1205 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1206 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1206 Cys Cys Glu Tyr Cys Cys Xaa Xaa Asn Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1207 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1207 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1208 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1208 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1209 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1209 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1210 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1210 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1211 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1211 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1212 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1212 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1213 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1213 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1214 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1214 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1215 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1215 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1216 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1216 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1217 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1217 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1218 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1218 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1219 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1219 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1220 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1220 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1221 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1221 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1222 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1222 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1223 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1223 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1224 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1224 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1225 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1225 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1226 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1226 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1227 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1227 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1228 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1228 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1229 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1229 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1230 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1230 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1231 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1231 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1232 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1232 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1233 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1233 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1234 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1234 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1235 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1235 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1236 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1236 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1237 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1237 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1238 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1238 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1239 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1239 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1240 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1240 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1241 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1241 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1242 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1242 Cys Cys Glu Tyr Cys Cys Xaa Asn Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1243 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1243 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1244 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1244 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1245 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1245 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1246 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1246 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1247 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1247 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1248 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1248 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1249 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1249 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1250 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1250 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1251 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1251 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1252 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1252 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1253 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1253 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1254 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1254 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1255 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1255 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1256 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1256 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1257 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1257 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1258 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1258 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1259 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1259 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1260 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1260 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1261 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1261 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1262 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1262 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1263 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1263 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1264 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1264 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1265 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1265 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1266 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1266 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1267 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1267 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1268 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1268 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1269 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1269 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1270 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1270 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1271 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1271 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1272 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1272 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1273 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1273 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1274 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1274 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1275 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1275 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1276 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1276 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1277 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1277 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1278 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1278 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1279 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1279 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1280 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1280 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1281 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1281 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1282 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1282 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1283 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1283 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1284 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1284 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1285 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1285 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1286 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1286 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1287 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1287 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1288 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1288 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1289 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1289 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1290 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1290 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1291 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1291 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1292 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1292 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1293 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1293 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1294 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1294 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1295 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1295 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1296 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1296 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1297 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1297 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1298 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1298 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1299 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1299 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1300 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1300 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1301 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1301 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1302 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1302 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1303 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1303 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1304 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1304 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1305 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1305 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1306 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1306 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1307 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1307 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1308 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1308 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1309 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1309 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1310 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1310 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1311 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1311 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1312 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1312 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1313 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1313 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1314 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1314 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1315 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1315 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1316 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1316 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1317 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1317 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1318 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1318 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1319 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1319 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1320 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1320 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1321 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1321 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1322 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1322 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1323 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1323 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1324 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1324 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1325 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1325 Cys Cys Glu Tyr Cys Cys Xaa Asn Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1326 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1326 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1327 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1327 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1328 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1328 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1329 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1329 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Xaa Pro Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1330 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1330 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1331 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1331 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1332 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1332 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1333 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1333 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1334 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1334 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1335 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1335 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Xaa Pro Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1336 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1336 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1337 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1337 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1338 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1338 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1339 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1339 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1340 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1340 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1341 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1341 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1342 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1342 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1343 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1343 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1344 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1344 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1345 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1345 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1346 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1346 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1347 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1347 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1348 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1348 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1349 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1349 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1350 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1350 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1351 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1351 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1352 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1352 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1353 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1353 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1354 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1354 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1355 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1355 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1356 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1356 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1357 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1357 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1358 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1358 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1359 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1359 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1360 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1360 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1361 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1361 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1362 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1362 Cys Cys Glu Tyr Cys Cys Asn Xaa Xaa Pro Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1363 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1363 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1364 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1364 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1365 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1365 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1366 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1366 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1367 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1367 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1368 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1368 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1369 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1369 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1370 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1370 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1371 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1371 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1372 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1372 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1373 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1373 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1374 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1374 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1375 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1375 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1376 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1376 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1377 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1377 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1378 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1378 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1379 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1379 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1380 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1380 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1381 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1381 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1382 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1382 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1383 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1383 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1384 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1384 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1385 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1385 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1386 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1386 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1387 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1387 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1388 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1388 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1389 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1389 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1390 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1390 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1391 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1391 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1392 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1392 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1393 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1393 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1394 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1394 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1395 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1395 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1396 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1396 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1397 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1397 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1398 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1398 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1399 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1399 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1400 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1400 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1401 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1401 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1402 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1402 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1403 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1403 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1404 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1404 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1405 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1405 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1406 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1406 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1407 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1407 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1408 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1408 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1409 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1409 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1410 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1410 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1411 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1411 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1412 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1412 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1413 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1413 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1414 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1414 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1415 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1415 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1416 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1416 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1417 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1417 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1418 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1418 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1419 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1419 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1420 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1420 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1421 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1421 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1422 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1422 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1423 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1423 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1424 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1424 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1425 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1425 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1426 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1426 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1427 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1427 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1428 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1428 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1429 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1429 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1430 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1430 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1431 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1431 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1432 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1432 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1433 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1433 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1434 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1434 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1435 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1435 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1436 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1436 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1437 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1437 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1438 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1438 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1439 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1439 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1440 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1440 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1441 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1441 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1442 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1442 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1443 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1443 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1444 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1444 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1445 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1445 Cys Cys Glu Tyr Cys Cys Asn Xaa Pro Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1446 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1446 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1447 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1447 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1448 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1448 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1449 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1449 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Xaa Ala Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1450 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1450 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1451 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1451 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1452 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1452 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1453 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1453 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1454 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1454 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Xaa Ala Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1455 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1455 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1456 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1456 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1457 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1457 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1458 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1458 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1459 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1459 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1460 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1460 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1461 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1461 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1462 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1462 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1463 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1463 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1464 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1464 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1465 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1465 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1466 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1466 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1467 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1467 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1468 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1468 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1469 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1469 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1470 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1470 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1471 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1471 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1472 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1472 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1473 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1473 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1474 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1474 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Xaa Ala Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1475 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1475 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1476 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1476 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1477 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1477 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1478 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1478 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1479 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1479 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1480 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1480 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1481 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1481 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1482 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1482 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1483 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1483 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1484 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1484 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1485 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1485 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1486 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1486 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1487 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1487 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1488 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1488 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1489 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1489 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1490 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1490 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1491 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1491 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1492 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1492 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1493 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1493 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1494 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1494 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1495 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1495 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1496 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1496 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1497 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1497 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1498 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1498 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1499 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1499 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1500 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1500 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1501 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1501 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1502 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1502 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1503 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1503 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1504 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1504 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1505 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1505 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1506 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1506 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1507 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1507 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1508 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1508 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1509 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1509 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1510 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1510 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1511 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1511 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1512 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1512 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1513 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1513 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1514 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1514 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1515 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1515 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1516 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1516 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1517 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1517 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1518 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1518 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1519 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1519 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1520 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1520 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1521 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1521 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1522 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1522 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1523 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1523 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1524 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1524 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1525 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1525 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1526 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1526 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1527 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1527 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1528 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1528 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1529 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1529 Cys Cys Glu Tyr Cys Cys Asn Pro Xaa Ala Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1530 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1530 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1531 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1531 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys Tyr 1 5 10 15 <210> 1532 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1532 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Tyr <210> 1533 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1533 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Xaa Cys Thr Gly 1 5 10 15 Cys Tyr <210> 1534 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1534 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1535 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1535 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1536 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1536 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1537 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1537 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Xaa Cys Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1538 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1538 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1539 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1539 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1540 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1540 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1541 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1541 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1542 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1542 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1543 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1543 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1544 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1544 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1545 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1545 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1546 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1546 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1547 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1547 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1548 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1548 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1549 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1549 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1550 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1550 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1551 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1551 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Xaa Cys Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1552 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1552 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1553 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1553 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1554 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1554 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1555 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1555 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1556 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1556 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1557 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1557 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1558 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1558 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1559 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1559 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1560 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1560 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1561 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1561 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1562 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1562 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1563 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1563 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1564 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1564 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1565 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1565 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1566 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1566 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1567 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1567 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1568 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1568 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1569 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1569 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1570 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1570 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1571 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1571 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1572 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1572 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1573 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1573 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1574 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1574 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1575 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1575 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1576 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1576 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1577 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1577 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1578 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1578 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1579 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1579 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1580 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1580 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1581 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1581 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1582 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1582 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1583 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1583 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1584 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1584 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1585 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1585 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Xaa Cys Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1586 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1586 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1587 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1587 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys Tyr 1 5 10 15 <210> 1588 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1588 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly Cys 1 5 10 15 Tyr <210> 1589 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1589 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Xaa Thr Gly 1 5 10 15 Cys Tyr <210> 1590 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1590 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Xaa Gly 1 5 10 15 Cys Tyr <210> 1591 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1591 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly Xaa 1 5 10 15 Cys Tyr <210> 1592 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1592 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Xaa Thr Gly Cys 1 5 10 15 Xaa Tyr <210> 1593 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1593 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly Cys 1 5 10 15 Tyr <210> 1594 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1594 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1595 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1595 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1596 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1596 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1597 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1597 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa Cys 1 5 10 15 Tyr <210> 1598 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1598 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1599 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1599 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1600 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1600 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys Xaa 1 5 10 15 Tyr <210> 1601 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1601 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Xaa Thr Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1602 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1602 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1603 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1603 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1604 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1604 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1605 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1605 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1606 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1606 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1607 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1607 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1608 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1608 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1609 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1609 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1610 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1610 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1611 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1611 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1612 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1612 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1613 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1613 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1614 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1614 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1615 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1615 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1616 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1616 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1617 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1617 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1618 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1618 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1619 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1619 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1620 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1620 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Xaa Thr Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1621 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1621 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Tyr 1 5 10 15 <210> 1622 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1622 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys Tyr 1 5 10 15 <210> 1623 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1623 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly Cys 1 5 10 15 Tyr <210> 1624 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1624 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Xaa Gly 1 5 10 15 Cys Tyr <210> 1625 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1625 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly Xaa 1 5 10 15 Cys Tyr <210> 1626 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1626 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Xaa Gly Cys 1 5 10 15 Xaa Tyr <210> 1627 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1627 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa Cys 1 5 10 15 Tyr <210> 1628 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1628 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa Xaa 1 5 10 15 Cys Tyr <210> 1629 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1629 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Xaa Cys 1 5 10 15 Xaa Tyr <210> 1630 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1630 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys Xaa 1 5 10 15 Tyr <210> 1631 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1631 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Xaa Gly Cys Xaa 1 5 10 15 Xaa Tyr <210> 1632 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1632 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys Tyr 1 5 10 15 <210> 1633 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1633 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa Cys 1 5 10 15 Tyr <210> 1634 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1634 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1635 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1635 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1636 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1636 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys Xaa 1 5 10 15 Tyr <210> 1637 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1637 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1638 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1638 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa Tyr 1 5 10 15 <210> 1639 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1639 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa Xaa 1 5 10 15 Tyr <210> 1640 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1640 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Xaa Gly Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1641 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1641 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Tyr 1 5 10 15 <210> 1642 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1642 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys Tyr 1 5 10 15 <210> 1643 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1643 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa Cys 1 5 10 15 Tyr <210> 1644 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1644 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa Xaa 1 5 10 15 Cys Tyr <210> 1645 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1645 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Xaa Cys 1 5 10 15 Xaa Tyr <210> 1646 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1646 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys Xaa 1 5 10 15 Tyr <210> 1647 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1647 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Xaa Cys Xaa 1 5 10 15 Xaa Tyr <210> 1648 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1648 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa Tyr 1 5 10 15 <210> 1649 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1649 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa Xaa 1 5 10 15 Tyr <210> 1650 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1650 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Xaa Cys Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1651 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(15) <223> Xaa = Any Amino Acid <400> 1651 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Tyr 1 5 10 15 <210> 1652 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(16) <223> Xaa = Any Amino Acid <400> 1652 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa Tyr 1 5 10 15 <210> 1653 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(17) <223> Xaa = Any Amino Acid <400> 1653 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa Xaa 1 5 10 15 Tyr <210> 1654 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <221> VARIANT <222> (1)...(18) <223> Xaa = Any Amino Acid <400> 1654 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa Xaa Xaa 1 5 10 15 Xaa Tyr <210> 1655 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1655 cacaccatat gaagaaatca atattattta tttttctttc tg 42 <210> 1656 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1656 cacacctcga gttaggtctc catgctttca ggaccacttt tattac 46 <210> 1657 <211> 69 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1657 gcatgaatag tagcaattac tgctgtgaat tgtgttgtaa tcctgcttgt accgggtgct 60 attaataac 69 <210> 1658 <211> 69 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1658 tcgagttatt aatagcaccc ggtacaagca ggattacaac acaattcaca gcagtaattg 60 ctactattc 69 <210> 1659 <211> 69 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1659 gcatgaatag tagcaattac tgctgtgaat attgttgtaa tcctgcttgt accgggtgct 60 attaataac 69 <210> 1660 <211> 69 <212> DNA <213> Artificial Sequence <220> <223> Synthetically generated oligonucleotide <400> 1660 tcgagttatt aatagcaccc ggtacaagca ggattacaac aatattcaca gcagtaattg 60 ctactattc 69 <210> 1661 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1661 Gln His Asn Pro Arg 1 5 <210> 1662 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1662 Val Gln His Asn Pro Arg 1 5 <210> 1663 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1663 Val Arg Gln His Asn Pro Arg 1 5 <210> 1664 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1664 Val Arg Gly Gln His Asn Pro Arg 1 5 <210> 1665 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1665 Val Arg Gly Pro Gln His Asn Pro Arg 1 5 <210> 1666 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1666 Val Arg Gly Pro Arg Gln His Asn Pro Arg 1 5 10 <210> 1667 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1667 Val Arg Gly Pro Arg Arg Gln His Asn Pro Arg 1 5 10 <210> 1668 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1668 Arg Gln His Asn Pro Arg 1 5 <210> 1669 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1669 Cys Cys Glu Leu Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1670 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1670 Cys Cys Glu Leu Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1671 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1671 Cys Cys Glu Leu Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1672 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1672 Cys Cys Glu Leu Cys Cys Ile Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1673 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1673 Cys Cys Glu Leu Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1674 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1674 Cys Cys Glu Leu Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1675 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1675 Cys Cys Glu Leu Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1676 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1676 Cys Cys Glu Leu Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1677 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1677 Cys Cys Glu Leu Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1678 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1678 Cys Cys Glu Leu Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1679 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1679 Cys Cys Glu Leu Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1680 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1680 Cys Cys Glu Leu Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1681 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1681 Cys Cys Glu Leu Cys Cys Gln Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1682 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1682 Cys Cys Glu Leu Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1683 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1683 Cys Cys Glu Leu Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1684 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1684 Cys Cys Glu Leu Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1685 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1685 Cys Cys Glu Leu Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1686 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1686 Cys Cys Glu Leu Cys Cys Arg Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210>1687 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1687 Cys Cys Glu Leu Cys Cys His Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1688 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1688 Cys Cys Glu Tyr Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1689 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1689 Cys Cys Glu Tyr Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1690 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1690 Cys Cys Glu Tyr Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1691 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1691 Cys Cys Glu Tyr Cys Cys Ile Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1692 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1692 Cys Cys Glu Tyr Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1693 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1693 Cys Cys Glu Tyr Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1694 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1694 Cys Cys Glu Tyr Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1695 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1695 Cys Cys Glu Tyr Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1696 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1696 Cys Cys Glu Tyr Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1697 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1697 Cys Cys Glu Tyr Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1698 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1698 Cys Cys Glu Tyr Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1699 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1699 Cys Cys Glu Tyr Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1700 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1700 Cys Cys Glu Tyr Cys Cys Gln Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1701 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1701 Cys Cys Glu Tyr Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1702 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1702 Cys Cys Glu Tyr Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1703 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1703 Cys Cys Glu Tyr Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1704 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1704 Cys Cys Glu Tyr Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1705 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1705 Cys Cys Glu Tyr Cys Cys Arg Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1706 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1706 Cys Cys Glu Tyr Cys Cys His Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1707 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1707 Cys Cys Glu Leu Cys Cys Ala Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1708 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1708 Cys Cys Glu Leu Cys Cys Val Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1709 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1709 Cys Cys Glu Leu Cys Cys Leu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1710 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1710 Cys Cys Glu Leu Cys Cys Ile Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1711 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1711 Cys Cys Glu Leu Cys Cys Pro Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1712 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1712 Cys Cys Glu Leu Cys Cys Met Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1713 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1713 Cys Cys Glu Leu Cys Cys Phe Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1714 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1714 Cys Cys Glu Leu Cys Cys Trp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1715 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1715 Cys Cys Glu Leu Cys Cys Gly Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1716 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1716 Cys Cys Glu Leu Cys Cys Ser Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1717 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1717 Cys Cys Glu Leu Cys Cys Thr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1718 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1718 Cys Cys Glu Leu Cys Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1719 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1719 Cys Cys Glu Leu Cys Cys Gln Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1720 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1720 Cys Cys Glu Leu Cys Cys Tyr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1721 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1721 Cys Cys Glu Leu Cys Cys Asp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1722 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1722 Cys Cys Glu Leu Cys Cys Glu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1723 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1723 Cys Cys Glu Leu Cys Cys Lys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1724 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1724 Cys Cys Glu Leu Cys Cys Arg Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1725 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1725 Cys Cys Glu Leu Cys Cys His Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1726 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1726 Cys Cys Glu Tyr Cys Cys Ala Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1727 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1727 Cys Cys Glu Tyr Cys Cys Val Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1728 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1728 Cys Cys Glu Tyr Cys Cys Leu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1729 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1729 Cys Cys Glu Tyr Cys Cys Ile Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1730 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1730 Cys Cys Glu Tyr Cys Cys Pro Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1731 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1731 Cys Cys Glu Tyr Cys Cys Met Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1732 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1732 Cys Cys Glu Tyr Cys Cys Phe Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1733 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1733 Cys Cys Glu Tyr Cys Cys Trp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1734 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1734 Cys Cys Glu Tyr Cys Cys Gly Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1735 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1735 Cys Cys Glu Tyr Cys Cys Ser Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1736 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1736 Cys Cys Glu Tyr Cys Cys Thr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1737 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1737 Cys Cys Glu Tyr Cys Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1738 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1738 Cys Cys Glu Tyr Cys Cys Gln Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1739 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1739 Cys Cys Glu Tyr Cys Cys Tyr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1740 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1740 Cys Cys Glu Tyr Cys Cys Asp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1741 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1741 Cys Cys Glu Tyr Cys Cys Glu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1742 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1742 Cys Cys Glu Tyr Cys Cys Lys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1743 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1743 Cys Cys Glu Tyr Cys Cys Arg Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1744 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1744 Cys Cys Glu Tyr Cys Cys His Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1745 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1745 Cys Cys Glu Leu Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr 1 5 10 <210> 1746 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1746 Cys Cys Glu Tyr Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr 1 5 10 <210> 1747 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1747 Cys Cys Glu Leu Cys Cys Asn Pro Thr Cys Thr Gly Cys 1 5 10 <210> 1748 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1748 Cys Cys Glu Tyr Cys Cys Asn Pro Thr Cys Thr Gly Cys 1 5 10 <210> 1749 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1749 Cys Cys Glu Phe Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr 1 5 10 <210> 1750 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1750 Cys Cys Glu Phe Cys Cys Asn Pro Thr Cys Thr Gly Cys 1 5 10 <210> 1751 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1751 Cys Cys Glu Trp Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr 1 5 10 <210> 1752 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1752 Cys Cys Glu Trp Cys Cys Asn Pro Thr Cys Thr Gly Cys 1 5 10 <210> 1753 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1753 Cys Cys Glu Leu Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1754 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1754 Cys Cys Glu Tyr Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1755 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1755 Cys Cys Glu Leu Cys Cys Asn Gly Ala Cys Thr Gly Cys 1 5 10 <210> 1756 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1756 Cys Cys Glu Tyr Cys Cys Asn Gly Ala Cys Thr Gly Cys 1 5 10 <210> 1757 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1757 Cys Cys Glu Phe Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1758 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1758 Cys Cys Glu Phe Cys Cys Asn Gly Ala Cys Thr Gly Cys 1 5 10 <210> 1759 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1759 Cys Cys Glu Trp Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1760 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1760 Cys Cys Glu Trp Cys Cys Asn Gly Ala Cys Thr Gly Cys 1 5 10 <210> 1761 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1761 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr 1 5 10 <210> 1762 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1762 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr 1 5 10 <210> 1763 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1763 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Val Gly Cys 1 5 10 <210> 1764 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1764 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Val Gly Cys 1 5 10 <210> 1765 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1765 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr 1 5 10 <210> 1766 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1766 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Val Gly Cys 1 5 10 <210> 1767 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1767 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr 1 5 10 <210>1768 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1768 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Val Gly Cys 1 5 10 <210>1769 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1769 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr 1 5 10 <210>1770 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1770 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr 1 5 10 <210>1771 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1771 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Gly Gly Cys 1 5 10 <210>1772 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1772 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Gly Cys 1 5 10 <210>1773 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1773 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr 1 5 10 <210>1774 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1774 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Gly Gly Cys 1 5 10 <210>1775 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1775 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr 1 5 10 <210>1776 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1776 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Gly Gly Cys 1 5 10 <210>1777 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1777 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr 1 5 10 <210>1778 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1778 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr 1 5 10 <210>1779 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1779 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Ala Cys 1 5 10 <210>1780 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1780 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Ala Cys 1 5 10 <210>1781 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1781 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr 1 5 10 <210>1782 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1782 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Ala Cys 1 5 10 <210>1783 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1783 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr 1 5 10 <210>1784 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1784 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Ala Cys 1 5 10 <210>1785 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1785 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala 1 5 10 <210>1786 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1786 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Val 1 5 10 <210>1787 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1787 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu 1 5 10 <210>1788 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1788 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Ile 1 5 10 <210>1789 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1789 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Pro 1 5 10 <210>1790 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1790 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Met 1 5 10 <210>1791 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1791 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe 1 5 10 <210>1792 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1792 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp 1 5 10 <210>1793 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1793 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly 1 5 10 <210>1794 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1794 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser 1 5 10 <210>1795 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1795 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr 1 5 10 <210>1796 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1796 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Cys 1 5 10 <210>1797 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1797 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Asn 1 5 10 <210>1798 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1798 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln 1 5 10 <210>1799 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1799 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp 1 5 10 <210>1800 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1800 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu 1 5 10 <210>1801 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1801 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys 1 5 10 <210>1802 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1802 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg 1 5 10 <210>1803 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1803 Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys His 1 5 10 <210>1804 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1804 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala 1 5 10 <210>1805 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1805 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Val 1 5 10 <210>1806 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1806 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu 1 5 10 <210>1807 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1807 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Ile 1 5 10 <210>1808 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1808 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Pro 1 5 10 <210> 1809 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1809 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Met 1 5 10 <210> 1810 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1810 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe 1 5 10 <210> 1811 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1811 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp 1 5 10 <210> 1812 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1812 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly 1 5 10 <210> 1813 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1813 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser 1 5 10 <210> 1814 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1814 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr 1 5 10 <210> 1815 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1815 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Cys 1 5 10 <210> 1816 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1816 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Asn 1 5 10 <210> 1817 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1817 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln 1 5 10 <210> 1818 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1818 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp 1 5 10 <210> 1819 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1819 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu 1 5 10 <210> 1820 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1820 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys 1 5 10 <210> 1821 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1821 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg 1 5 10 <210> 1822 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1822 Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys His 1 5 10 <210> 1823 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1823 Cys Cys Ala Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1824 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1824 Cys Cys Val Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1825 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1825 Cys Cys Leu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1826 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1826 Cys Cys Ile Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1827 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1827 Cys Cys Met Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1828 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1828 Cys Cys Phe Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1829 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1829 Cys Cys Trp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1830 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1830 Cys Cys Gly Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1831 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1831 Cys Cys Ser Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1832 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1832 Cys Cys Thr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1833 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1833 Cys Cys Cys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1834 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1834 Cys Cys Asn Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1835 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1835 Cys Cys Gln Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1836 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1836 Cys Cys Tyr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1837 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1837 Cys Cys Asp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1838 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1838 Cys Cys Lys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1839 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1839 Cys Cys Arg Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1840 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1840 Cys Cys His Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1841 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1841 Cys Cys Ala Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1842 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1842 Cys Cys Val Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1843 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1843 Cys Cys Leu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1844 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1844 Cys Cys Ile Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1845 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1845 Cys Cys Met Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1846 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1846 Cys Cys Phe Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1847 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1847 Cys Cys Trp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1848 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1848 Cys Cys Gly Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1849 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1849 Cys Cys Ser Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1850 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1850 Cys Cys Thr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1851 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1851 Cys Cys Cys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1852 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1852 Cys Cys Asn Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1853 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1853 Cys Cys Gln Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1854 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1854 Cys Cys Tyr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1855 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1855 Cys Cys Asp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1856 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1856 Cys Cys Lys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1857 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1857 Cys Cys Arg Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1858 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1858 Cys Cys His Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1859 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1859 Cys Cys Ala Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1860 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1860 Cys Cys Val Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1861 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1861 Cys Cys Leu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1862 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1862 Cys Cys Ile Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1863 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1863 Cys Cys Met Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1864 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1864 Cys Cys Phe Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1865 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1865 Cys Cys Trp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1866 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1866 Cys Cys Gly Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1867 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1867 Cys Cys Ser Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1868 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1868 Cys Cys Thr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1869 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1869 Cys Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1870 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1870 Cys Cys Asn Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1871 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1871 Cys Cys Gln Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1872 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1872 Cys Cys Tyr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1873 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1873 Cys Cys Asp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1874 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1874 Cys Cys Lys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1875 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1875 Cys Cys Arg Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1876 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1876 Cys Cys His Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1877 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1877 Cys Cys Ala Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1878 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1878 Cys Cys Val Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1879 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1879 Cys Cys Leu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1880 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1880 Cys Cys Ile Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1881 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1881 Cys Cys Met Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1882 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1882 Cys Cys Phe Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1883 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1883 Cys Cys Trp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1884 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1884 Cys Cys Gly Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1885 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1885 Cys Cys Ser Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1886 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1886 Cys Cys Thr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1887 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1887 Cys Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1888 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1888 Cys Cys Asn Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1889 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1889 Cys Cys Gln Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1890 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1890 Cys Cys Tyr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1891 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1891 Cys Cys Asp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1892 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1892 Cys Cys Lys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1893 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1893 Cys Cys Arg Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1894 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1894 Cys Cys His Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1895 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1895 Cys Cys Glu Phe Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1896 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1896 Cys Cys Glu Phe Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1897 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1897 Cys Cys Glu Phe Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1898 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1898 Cys Cys Glu Phe Cys Cys Ile Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1899 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1899 Cys Cys Glu Phe Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1900 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1900 Cys Cys Glu Phe Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1901 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1901 Cys Cys Glu Phe Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1902 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1902 Cys Cys Glu Phe Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1903 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1903 Cys Cys Glu Phe Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1904 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1904 Cys Cys Glu Phe Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1905 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1905 Cys Cys Glu Phe Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1906 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1906 Cys Cys Glu Phe Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1907 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1907 Cys Cys Glu Phe Cys Cys Gln Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1908 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1908 Cys Cys Glu Phe Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1909 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1909 Cys Cys Glu Phe Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1910 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1910 Cys Cys Glu Phe Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1911 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1911 Cys Cys Glu Phe Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1912 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1912 Cys Cys Glu Phe Cys Cys Arg Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1913 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1913 Cys Cys Glu Phe Cys Cys His Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1914 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1914 Cys Cys Glu Phe Cys Cys Ala Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1915 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1915 Cys Cys Glu Phe Cys Cys Val Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1916 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1916 Cys Cys Glu Phe Cys Cys Leu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1917 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1917 Cys Cys Glu Phe Cys Cys Ile Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1918 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1918 Cys Cys Glu Phe Cys Cys Pro Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1919 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1919 Cys Cys Glu Phe Cys Cys Met Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1920 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1920 Cys Cys Glu Phe Cys Cys Phe Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1921 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1921 Cys Cys Glu Phe Cys Cys Trp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1922 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1922 Cys Cys Glu Phe Cys Cys Gly Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1923 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1923 Cys Cys Glu Phe Cys Cys Ser Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1924 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1924 Cys Cys Glu Phe Cys Cys Thr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1925 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1925 Cys Cys Glu Phe Cys Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1926 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1926 Cys Cys Glu Phe Cys Cys Gln Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1927 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1927 Cys Cys Glu Phe Cys Cys Tyr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1928 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1928 Cys Cys Glu Phe Cys Cys Asp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1929 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1929 Cys Cys Glu Phe Cys Cys Glu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1930 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1930 Cys Cys Glu Phe Cys Cys Lys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1931 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1931 Cys Cys Glu Phe Cys Cys Arg Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1932 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1932 Cys Cys Glu Phe Cys Cys His Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1933 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1933 Cys Cys Glu Trp Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1934 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1934 Cys Cys Glu Trp Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1935 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1935 Cys Cys Glu Trp Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1936 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1936 Cys Cys Glu Trp Cys Cys Ile Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1937 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1937 Cys Cys Glu Trp Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1938 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1938 Cys Cys Glu Trp Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1939 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1939 Cys Cys Glu Trp Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1940 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1940 Cys Cys Glu Trp Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1941 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1941 Cys Cys Glu Trp Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1942 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1942 Cys Cys Glu Trp Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1943 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1943 Cys Cys Glu Trp Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1944 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1944 Cys Cys Glu Trp Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1945 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1945 Cys Cys Glu Trp Cys Cys Gln Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1946 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1946 Cys Cys Glu Trp Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1947 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1947 Cys Cys Glu Trp Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1948 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1948 Cys Cys Glu Trp Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1949 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1949 Cys Cys Glu Trp Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1950 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1950 Cys Cys Glu Trp Cys Cys Arg Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1951 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1951 Cys Cys Glu Trp Cys Cys His Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 1952 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1952 Cys Cys Glu Trp Cys Cys Ala Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1953 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1953 Cys Cys Glu Trp Cys Cys Val Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1954 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1954 Cys Cys Glu Trp Cys Cys Leu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1955 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1955 Cys Cys Glu Trp Cys Cys Ile Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1956 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1956 Cys Cys Glu Trp Cys Cys Pro Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1957 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1957 Cys Cys Glu Trp Cys Cys Met Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1958 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1958 Cys Cys Glu Trp Cys Cys Phe Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1959 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1959 Cys Cys Glu Trp Cys Cys Trp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1960 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1960 Cys Cys Glu Trp Cys Cys Gly Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1961 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1961 Cys Cys Glu Trp Cys Cys Ser Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1962 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1962 Cys Cys Glu Trp Cys Cys Thr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1963 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1963 Cys Cys Glu Trp Cys Cys Cys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1964 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1964 Cys Cys Glu Trp Cys Cys Gln Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1965 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1965 Cys Cys Glu Trp Cys Cys Tyr Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1966 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1966 Cys Cys Glu Trp Cys Cys Asp Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1967 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1967 Cys Cys Glu Trp Cys Cys Glu Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1968 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1968 Cys Cys Glu Trp Cys Cys Lys Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1969 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1969 Cys Cys Glu Trp Cys Cys Arg Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1970 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1970 Cys Cys Glu Trp Cys Cys His Pro Ala Cys Thr Gly Cys 1 5 10 <210> 1971 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1971 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala 1 5 10 <210> 1972 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1972 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Val 1 5 10 <210> 1973 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1973 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu 1 5 10 <210> 1974 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1974 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Ile 1 5 10 <210> 1975 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1975 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Pro 1 5 10 <210> 1976 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1976 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Met 1 5 10 <210> 1977 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1977 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe 1 5 10 <210> 1978 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1978 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp 1 5 10 <210> 1979 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1979 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly 1 5 10 <210> 1980 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1980 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser 1 5 10 <210> 1981 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1981 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr 1 5 10 <210> 1982 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1982 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Cys 1 5 10 <210> 1983 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1983 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Asn 1 5 10 <210> 1984 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1984 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln 1 5 10 <210> 1985 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1985 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp 1 5 10 <210> 1986 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1986 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu 1 5 10 <210> 1987 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1987 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys 1 5 10 <210> 1988 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1988 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg 1 5 10 <210> 1989 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1989 Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys His 1 5 10 <210> 1990 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1990 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala 1 5 10 <210> 1991 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1991 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Val 1 5 10 <210> 1992 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1992 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu 1 5 10 <210> 1993 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1993 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Ile 1 5 10 <210> 1994 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1994 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Pro 1 5 10 <210> 1995 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1995 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Met 1 5 10 <210> 1996 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1996 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe 1 5 10 <210> 1997 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1997 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp 1 5 10 <210> 1998 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1998 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly 1 5 10 <210> 1999 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 1999 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser 1 5 10 <210> 2000 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2000 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr 1 5 10 <210> 2001 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2001 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Cys 1 5 10 <210> 2002 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2002 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Asn 1 5 10 <210> 2003 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2003 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln 1 5 10 <210> 2004 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2004 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp 1 5 10 <210> 2005 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2005 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu 1 5 10 <210> 2006 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2006 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys 1 5 10 <210> 2007 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2007 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg 1 5 10 <210> 2008 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2008 Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys His 1 5 10 <210> 2009 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2009 Cys Cys Ala Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2010 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2010 Cys Cys Val Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2011 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2011 Cys Cys Leu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2012 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2012 Cys Cys Ile Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2013 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2013 Cys Cys Met Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2014 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2014 Cys Cys Phe Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2015 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2015 Cys Cys Trp Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2016 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2016 Cys Cys Gly Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2017 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2017 Cys Cys Ser Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2018 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2018 Cys Cys Thr Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2019 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2019 Cys Cys Cys Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2020 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2020 Cys Cys Asn Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2021 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2021 Cys Cys Gln Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2022 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2022 Cys Cys Tyr Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2023 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2023 Cys Cys Asp Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2024 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2024 Cys Cys Lys Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2025 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2025 Cys Cys Arg Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2026 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2026 Cys Cys His Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2027 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2027 Cys Cys Ala Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2028 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2028 Cys Cys Val Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2029 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2029 Cys Cys Leu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2030 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2030 Cys Cys Ile Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2031 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2031 Cys Cys Met Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2032 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2032 Cys Cys Phe Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2033 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2033 Cys Cys Trp Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2034 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2034 Cys Cys Gly Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2035 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2035 Cys Cys Ser Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2036 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2036 Cys Cys Thr Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2037 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2037 Cys Cys Cys Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2038 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2038 Cys Cys Asn Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2039 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2039 Cys Cys Gln Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2040 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2040 Cys Cys Tyr Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2041 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2041 Cys Cys Asp Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2042 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2042 Cys Cys Lys Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2043 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2043 Cys Cys Arg Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2044 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2044 Cys Cys His Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2045 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2045 Cys Cys Ala Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2046 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2046 Cys Cys Val Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2047 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2047 Cys Cys Leu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2048 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2048 Cys Cys Ile Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2049 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2049 Cys Cys Met Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2050 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2050 Cys Cys Phe Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2051 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2051 Cys Cys Trp Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2052 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2052 Cys Cys Gly Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2053 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2053 Cys Cys Ser Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2054 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2054 Cys Cys Thr Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2055 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2055 Cys Cys Cys Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2056 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2056 Cys Cys Asn Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2057 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2057 Cys Cys Gln Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2058 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2058 Cys Cys Tyr Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2059 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2059 Cys Cys Asp Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2060 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2060 Cys Cys Lys Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2061 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2061 Cys Cys Arg Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2062 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2062 Cys Cys His Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr 1 5 10 <210> 2063 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2063 Cys Cys Ala Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2064 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2064 Cys Cys Val Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2065 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2065 Cys Cys Leu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2066 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2066 Cys Cys Ile Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2067 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2067 Cys Cys Met Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2068 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2068 Cys Cys Phe Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2069 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2069 Cys Cys Trp Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2070 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2070 Cys Cys Gly Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2071 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2071 Cys Cys Ser Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2072 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2072 Cys Cys Thr Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2073 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2073 Cys Cys Cys Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2074 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2074 Cys Cys Asn Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2075 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2075 Cys Cys Gln Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2076 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2076 Cys Cys Tyr Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2077 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2077 Cys Cys Asp Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2078 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2078 Cys Cys Lys Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2079 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2079 Cys Cys Arg Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2080 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2080 Cys Cys His Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys 1 5 10 <210> 2081 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2081 Gly Asn Leu Ile Asp Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe 1 5 10 15 Gly Cys Leu Asn 20 <210> 2082 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2082 Gly Asn Leu Ile Asp Arg Cys Glu Ile Cys Cys Asn Pro Ala Cys Phe 1 5 10 15 Gly Cys Leu Asn 20 <210> 2083 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <400> 2083 Pro Pro Ala Glu Val Ser Ser Asp Trp Asp Cys Cys Asp Val Cys Cys 1 5 10 15 Asn Pro Ala Cys Ala Gly Cys 20 <210> 2084 <211> 65 <212> PRT <213> Artificial Sequence <220> <223> Synthetically generated peptide <220> <220> <221> VARIANT <222> 2-4, 7-10, 12-15, 17-20, 22-25, 27-30, 32-35, 37-40, 42-45, 47-50, 52-55, 57-60, 62-65 <223> Xaa = any amino acid (natural or non-natural), the same or diferent <400> 2084 Cys Xaa Xaa Xaa Xaa Glu Xaa Xaa Xaa Xaa Tyr Xaa Xaa Xaa Xaa Cys 1 5 10 15 Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Pro Xaa 20 25 30 Xaa Xaa Xaa Ala Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Thr Xaa Xaa 35 40 45 Xaa Xaa Gly Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Tyr Xaa Xaa Xaa 50 55 60 Xaa 65

Claims (23)

  1. 하기 아미노산 서열로 이루어진 폴리펩티드 또는 그의 약학적으로 허용가능한 염:
    Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys.
  2. 제1항에 있어서, 상기 폴리펩티드는 구아닐레이트 사이클라제 C 수용체를 활성화하는 것인 폴리펩티드.
  3. 제1항 또는 제2항에 따른 폴리펩티드를 포함하는 위장 장애 치료용 약학 조성물.
  4. 제3항에 있어서, 상기 위장 장애는 위장 운동 장애인 약학 조성물.
  5. 제3항에 있어서, 상기 위장 장애는 과민성 대장 증후군(irritable bowel syndrom), 변비, 기능성 위장 장애, 위식도 역류 질환, 기능성 속 쓰림(functional heartburn), 소화불량, 위부전마비(gastroparesis), 만성 가성 장 폐색(chronic intestinal pseudo-obstruction), 가성 대장폐색(colonic pseudo-obstruction), 크론병, 궤양성 직장염(ulcerative colitis), 및 염증성 장 질환으로 이루어진 군으로부터 선택되는 약학 조성물.
  6. 제1항 또는 제2항에 있어서, 변비 치료용 약학 조성물의 제조를 위해 사용되는 폴리펩티드.
  7. 제6항에 있어서, 상기 변비는 만성 변비인 폴리펩티드.
  8. 제6항에 있어서, 상기 변비는 특발성 변비인 폴리펩티드.
  9. 제6항에 있어서, 상기 변비는 수술 후 장폐색이 원인인 폴리펩티드.
  10. 제6항에 있어서, 상기 변비는 아편제의 사용에 의해 유발된 것인 폴리펩티드.
  11. 제1항 또는 제2항에 있어서, 위장 운동성의 증가를 위한 약학 조성물의 제조에 사용되는 폴리펩티드.
  12. 제1항 또는 제2항에 있어서, 과민성 대장 증후군 치료용 약학 조성물의 제조에 사용되는 폴리펩티드.
  13. 제12항에 있어서, 상기 과민성 대장 증후군은 교대성 과민성 대장 증후군(alternating irritable bowel syndrome)인 폴리펩티드.
  14. 제3항에 있어서, 경구 투여되는 약학 조성물.
  15. 제13항에 있어서, 상기 과민성 대장 증후군은 변비가 주증상인 과민성 대장 증후군인 폴리펩티드.
  16. 제1항 또는 제2항에 따른 폴리펩티드를 포함하는 변비 치료용 약학 조성물.
  17. 제16항에 있어서, 상기 변비는 만성 변비인 약학 조성물.
  18. 제16항에 있어서, 상기 변비는 특발성 변비인 약학 조성물.
  19. 제16항에 있어서, 상기 변비는 수술후 장폐색이 원인인 약학 조성물.
  20. 제16항에 있어서, 상기 변비는 아편제의 사용에 의해 유발된 것인 약학 조성물.
  21. 제1항 또는 제2항에 따른 폴리펩티드를 포함하는 과민성 대장 증후군 치료용 약학 조성물.
  22. 제21항에 있어서, 상기 과민성 대장 증후군은 변비가 주증상인 과민성 대장 증후군인 약학 조성물.
  23. 제21항에 있어서, 상기 과민성 대장 증후군은 교대성 과민성 대장 증후군(alternating irritable bowel syndrome)인 약학 조성물.
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CN102020704A (zh) 2011-04-20
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US7772188B2 (en) 2010-08-10
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CA2558050C (en) 2013-11-05
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