KR20230125802A - 신규 화합물 - Google Patents
신규 화합물 Download PDFInfo
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- KR20230125802A KR20230125802A KR1020237023291A KR20237023291A KR20230125802A KR 20230125802 A KR20230125802 A KR 20230125802A KR 1020237023291 A KR1020237023291 A KR 1020237023291A KR 20237023291 A KR20237023291 A KR 20237023291A KR 20230125802 A KR20230125802 A KR 20230125802A
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- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000004260 weight control Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
- 229960002911 zonisamide Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
본 발명은 펩티드 호르몬 유사체이고 당뇨병 및 비만과 같은 장애를 치료하는 데 유용한 신규 화합물을 제공한다. 본 명세서에 인용된 일반적인 서열의 화합물은 글루카곤 및 GLP-1 수용체에서의 효능 특성과 관련하여 맞춤형 프로파일을 갖는다. 생체내 특성과 관련하여, 본 발명의 예시 펩티드의 투여는 동물 모델에서 체중 감량을 높이는 것으로 나타났다. 바람직한 화합물은 음식 섭취를 유의적으로 감소시키지 않으면서 이를 달성한다.
Description
본 발명은 펩티드 호르몬 유사체인 화합물로서, 당뇨병 및 비만과 같은 장애를 치료하는 데 유용한 화합물에 관한 것이다.
미국국민건강영양조사(NHANES, 2009-2010)에 따르면, 미국에서 20세 이상 성인의 33.0%가 과체중이며, 35.7%가 비만이고, 6.3%는 고도비만이다. 또한, 미국에서 아동의 대다수가 과체중 또는 비만이다.
비만의 원인은 복잡하고 다인자성이다. 증가하는 증거는 비만이 단순한 자제력의 문제가 아니라 식욕 조절 및 에너지 대사와 관련된 복잡한 장애임을 시사한다. 또한, 비만은 집단에서의 이환율 및 사망률 증가와 관련된 다양한 상태와 관련이 있다. 비만의 원인이 명확하게 확립되지는 않았지만 유전적, 대사적, 생화학적, 문화적, 심리사회적 요인이 기여하는 것으로 여겨진다. 일반적으로 비만은 과도한 체지방이 개인을 건강 위험에 빠뜨리는 상태로서 기술되었다.
비만이 이환율 및 사망률 증가와 관련이 있다는 강력한 증거가 있다. 심혈관 질환 위험 및 제2형 당뇨병 질환 위험과 같은 질환 위험은 체질량 지수(BMI) 증가와 독립적으로 증가한다. 실제로 이러한 위험은 BMI가 24.9를 초과하는 경우 여성은 심장 질환 위험이 5% 증가하고 남성은 심장 질환 위험이 7% 증가하는 것으로 정량화되었다(문헌[Kenchaiah et al., N. Engl. J. Med. 347:305, 2002; Massie, N. Engl. J. Med. 347:358, 2002] 참조).
당뇨병은 불충분한 인슐린 분비 또는 표적 조직의 인슐린 저항성으로 인해 탄수화물, 단백질 및 지방 대사가 손상된 만성 증후군이다. 인슐린 의존성 진성 당뇨병(제1형 당뇨병)과 비인슐린 의존성 진성 당뇨병(제2형 당뇨병)의 두 가지 주요 형태로 발생한다.
제1형 당뇨병 또는 인슐린 의존성 진성 당뇨병(IDDM)은 β 세포의 파괴로 인해 발생하며, 이는 불충분한 내인성 인슐린 수준을 초래한다. 제2형 당뇨병 또는 비인슐린 의존성 당뇨병은 인슐린에 대한 신체의 민감성 결함과 인슐린 생성의 상대적 결핍으로부터 기인한다. 국립 당뇨병 통계 보고서에 따르면 2014년 미국의 20세 이상 성인 약 2,890만 명이 당뇨병을 앓고 있다(2012년 미국 인구 조사 데이터에 적용된 2009-2012년 국립건강영양조사 추정치). 성인의 경우 당뇨병의 90 내지 95%가 제2형 당뇨병이다.
비만인 사람의 체중 감소가 중요한 질환 위험 인자를 감소시킨다는 상당한 증거가 있다. 과체중 및 비만 성인 모두 초기 체중의 10%와 같은 약간의 체중 감소조차도 고혈압, 고지혈증 및 고혈당증과 같은 위험 인자의 감소와 관련이 있었다. 상당한 체중 감소가 제2형 당뇨병을 효과적으로 치료할 수 있는 것으로 나타났다(문헌[Lim et al., Diabetologia June 2011]).
식이요법과 운동이 체중 증가를 줄이는 간단한 과정을 제공하지만 과체중 및 비만인 개체는 종종 이러한 인자를 충분히 제어할 수 없어 효과적으로 체중을 감량할 수 없다. 약리학적 요법이 이용가능하고; 포괄적인 체중 감량 프로그램의 일부로 사용할 수 있는 몇 가지 체중 감량 약물이 미국식품의약국(Food and Drug Administration)의 승인을 받았다. 그러나 이러한 약물 중 상당수는 심각한 부작용을 갖는다. 덜 침습적인 방법이 실패하고 환자가 비만 관련 이환율 또는 사망률이 높은 경우, 체중 감량 수술은 임상적으로 심각한 비만 환자의 엄선된 선택지이다. 그러나 이러한 치료는 위험성이 높으며 제한된 수의 환자에게만 사용하기에 적합하다. 체중 감량을 원하는 것은 비만인 대상체만이 아니다. 권장 범위 내의, 예를 들어 권장 범위의 상단에 있는 체중을 가진 사람은 체중을 줄여서 이상적인 체중에 가까워지길 원할 수 있다. 따라서, 과체중 및 비만 대상 뿐만 아니라 정상 체중인 대상체에서 체중 감량을 달성하기 위해 사용될 수 있는 제제에 대한 요구가 남아 있다.
체중 감량에 유용한 제제의 개발에 대한 많은 접근법은 위장 펩티드 호르몬 및 그 유사체와 관련되어 있다. 예를 들어, 프리프로글루카곤 분자로부터 유도된 펩티드의 유도체는 비만 및/또는 당뇨병의 치료에 사용하기 위해 제안되었다. 프리프로글루카곤은 글루카곤 유사 펩티드 1(GLP-1)의 전구체 펩티드이며, 글루카곤 GLP-1을 비롯한 다른 호르몬은 장 내강에 있는 영양소의 존재에 반응하여 장 L 세포에서 생체 내에서 생성된다. GLP-1은 포도당 의존적 방식으로 췌장에서 인슐린 분비 증가, 췌장에서 글루카곤 분비 감소, 위 배출 억제, 포만감을 증가시켜 음식 섭취량 감소를 비롯하여 많은 생리적 기능을 가진다. 인슐린 분비가 증가하면 순환 포도당 농도가 감소한다.
이러한 펩티드의 유사체에 대한 연구의 예는 예를 들어 GLP-1 및 글루카곤 펩티드로부터의 서열을 함유하는 펩티드 분자를 기술하는 WO2013/004983호에 기재되어 있다. WO2015/132599호는 또한 프리프로글루카곤으로부터 유래되고 비만 및 당뇨병과 같은 장애의 치료에 유용한 펩티드 호르몬 유사체를 개시한다. WO2017/178829호는 변형된 리간드 편향 및 치료적으로 유용한 특성을 갖는 엑센딘-4, GLP-1 및 옥신토모듈린의 유사체인 화합물을 개시한다. 또 다른 예는 위치 34에서 아르기닌 잔기가 천연 라이신으로 치환되고 위치 26에서 라이신 잔기의 측쇄가 글루탐산 스페이서를 통해 라이신에 부착된 헥사데카노일기(팔미트산)에 의해 아실화된 GLP-1 (7-37)의 서열을 갖는 GLP-1 작용제인 펩티드 리라글루티드이다. 리라글루티드는 제2형 당뇨병 치료를 위해 1일 1회 주사가능한 약물로 사용하기 위해 개발되었다. 리라글루티드와 동일한 활성 성분이 비만 치료를 위해 Saxenda로 시판된다(1일 1회 주사). GLP-1의 주 1회 주사가능한 유사체인 세마글루티드는 인간 GLP-1(AIB8, Arg34)과 비교하여 두 개의 아미노산 치환을 가지며 링커 및 C18 이산 지방산으로 라이신 26에서 유도체화된다.
그러나 상당한 발전에도 불구하고 약물로 유용한 물질을 식별하는 과정은 여전히 복잡하고 많은 경우 예측할 수 없는 분야이다. 치료제로 유용하기 위해서는 화합물이 적절한 범위의 특성을 가져야 한다. 관심 생물학적 표적에서 양호한 효능을 갖는 것 외에도, 화합물은 양호한 생체내 약동학적 특성, 낮은 독성 및 허용가능한 부작용 프로파일을 가져야 한다. 예를 들어 리라글루티드와 같은 상용 제제를 사용해도 오심 및 구토 등의 부작용이 나타날 수 있으며 갑상선암 및 췌장염에 대한 우려도 제기되고 있다.
따라서, 당뇨병 및 비만과 같은 장애 및 질환의 치료에 유용한 추가 화합물에 대한 필요성이 남아있다. 예를 들어, 개선된 활성 프로파일과 같은 유익한 특성을 갖고/갖거나 부작용이 감소된 펩티드를 확인하는 것이 바람직할 것이다. 예를 들어, 식욕을 감소시키고/시키거나 음식 섭취량을 감소시키는 펩티드를 확인하는 것이 바람직할 것이다. 대안적으로 또는 추가로, 지속 기간 동안 이들 및 다른 생물학적 효과(예를 들어, 본 명세서에 기재된 치료적으로 유용한 생물학적 효과)를 갖는 펩티드를 확인하는 것이 바람직할 것이다. 더 긴 활성 기간을 갖는 화합물이 더 적은 빈도로 더 낮은 용량으로 투여될 수 있으며, 이는 대상체에 대한 편의성 개선, 부작용 감소 및 비용 절감에 기여한다.
제1 양태에서, 식 (I)의 화합물; 또는 화합물의 유도체; 또는 화합물 또는 유도체의 염 또는 용매화물이 제공된다:
Xaa1 -AIB2-Xaa3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Xaa10-Ser11 -Lys12-Gln13-Leu14-Glu15-Glu16-Xaa17-Xaa18-Val19-Xaa20-Xaa21 -Phe22-lle23-Glu24-Trp25-Leu26-Lys27-Xaa28-Xaa29-Gly30-Pro31-Ser32-Xaa33-Gly34-Xaa35-Xaa36-Pro37-Pro38-Xaa39-Xaa40-Xaa41 -Lys42 (I) [SEQ ID NO: 528]
상기 식에서,
Xaa1은 His, Tyr 또는 Phe이고;
Xaa3은 His, Gln 또는 Glu이고;
Xaa10은 Leu, Tyr 또는 Val이고;
Xaa17은 Glu 또는 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg, Gln, Lys 또는 His이고;
Xaa21은 Leu, Ala, Arg, Lys 또는 Glu이고;
Xaa28은 Ala, Asn, Gln 또는 His이고;
Xaa29는 Gly 또는 Ala이고;
Xaa33은 Ser, His 또는 Gln이고;
Xaa35는 Lys, Pro, His, Arg, Asn, Gln, Glu, Ser 또는 Ala이고;
Xaa36은 Phe, His, Gln, Glu, Lys, Ser, Arg이거나 부재하고;
Xaa39는 Pro 또는 Gly이고;
Xaa40은 Gly이거나 부재하고;
Xaa41은 Lys이거나 또는 부재하고;
위치 42에서의 라이신 잔기는 그의 ε-아미노기에서 기 Y로 치환되고, Y는
Z-Xaa43-Xaa44-이고,
상기 식에서,
Xaa43은 Asn이거나 부재하고;
Xaa44는 His이거나 부재하고;
Z는 하기 화학식의 기이다:
(여기서, R은 C16-C18 알킬렌 또는 알케닐렌 기이고;
R1은 CO2H임).
또한, 본 발명의 화합물, 유도체, 염 또는 용매화물을 약제학적으로 허용가능한 담체 및 선택적으로 추가의 치료제와 함께 포함하는 조성물이 본 명세서에 제공된다.
또한, 예를 들어 당뇨병, 비만, 심장 질환, 뇌졸중 또는 비-알코올성 지방간 질환의 예방 또는 치료에 사용하고, 대상체에서 인슐린 방출을 개선하고, 대상체에서 탄수화물 대사를 개선하고, 대상체에서 지질 프로파일을 개선하고, 대상체에서 식욕을 감소시키고, 음식 섭취량을 감소시키고, 칼로리 섭취를 감소시키고, 탄수화물 내성을 개선하기 위한, 및/또는 예를 들어 파킨슨병, 알츠하이머병 및 기타 유형의 신경 및 세포 변성의 예방 또는 치료에서 세포보호제로서 사용하기 위한 약제로서 사용하기 위한, 본 발명의 화합물, 유도체, 염 또는 용매화물, 또는 그러한 화합물, 유도체, 염 또는 용매화물 및 약제학적으로 허용가능한 담체를 포함하는 조성물이 본 명세서에 제공된다.
또한, 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 용매화물, 또는 그러한 화합물, 유도체, 염 또는 용매화물 및 약제학적으로 허용가능한 담체를 포함하는 조성물을 투여하는 단계를 포함하는 대상체에서 질환 또는 장애 또는 다른 원치 않는 생리학적 상태를 치료 또는 예방하는 방법, 예를 들어 대상체에서 당뇨병, 비만, 심장 질환, 뇌졸중 또는 비-알코올성 지방간 질환의 치료 또는 예방하고/하거나, 대상체에서 인슐린 방출을 개선하고/하거나, 대상체에서 탄수화물 대사를 개선하고/하거나, 대상체에서 지질 프로파일을 개선하고/하거나, 대상체에서 탄수화물 내성을 개선하고/하거나, 대상체에서 식욕을 감소시키고/시키거나, 음식 섭취량을 감소시키고/시키거나, 칼로리 섭취를 감소시키고/시키거나, 세포보호를 제공하는 방법이 본 명세서에 제공된다.
또한, 당뇨병, 비만, 심장 질환, 뇌졸중 또는 비-알코올성 지방간 질환을 예방 또는 치료하고, 대상체에서 인슐린 방출을 개선하고, 대상체에서 탄수화물 대사를 개선하고, 대상체에서 지질 프로파일을 개선하고, 대상체에서 탄수화물 내성을 감소하고, 대상체에서 식욕을 감소시키고, 음식 섭취량을 감소시키고, 칼로리 섭취를 감소시키기 위한, 및/또는 예를 들어, 파킨슨병, 알츠하이머병 및 기타 유형의 신경 및 세포 변성의 예방 또는 치료에서 세포보호제로서 사용하기 위한 약제의 제조를 위한, 본 발명의 화합물, 유도체, 염 또는 용매화물의 용도가 본 명세서에 제공된다.
또한, 본 발명의 화합물, 유도체, 염 또는 용매화물의 유효량을 투여하는 단계를 포함하는, 미용 목적을 위해 대상체에서 체중 감소를 유발하거나 체중 증가를 방지하는 방법이 본 명세서에 제공된다.
도 1 내지 도 1bm은 본 발명의 예시 화합물의 아미노산 서열을 나타낸다. 화합물은 표 좌측에서(컬럼 "1"로 표시됨) N-말단 잔기로 제시된다. 각각의 화합물에 대한 아미노산 서열은 2장의 수평 페이지에 걸쳐 제시된다. 공급 및 수용체 결합 실험의 결과는 맨 우측 컬럼에 나타낸다.
서열
본 명세서의 아미노산 서열은 N-말단이 왼쪽에 나타나 있고, 서열이 여러 줄에 걸쳐 제시되어 있는 경우, N-말단은 왼쪽 상단에 있다. 달리 지시되지 않는 한, 서열에서 아미노산 잔기는 L-아미노산이다.
본 출원에 열거된 아미노산 서열은 아미노산에 대한 표준 문자 약어를 사용하여 나타나 있다. 비천연 아미노산 2-아미노아이소부티르산은 그의 통상적인 약어 "AIB"를 갖는다.
본 명세서에 주어진 특정 서열은 본 발명의 특정 실시형태에 관한 것이다.
서열
본 명세서의 아미노산 서열은 N-말단이 왼쪽에 나타나 있고, 서열이 여러 줄에 걸쳐 제시되어 있는 경우, N-말단은 왼쪽 상단에 있다. 달리 지시되지 않는 한, 서열에서 아미노산 잔기는 L-아미노산이다.
본 출원에 열거된 아미노산 서열은 아미노산에 대한 표준 문자 약어를 사용하여 나타나 있다. 비천연 아미노산 2-아미노아이소부티르산은 그의 통상적인 약어 "AIB"를 갖는다.
본 명세서에 주어진 특정 서열은 본 발명의 특정 실시형태에 관한 것이다.
본 발명의 다양한 실시형태의 검토를 용이하게 하기 위해, 하기의 특정 용어 설명이 제공된다:
동물: 예를 들어 포유류 및 조류를 포함하는 카테고리인 살아있는 다세포 척추동물 유기체. 포유류라는 용어는 인간과 비인간 포유류를 모두 포함한다. 유사하게, 용어 "대상체"는 인간 및 수의학 대상체 둘 모두를 포함한다. 본 발명의 바람직한 실시형태에서, 대상체는 인간 대상체이다.
식욕: 음식에 대한 자연스러운 욕구 또는 갈망. 일 실시형태에서, 식욕은 음식에 대한 욕구를 평가하기 위한 설문조사로 측정된다. 식욕 증가는 일반적으로 수유 행동을 증가시킨다.
식욕 억제제: 음식에 대한 욕구를 감소시키는 화합물. 구매가능한 식욕 억제제에는 암페프라몬(다이에틸프로피온), 펜터민, 마진돌 및 페닐프로판올아민 펜플루라민, 덱스펜플루라민 및 플루옥세틴이 포함되나 이에 제한되지 않는다.
체질량 지수(BMI): Quetelet 지수라고도 하는 체질량 측정을 위한 수학식. BMI는 체중(㎏)을 신장2(미터2)로 나눔으로써 계산된다. "정상"으로 받아들여지는 남성과 여성 모두에 대한 현재 표준은 20-24.9 ㎏/m2의 BMI이다. 일 실시형태에서, 25 ㎏/m2 초과의 BMI는 비만 대상체를 식별하는 데 사용할 수 있다. 등급 I 비만(때때로 비만이 아니라 "과체중"이라고 함)은 25 내지 29.9 ㎏/m2의 BMI에 해당한다. 등급 II 비만은 30 내지 40 ㎏/m2의 BMI에 해당하고, 등급 III 비만은 40 ㎏/m2 초과의 BMI에 해당한다(문헌[equier, Am. J Clin. Nutr. 45:1035-47, 1987]. 이상적인 체중은 신장, 체격, 골 구조 및 성별에 따라 종과 개체 간에 달라질 것이다.
심장보호는 심장 세포(특히 심근 세포)를 세포자멸, 괴사 세포 사멸 또는 변성(기능 상실)으로부터 보호하는 것을 지칭한다.
심장보호는 심근 경색 후 가장 자주 요구되지만, 허혈성 심장 질환(예를 들어, 협심증)을 앓고 있는 대상체에게도 사용될 수 있다.
세포보호는 세포를 세포자멸, 괴사 세포 사멸 또는 변성(기능 상실)으로부터 보호하는 것을 지칭한다.
당뇨병: 내인성 인슐린 결핍 및/또는 인슐린 감수성 결함으로 인해 세포가 세포막을 통해 내인성 포도당을 운반하지 못하는 것. 당뇨병은 불충분한 인슐린 분비 또는 표적 조직의 인슐린 저항성으로 인해 탄수화물, 단백질 및 지방 대사가 손상된 만성 증후군이다. 이는, 병인, 병리, 유전학, 발병 연령 및 치료가 상이한, 인슐린 의존성 진성 당뇨병(IDDM, 제I형) 및 인슐린 비의존성 진성 당뇨병(NIDDM, 제II형)의 두 가지 주요 형태로 발생한다.
당뇨병의 두 가지 주요 형태는 둘 다 일정량의 인슐린을 전달하지 못하는 것과 포도당 항상성 제어에 필요한 정확한 타이밍을 특징으로 한다. 제I형 당뇨병 또는 인슐린 의존성 진성 당뇨병(IDDM)은 β 세포의 파괴로 인해 발생하며, 이는 불충분한 내인성 인슐린 수준을 초래한다. 제II형 당뇨병 또는 비인슐린 의존성 당뇨병은 인슐린에 대한 신체의 민감성 결함과 인슐린 생성의 상대적 결핍으로부터 기인한다.
에너지 대사: 신체는 정상적인 대사를 유지하기 위해 일정량의 에너지를 소비해야 한다. 문명인의 경우 종종 매일 약 2,800칼로리로 설정된다. 음식 소비가 이것을 제공하지 않으면 체중 감소가 발생한다. 그러나, 에너지 대사도 조절되며, 예를 들어 글루카곤의 투여는 대사율을 증가시켜 에너지 균형을 달성하고 체중을 유지하기 위해 더 많은 음식 섭취가 필요하다고 생각된다. 따라서 음식 섭취량은 통상의 수준으로 유지되지만 에너지 대사를 높이면 체중이 감소할 것이다.
음식 섭취량: 개체가 소비한 음식의 양. 음식 섭취량은 부피 또는 무게로 측정할 수 있다. 예를 들어, 음식 섭취량은 개체가 소비한 음식의 총량일 수 있다. 섭식 실험에서 '음식 섭취량'은 24시간 동안 동물이 섭취한 표준화된 음식의 무게이다. 또는 음식 섭취량은 개체의 단백질, 지방, 탄수화물, 콜레스테롤, 비타민, 무기질 또는 기타 식품 성분의 양이 될 수 있다. "단백질 섭취량"은 개체가 소비한 단백질의 양을 의미한다. 마찬가지로, "지방 섭취량", "탄수화물 섭취량", "콜레스테롤 섭취량", "비타민 섭취량" 및 "무기질 섭취량"은 개체가 소비한 단백질, 지방, 탄수화물, 콜레스테롤, 비타민 또는 무기질의 양을 의미한다.
GLP-1: 글루카곤 유사 펩티드 1(GLP-1)은 프로글루카곤 유전자의 전사 산물에서 유래한다. GLP-1의 생물학적 활성 형태는 GLP-1(7-37) 및 GLP-1(7-36)-NH2로 알려진 절단 형태이다(-NH2 지정은 C-말단 아미노산이 카르복실산 기 대신 -C(O)NH2 기를 갖는 아미노산 서열을 나타냄).
인간 GLP-1(7-37)의 서열은 His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-lle-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly이다. [서열 번호 529]
인간 GLP-1(7-36)-NH2의 서열은 His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-lle-Ala-Trp-Leu-Val-Lys-Gly-Arg- CONH2이다. [서열 번호 530]
글루카곤: 글루카곤은 프로글루카곤 유전자에서 유래된 펩티드이다. 이것은 인간의 29-아미노산 폴리펩티드이며 하기 서열을 갖는다:
His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr. [서열 번호 531]
신경보호는 신경계(바람직하게는 중추신경계) 내의 뉴런을 세포자멸, 괴사성 세포 사멸 또는 변성(기능 상실)으로부터 보호하는 것을 지칭한다. 본 발명의 다양한 양태와 관련된 것을 포함하는 신경보호 치료는 뇌 손상(예를 들어 뇌졸중, 뇌종양, 감염, 중독, 저산소증, 허혈, 뇌병증 또는 약물 남용과 같은 신체적 외상 또는 비외상적 손상 이후의 것) 후에 요구될 수 있다. 본 발명의 다양한 양태와 관련된 것을 포함하는 신경보호 치료는 또한 알츠하이머병, 파킨슨병, 게릭병 또는 헌팅턴병과 같은 만성 신경퇴행성 질환을 갖는 대상체에서 지시될 수 있다.
정상적인 일일 식단: 주어진 종의 개체에 대한 평균 음식 섭취량. 정상적인 일일 식단은 칼로리 섭취량, 단백질 섭취량, 탄수화물 섭취량 및/또는 지방 섭취량으로 표현될 수 있다. 인간의 정상적인 일일 식단은 일반적으로 다음을 포함한다: 약 2,000, 약 2,400 또는 약 2,800 내지 훨씬 더 많은 칼로리. 또한, 인간의 정상적인 일일 식단은 일반적으로 약 12g 내지 약 45g의 단백질, 약 120g 내지 약 610g의 탄수화물 및 약 11g 내지 약 90g의 지방을 포함한다. 저칼로리 식단은 개체의 정상 칼로리 섭취량의 약 85% 이하, 바람직하게는 약 70% 이하가 될 것이다.
동물의 경우, 칼로리 및 영양소 요구량은 동물의 종과 크기에 따라 달라진다. 예를 들어, 고양이의 경우 파운드당 총 칼로리 섭취량과 단백질, 탄수화물 및 지방의 백분율 분포는 고양이의 연령 및 번식 상태에 따라 달라진다. 그러나 고양이를 위한 일반적인 지침은 40 cal/lb/일(18.2 cal/㎏/일)이다. 약 30% 내지 약 40%는 단백질, 약 7% 내지 약 10%는 탄수화물, 약 50% 내지 약 62.5%는 지방 섭취에서 유래되어야 한다. 당업자는 임의의 종 개체의 정상적인 일일 식이를 쉽게 확인할 수 있다.
비만: 과도한 체지방이 사람을 건강 위험에 빠뜨릴 수 있는 상태(문헌[Barlow and Dietz, Pediatrics 102:E29, 1998; National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI), Obes. Res. 6 (suppl. 2):51 S-209S, 1998]을 참조). 과도한 체지방은 에너지 섭취와 에너지 소비의 불균형의 결과이다. 예를 들어 체질량 지수(BMI)는 비만을 평가하는 데 사용될 수 있다. 일반적으로 사용되는 하나의 관례에서, BMI 25.0 내지 29.9 ㎏/m2는 과체중이고 BMI 30 ㎏/m2 이상은 비만이다.
다른 관례에서, 허리 둘레가 비만을 평가하는 데 사용된다. 이 관례에서, 남성의 경우 허리 둘레가 102 cm 이상, 여성의 경우 허리 둘레가 89 cm 이상이면 비만으로 간주된다. 비만이 개체의 이환율과 사망률 모두에 영향을 미친다는 강력한 증거가 있다. 예를 들어, 비만 개체는 특히 심장 질환, 인슐린 비의존성(제2형) 당뇨병, 고혈압, 뇌졸중, 암(예를 들어, 자궁내막암, 유방암, 전립선암, 결장암), 이상지질혈증, 담낭 질환, 수면 무호흡증, 출산율 감소, 및 골관절염에 대한 위험이 증가한다(문헌[Lyznicki et al., Am. Fam. Phys. 63:2185, 2001] 참조).
과체중: 이상적인 체중보다 체중이 더 나가는 개체. 과체중 개체는 비만일 수 있지만 반드시 비만인 것은 아니다. 예를 들어, 과체중 개체는 그의 체중을 줄이려는 임의의 개체이다. 하나의 관례에서, 과체중 개체는 BMI가 25.0 ㎏/m2 내지 29.9 ㎏/m2인 개체이다.
옥신토모둘린(OXM): 옥신토모둘린은 글루카곤의 전체 29개 아미노산 서열을 포함하는 글루카곤 수퍼패밀리의 37개 아미노산 펩티드 구성원이며, 뇌와 장에서 프리-프로-글루카곤 전구체의 조직 특이적 처리로 인해 8개 아미노산 카르복시 말단 확장이 있다. 인간 OXM 서열은 다음과 같다:
His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-Lys-Arg-Asn-Arg-Asn-Asn-lle-Ala. [서열 번호 532]
PEG화 및 PEG화된: PEG화는 폴리(알킬렌 글리콜), 바람직하게는 활성화된 폴리(알킬렌 글리콜)을 반응시켜 공유 결합을 형성하는 과정을 지칭한다. 촉진제, 예를 들어 아미노산, 예를 들어 라이신이 사용될 수 있다. "PEG화"는 종종 폴리(에틸렌 글리콜) 또는 메톡시 폴리(에틸렌 글리콜)과 같은 이의 유도체를 사용하여 수행되지만, 이 용어는 본 명세서에서 메톡시 폴리(에틸렌 글리콜)의 사용에 제한되지 않고 임의의 다른 유용한 폴리(알킬렌 글리콜), 예를 들어 폴리(프로필렌 글리콜)의 사용을 포함한다. 용어 PEG화된은 이러한 폴리(알킬렌 글리콜) 기를 함유하는 화합물을 지칭한다.
pl: pl은 등전점의 약어이다. 때때로 사용되는 대안적인 약어는 IEP이다. 이는 특정 분자가 순 전하를 갖지 않는 pH이다. pl보다 낮은 pH에서 단백질 또는 펩티드는 순 양전하를 갖는다. pl보다 높은 pH에서 단백질 또는 펩티드는 순 음전하를 갖는다. 단백질과 펩티드는 폴리아크릴아미드 겔에 포함된 pH 구배를 이용하는 전기 영동 방법인 등전 포커싱이라는 기술을 사용하여 등전점에 따라 분리될 수 있다.
말초 투여: 중추신경계 외부 투여.
말초 투여는 뇌에 대한 직접적인 투여를 포함하지 않는다. 말초 투여는 혈관내, 근육내, 피하, 흡입, 경구, 직장, 경피 또는 비강내 투여를 포함하지만 이에 제한되지 않는다.
폴리펩티드: 단량체가 아미드 결합을 통해 함께 연결된 아미노산 잔기인 중합체. 문맥상 달리 지시되지 않는 한, 본 명세서에서 사용되는 용어 "폴리펩티드", "펩티드" 또는 "단백질"은 임의의 아미노산 서열을 포함하고 당단백질과 같은 변형된 서열을 포함한다. 용어 "폴리펩티드"는 자연적으로 발생하는 단백질뿐만 아니라 재조합 또는 합성으로 생산되는 단백질을 포함한다. 용어 "폴리펩티드 단편"은 폴리펩티드의 일부, 예를 들어 수용체 결합에 있어서 적어도 하나의 유용한 서열을 나타내는 단편을 의미한다. 용어 "폴리펩티드의 기능적 단편"은 폴리펩티드의 활성을 유지하는 폴리펩티드의 모든 단편을 지칭한다. 생물학적 기능성 펩티드는, 관심 펩티드가 원하는 활성을 감소시키지 않는 다른 펩티드에 융합된, 융합 단백질을 포함할 수 있다.
피하 투여: 피하 투여는 피부 진피와 하부 조직 사이에서 발견되는 피하 지방층에 물질을 투여하는 것이다. 피하 투여는 예를 들어 주사기 또는 "펜" 유형 주사 장치에 맞춰진 피하 주사바늘을 사용한 주사에 의한 것일 수 있다. 예를 들어 마이크로니들과 같은 다른 투여 방법이 사용될 수 있다. 피하 주사바늘을 사용한 주사는 일반적으로 수용체를 대신하여 어느 정도의 통증을 수반한다. 이러한 통증은 국소 마취제 또는 진통제를 사용하여 가려질 수 있다. 그러나, 주사의 지각된 통증을 감소시키는데 사용되는 통상적인 방법은 주사 직전에 및 주사 동안 대상체의 주의를 분산시키는 것이다. 상대적으로 작은 게이지의 피하 주사바늘을 사용하고, 상대적으로 적은 양의 물질을 주입하고, 대상체가 주사 부위에서 "따끔거리는" 느낌을 받을 수 있는 과도한 산성 또는 알칼리성 조성물을 피함으로써 통증을 최소화할 수 있다. pH 4와 pH 10 사이의 pH를 갖는 조성물은 일반적으로 견딜 수 있을 정도로 편안한 것으로 간주된다.
치료적 유효량: 진행을 방지하거나 장애의 퇴행을 유발하거나 장애의 징후 또는 증상을 완화할 수 있거나 원하는 결과를 달성할 수 있는 충분한 용량. 일부 실시형태에서, 본 발명의 화합물의 치료적 유효량은 체중 증가를 억제하거나 중단시키기에 충분한 양, 또는 식욕을 감소시키기에 충분한 양이다.
본 발명의 화합물
본 발명자들은 본 발명의 예시 화합물이 생체내에서 체중 손실을 야기하는 것을 포함하는 특성을 갖는다는 것을 알아내었다. 화합물은 또한 혈액에서 긴 반감기를 가지는데, 이는 이들이 편리하게 낮은 빈도로 투여될 수 있음을 의미한다. 이러한 측면에서, 본 발명의 화합물은 공지된 화합물 세마글루티드와 비교하여 개선된 프로파일을 갖는다.
전술한 GLP-1 및 GLP-1의 유도체와 비교하여, 본 발명의 화합물은 위치 42에 라이신 잔기가 존재하고 그 라이신 잔기가 특정 방식으로 기능화되어 기 R-R1(여기서 R1은 CO2H임)을 포함하는 것을 포함하는, 특정 잔기로 C-말단에서 연장된다. 이들은 이전에 조사되지 않았던 기능화이며, 본 발명자들에 의해 발견된 유익한 특성은 이전에 본 적이 없다.
전술한 바와 같이, 본 발명의 화합물은 하기 식 (I)을 갖는다:
Xaa1 - AIB2- Xaa3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Xaa10-Ser11 - Lys12- Gln 13-Leu14- Glu15- Glu16-Xaa17-Xaa18-Val19-Xaa20-Xaa21 -Phe22- Ile23- Glu24-Trp25-Leu26- Lys27-Xaa28-Xaa29-Gly30-Pro31 -Ser32-Xaa33-Gly34-Xaa35-Xaa36- Pro37-Pro38-Xaa39-Xaa40-Xaa41 -Lys42; (I) [서열 번호 528]
상기 식에서,
Xaa1은 His, Tyr 또는 Phe이고;
Xaa3은 His, Gln 또는 Glu이고;
Xaa10은 Leu, Tyr 또는 Val이고;
Xaa17은 Glu 또는 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg, Gln, Lys 또는 His이고;
Xaa21은 Leu, Ala, Arg, Lys 또는 Glu이고;
Xaa28은 Ala, Asn, Gln 또는 His이고;
Xaa29는 Gly 또는 Ala이고;
Xaa33은 Ser, His 또는 Gln이고;
Xaa35는 Lys, Pro, His, Arg, Asn, Gln, Glu, Ser 또는 Ala이고;
Xaa36은 Phe, His, Gln, Glu, Lys, Ser, Arg이거나 부재하고;
Xaa39는 Pro 또는 Gly이고;
Xaa40은 Gly이거나 부재하고;
Xaa41은 Lys이거나 또는 부재하고;
위치 42에서의 라이신 잔기는 그의 ε-아미노기에서 기 Y로 치환되고, Y는
Z-Xaa43-Xaa44-이고, 여기서,
Xaa43은 Asn이거나 부재하고;
Xaa44는 His이거나 부재하고;
Z는 하기 화학식의 기이다:
(여기서, R은 Ci6-Ci8 알킬렌 또는 알케닐렌 기이고;
R1은 CO2H임).
분자의 제1 부분(Xaa1-Lys42) 내에서, 하기가 바람직하다:
Xaa17은 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Leu 또는 Glu이고;
Xaa28은 Ala, Gln 또는 His이고;
Xaa29는 Gly이고;
Xaa33은 Ser이고;
Xaa35는 Lys, Glu, His, Gln 또는 Asn이고;
Xaa36은 부재하고;
Xaa39는 Pro이고;
Xaa41은 Lys이다.
더 바람직한 실시형태에서, 분자의 제1 부분(Xaa1-Lys42)에서,
Xaa1은 His 또는 Phe이고;
Xaa3은 His 또는 Glu이고;
Xaa10은 Tyr 또는 Val이고;
Xaa17은 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Glu이고;
Xaa28은 Ala 또는 Gln이고;
Xaa29는 Gly이고;
Xaa33은 Ser이고;
Xaa35은 Lys이고;
Xaa36은 부재하고;
Xaa39는 Pro이고;
Xaa40은 Gly이고;
Xaa41은 Lys이다.
결과적으로 잔기를 고려하면, Xaa1은 His, Tyr 및 Phe로부터 선택된다. 예를 들어, Xaa1은 His 및 Tyr로부터 선택되거나, 또는 대안적으로 Xaa1은 His 및 Phe로부터 선택된다. 예를 들어, Xaa1은 His이다. 대안적으로, Xaa1은 Phe이다. 특히 바람직한 실시형태에서, Xaa1은 Phe이다. N-말단에 Phe를 갖는 본 발명의 화합물(특히 Xaa3 = Glu를 갖는 것)은 GLP-1 수용체 편향을 갖는 것으로 밝혀졌다. N-말단에 Phe를 갖는 화합물은 천연 GLP1과 유사한 방식으로 세포내 cAMP 시스템을 완전히 활성화하는 반면, 세포내 베타 아레스틴 메신저 시스템을 활성화하는 데는 GLP1보다 약하므로 GLP1 수용체에 편향이 존재한다. 일부 상황에서, 이러한 GLP1 수용체 편향은 GLP1 수용체에서의 작용을 연장시키고 음식 섭취 억제 및 음식 혐오와 같은 다른 용량 제한 효과를 증가시키지 않으면서 인슐린을 방출하는 베타 세포에 대한 작용을 상대적으로 향상시키는 이점이 있다.
Xaa3은 His, Gln 및 Glu로부터 선택된다. 바람직하게는, Xaa3은 His 및 Glu로부터 선택된다. 예를 들어, Xaa3은 His이다. 대안적으로, Xaa3은 Glu이다. 특히 바람직한 실시형태에서, Xaa3은 Glu이다.
Xaa10은 Leu, Tyr 및 Val로부터 선택된다. 바람직하게는, Xaa10은 Tyr 또는 Val이고, 예를 들어 Xaa10은 Tyr이다. 대안적으로, Xaa10은 Val이다.
Xaa17은 Glu 또는 Lys로부터 선택된다. 바람직하게는, Xaa17은 Lys이다.
Xaa18은 Ala 또는 Arg로부터 선택된다. 예를 들어, Xaa18은 Ala이다. 대안적으로, Xaa18은 Arg이다. 특히 바람직한 실시형태에서, Xaa18은 Arg이다.
Xaa20은 Arg, Gln, Lys 및 His로부터 선택된다. 바람직하게는, Xaa20은 Arg 또는 His이고, 예를 들어 Xaa20은 Arg이다. 대안적으로, Xaa20은 His이다. 특히 바람직한 실시형태에서, Xaa20은 Arg이다.
Xaa21은 Leu, Ala, Arg, Lys 및 Glu로부터 선택된다. 바람직하게는, Xaa21은 Leu 또는 Glu이고, 예를 들어, Xaa21은 Glu이다. 대안적으로, Xaa21은 Leu이다. 특히 바람직한 실시형태에서, Xaa21은 Glu이다.
Xaa28은 Ala, Asn, Gln 및 His로부터 선택된다. 바람직하게는, Xaa28은 Ala, Gln 및 His로부터 선택된다. 특히 바람직한 실시형태에서, Xaa28은 Ala 또는 Gln이고, 예를 들어 Xaa28은 Ala이다. 대안적으로, Xaa28은 Gln이다.
Xaa29는 Gly 및 Ala로부터 선택된다. 바람직하게는, Xaa29는 Gly이다.
Xaa33은 Ser, His 및 Gln으로부터 선택된다. 예를 들어, Xaa33은 Ser 및 His로부터 선택되거나, 또는 대안적으로 Xaa33은 Ser 및 Gln으로부터 선택된다. 바람직하게는, Xaa33은 Ser이다.
Xaa35는 Lys, Pro, His, Arg, Asn, Gln, Glu, Ser 및 Ala로부터 선택된다. 바람직하게는, Xaa35는 Lys, Gln, Glu, His 및 Asn으로부터 선택된다. 특히 바람직한 실시형태에서, Xaa35는 Lys이다.
Xaa36은 Phe, His, Gln, Glu, Lys, Ser, Arg이거나 또는 Xaa36은 부재한다.
바람직하게는, Xaa36은 부재한다.
Xaa39는 Pro 또는 Gly로부터 선택된다. 바람직하게는, Xaa39는 Pro이다.
Xaa40은 Gly이거나 또는 Xaa40은 부재한다. 바람직하게는, Xaa40는 Gly이다.
Xaa41은 Lys이거나 또는 Xaa41은 부재한다. 바람직하게는, Xaa41은 Lys이다.
바람직한 실시형태에서, Xaa36은 부재하고, Xaa37-Xaa41은 Pro37-Pro38-Pro39-Gly40-Lys41 [서열 번호 533]이고, 대안적인 바람직한 실시형태에서, Xaa36은 부재하고, Xaa40은 부재하고, Xaa37-Xaa41은 Pro37-Pro38-Pro39-Lys41 [서열 번호 534]이다.
기 Y
본 발명의 화합물에서, Lys42 상의 ε-아미노기는 분자의 Y 부분의 Xaa44 잔기의 산기에 부착되어 결합은 아미드 결합이다. Xaa44 또는 Xaa43이 부재하는 경우, Lys42 상의 ε-아미노기는 존재하는 다음 잔기의 산 기에 부착된다: Z 기의 산 기.
라이신 잔기에서, ε-아미노기는 6-탄소에 부착된 아미노기이다. 표준 IUPAC 명명법에 따라 라이신의 원자는 다음과 같이 번호가 매겨져, 탄소 원자 넘버링 및 α 내지 ε 위치를 나타낸다:
본 명세서에서 지칭되는 Lys42 상의 ε-아미노기는 표시된 바와 같이 C-6 탄소 원자 상의 아미노기이다.
분자의 Y 부분 내에서,
Xaa43은 Asn이거나 부재할 수 있고;
Xaa44는 His이거나 부재할 수 있다.
예를 들어, Xaa43은 Asn이고 Xaa44는 His이거나; 또는 Xaa43은 Asn이고 Xaa44는 부재하거나; 또는 Xaa43은 부재하고 Xaa44는 His이거나; 또는 Xaa43 및 Xaa44 둘 모두는 부재한다. 바람직한 실시형태에서, Xaa43은 부재하고 Xaa44는 부재한다.
예를 들어, Y는
Z-Asn-His-;
Z-Asn-;
Z-His-; 또는
Z-이다.
기 Z
분자의 Z 부분 내에서, 기 R은, 아미노 결합을 통해 Glu 잔기에 의해 한쪽 끝에서 잔기 Xaa43(또는 Xaa43이 부재하는 경우 Xaa44이거나, Xaa43 및 Xaa44 둘 모두가 부재하는 경우, Lys42임)에 연결된, 알킬렌 또는 알케닐렌 사슬이다. 다른 쪽 끝에서 R 알킬렌 또는 알케닐렌 사슬은 R1 산 기(CO2H)에 연결된다.
일반적으로, R은 짝수 개의 탄소 원자를 갖는다. 예를 들어, R은 자연 발생 지방산에서 발견되는 알킬렌 또는 알케닐렌 사슬일 수 있다. 뿌리 지방산은 R 알킬렌 또는 알케닐렌 사슬의 탄소 원자 수보다 2배 더 긴 사슬 길이를 갖는다.
R은 C16-C18 알킬렌 또는 알케닐렌 기이다. 예를 들어, R은 직쇄 알킬렌 또는 알케닐렌 기이다. 예를 들어, R은 C16 또는 C18 직쇄 알킬렌 기이다. 예를 들어, R이 C16 기인 경우, 옥타데칸디오산 모이어티에 의해 제공될 수 있다. 예를 들어, R이 C18 기인 경우, 에이코산디오산 모이어티에 의해 제공될 수 있다.
바람직한 실시형태에서, R은 C18 알킬렌 기이다.
일 실시형태에서, 하기가 바람직하다:
Xaa17은 Lys이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Leu 또는 Glu이고;
Xaa28은 Ala, Gln 또는 His이고;
Xaa29는 Gly이고;
Xaa33은 Ser이고;
Xaa35는 Lys, Glu, His, Gln 또는 Asn이고;
Xaa36은 부재하고;
Xaa39는 Pro이고;
Xaa41은 Lys이고;
Xaa43은 부재하고;
Xaa44는 부재하고;
R은 C18 알킬렌 기이다.
더 바람직한 실시형태에서,
Xaa1은 His 또는 Phe이고;
Xaa3은 His 또는 Glu이고;
Xaa10은 Tyr 또는 Val이고;
Xaa17은 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Glu이고;
Xaa28은 Ala 또는 Gln이고;
Xaa35는 Lys이고;
Xaa40은 Gly이다.
예를 들어, 이러한 실시형태에서,
Xaa1은 Phe이고;
Xaa3은 Glu이고;
Xaa10은 Val이고;
Xaa18은 Arg이고;
Xaa20은 Arg이고;
Xaa28은 Gln이다.
예를 들어, 이러한 화합물은 서열 번호 502의 화합물일 수 있다.
특히 바람직한 실시형태에서, 화합물은 도 1 내지 도 1bm의 표에 제시된 본 발명의 화합물 중 하나이다.
유도체 및 염
본 발명은 식 (I)의 화합물, 이러한 화합물의 유도체, 및 이러한 화합물 및 유도체의 염 또는 용매화물을 제공한다.
화합물, 유도체 및 염은 당업계에 잘 알려진 재조합 방법에 의해 제조될 수 있거나, 또는 대안적으로 이들은 또 당업계에 잘 알려진 합성 방법에 의해 제조될 수 있다.
유도체
일부 실시형태에서, 본 발명은 식 (I)의 화합물에 관한 것이지만, 유도체가 아니며, 다른 실시형태에서 본 발명은 식 (I)의 화합물의 유도체에 관한 것이다. 유도체는 예를 들어 아미드화, 글리코실화, 카르바밀화, 아실화, 황산화, 인산화, 고리화, 지질화, 페길화, 및 융합 단백질을 형성하기 위한 또 다른 펩티드 또는 단백질에 대한 융합으로부터 선택되는 하나 이상의 유도체화를 포함할 수 있고, 예를 들어 유도체는 아미드화, 글리코실화, 카르바밀화, 아실화, 황산화, 인산화, 고리화, 지질화 및 페길화로부터 선택되는 하나 이상의 유도체화를 포함할 수 있다. 구조는 분자 내의 무작위 위치에서 또는 분자 내의 미리 결정된 위치에서 변형될 수 있으며 1개, 2개, 3개 또는 그 이상의 부착된 화학적 모이어티를 포함할 수 있다.
특정 실시형태에서, 본 발명의 화합물의 1차 펩티드 사슬이 그의 C-말단에서 아미드화될 수 있는 것이 바람직하다. 이러한 변형은 C-말단에서 아미드화되기 쉬운, 특정 위장관 펩티드 호르몬을 포함하여 자연 발생 펩티드의 대략 절반으로 자연에서 매우 흔하다. 본 발명은 아미드화 및 비아미드화 형태 둘 모두의 서열 목록 및 도면을 포함하는 본 명세서에 개시된 모든 일반적인 및 특정 서열을 포괄하며, 아미드화는 특히 1차 펩티드 서열의 C-말단 상에 존재하는 것이 바람직하다.
유도체는 예를 들어 융합 단백질일 수 있으며, 여기서 식 (I)의 구조는 당업계에 공지된 재조합 방법을 사용하여 또 다른 단백질 또는 폴리펩티드(융합 파트너)에 융합된다. 대안적으로, 이러한 융합 단백질은 임의의 공지된 방법에 의해 합성될 수 있다. 이러한 융합 단백질은 식 (I)의 구조를 포함한다. 임의의 적합한 펩티드 또는 단백질이 융합 파트너(예를 들어, 혈청 알부민, 탄산무수화효소, 글루타티온-S-전이효소 또는 티오레독신 등)로서 사용될 수 있다. 이러한 융합 단백질은 융합 파트너의 카르복시-말단을 식 (I)의 구조의 아미노-말단에 연결하거나 그 반대로 연결함으로써 만들어질 수 있다. 선택적으로, 절단가능한 링커는 융합 파트너에 식 (I)의 구조를 연결하기 위해 사용될 수 있다. 생성된 절단가능한 융합 단백질은 본 발명의 화합물의 활성 형태가 방출되도록 생체내에서 절단될 수 있다. 이러한 절단가능한 링커의 예는 링커 Asp-Asp-Asp-Asp-Tyr [서열 번호 535], Gly-Pro-Arg, Ala-Gly-Gly 및 His-Pro-Phe-His-Leu [서열 번호 536]를 포함하지만 이에 제한되지 않으며, 이는 각각 엔테로키나제, 트롬빈, 유비퀴틴 절단 효소 및 레닌에 의해 절단될 수 있다. 세부 내용은 예를 들어 미국 특허 제6,410,707호를 참조하며, 상기 문헌의 내용은 본 명세서에 참조로 포함된다.
본 발명의 유도체는 예를 들어 식 (I)의 구조의 생리학적 기능성 유도체일 수 있다. 용어 "생리학적 기능성 유도체"는 상응하는 변형되지 않은 화합물과 동일한 생리학적 기능을 갖는 식 (I)의 화합물의 화학적 유도체를 나타내기 위해 본 명세서에서 사용된다. 예를 들어, 생리학적 기능성 유도체는 체내에서 식 (I)의 화합물로 전환될 수 있다. 본 발명에 따른 생리학적 기능성 유도체의 예로는 에스테르, 아미드 및 카르바메이트; 바람직하게는 에스테르 및 아미드를 포함한다.
Lys42에서의 유도체에 더하여, 본 발명의 화합물은 추가 위치에서 추가로 유도체화될 수 있다. 예를 들어, 본 발명의 화합물의 약제학적으로 허용가능한 에스테르 및 아미드는, 예를 들어 알코올 또는 아미노 모이어티를 함유하는 알킬, 알케닐 아릴, 아르알킬 또는 아미노 알킬 기와 식 (I)의 화합물에 존재하는 산 모이어티의 반응에 의해 형성된, 또는 활성화된 아실 기를 함유하는 알킬, 알케닐 아릴, 아르알킬 또는 아미노 알킬 기와 식 (I)의 화합물에 존재하는 알코올 또는 아민 기의 반응에 의해 형성된, 적절한 부위에 부착된 C1-20 알킬-, C2-20 알케닐-, C5-10 아릴-, C5-10 아르-C1-20 알킬-, 또는 아미노산- 에스테르 기 또는 아미드 기를 포함할 수 있다. 적합한 모이어티의 예는 4 내지 26개의 탄소 원자, 바람직하게는 5 내지 19개의 탄소 원자를 갖는 소수성 치환체이다. 적합한 지질 기는 지방산(예를 들어, 라우로일(C12H23), 팔미틸(C15H31), 올레일(C15H29) 또는 스테아릴(C17H35)) 및 담즙산(예를 들어, 콜레이트 또는 데옥시콜레이트)을 포함한다.
지방산 유도체로 설프하이드릴-함유 화합물을 지질화하는 방법은 미국 특허 제5,936,092호; 미국 특허 제6,093,692호; 및 미국 특허 제6,225,445호에 개시되어 있으며, 이의 내용은 본 명세서에 참고로 포함된다. 이황화 결합을 통해 지방산에 연결된 본 발명의 화합물을 포함하는 본 발명의 화합물의 지방산 유도체는 신경 세포 및 조직으로의 본 발명의 화합물의 전달에 사용될 수 있다. 지질화는 상응하는 지질화되지 않은 화합물의 흡수 속도에 비해 화합물의 흡수를 현저하게 증가시킬 뿐만 아니라 화합물의 혈액 및 조직 유지를 연장시킨다.
더욱이, 지질화된 유도체의 이황화 결합은 세포에서 상대적으로 불안정하며, 지방산 모이어티로부터 분자의 세포내 방출을 촉진한다.
적합한 지질-함유 모이어티는 4 내지 26개의 탄소 원자, 바람직하게는 5 내지 19개의 탄소 원자를 갖는 소수성 치환체이다. 적합한 지질 기는 지방산(예를 들어, 라우로일(C12H23), 팔미틸(C15H31), 올레일(C15H29) 또는 스테아릴(C17H35)) 및 담즙산(예를 들어, 콜레이트 또는 데옥시콜레이트)을 포함한다. 본 발명의 지질 기능화 화합물은 특정 상황에서 이점을 가질 수 있지만, 대부분의 경우, 추가 지질 기가 존재하지 않도록 본 발명의 화합물이 추가로 유도체화되지 않는 것이 가장 간단하고 바람직할 것으로 예상된다.
고리화 방법으로는 이황화 가교 형성을 통한 고리화 및 고리화 수지를 이용한 헤드-투-테일 고리화를 포함한다. 고리화된 펩티드는 구조적 제약으로 인해 효소 분해에 대한 저항성 증가를 포함하여 향상된 안정성을 가질 수 있다. 고리화는 고리화되지 않은 펩티드가 N-말단 시스테인 기를 포함하는 경우에 특히 편리할 수 있다. 적합한 고리화된 펩티드는 단량체 및 이량체성 헤드-투-테일 고리화 구조를 포함한다. 고리화된 펩티드는 하나 이상의 추가 잔기, 특히 이황화 결합 형성을 위해 포함된 추가 시스테인 또는 수지 기반 고리화를 위해 포함된 측쇄를 포함할 수 있다.
유도체는 예를 들어 식 (I)의 PEG화된 구조일 수 있다. 본 발명의 PEG화된 화합물인 유도체는 폴리펩티드의 증가된 용해도, 안정성 및 순환 시간 또는 감소된 면역원성과 같은 추가적인 이점을 제공할 수 있다(미국 특허 제4,179,337호를 참조하며, 이의 내용은 본 명세서에 참조로 포함된다).
본 발명의 화합물의 유도체화를 위한 화학적 모이어티는 또한 폴리에틸렌 글리콜, 에틸렌 글리콜/프로필렌 글리콜 공중합체, 카르복시메틸셀룰로오스, 덱스트란, 폴리비닐 알코올 등과 같은 수용성 중합체로부터 선택될 수 있다. 본 발명의 화합물의 유도체화를 위한 중합체 모이어티는 임의의 분자량의 것일 수 있고 분지형 또는 비분지형일 수 있다. 용이한 취급 및 제조를 위해, 본 발명의 화합물의 유도체화를 위한 폴리에틸렌 글리콜의 바람직한 분자량은 약 1 kDa 내지 약 100 kDa이며, 용어 "약"은 폴리에틸렌 글리콜의 제조에서 일부 분자가 명시된 분자량보다 많거나 적을 수 있음을 나타낸다. 원하는 치료 프로파일, 예를 들어 원하는 지속 방출 기간, 생물학적 활성에 미치는 영향(있는 경우), 취급 용이성, 항원성의 정도 또는 결여, 및 치료용 단백질 또는 유사체에 대한 폴리에틸렌 글리콜의 기타 알려진 영향에 따라 다른 분자량의 중합체가 사용될 수 있다. 예를 들어, 폴리에틸렌 글리콜은 약 200, 500, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10,000, 10,500, 11,000, 11,500, 12,000, 12,500, 13,000, 13,500, 14,000, 14,500, 15,000, 15,500, 16,000, 16,500, 17,000, 17,500, 18,000, 18,500, 19,000, 19,500, 20,000, 25,000, 30,000, 35,000, 40,000, 45,000, 50,000, 55,000, 60,000, 65,000, 70,000, 75,000, 80,000, 85,000, 90,000, 95,000, 또는 100,000 kDa의 평균 분자량을 가질 수 있다.
염
식 (I)의 화합물 및 이러한 화합물의 유도체의 염 형태는 또한 본 발명의 일부를 형성한다. 일부 실시형태에서, 염은 식 (I)의 화합물의 염이다. 다른 실시형태에서, 염은 식 (I)의 화합물의 유도체의 염이다.
본 발명의 화합물의 염은 약제학적으로 허용가능한, 즉 의약에 사용하기에 적합한 것들을 포함한다. 그러나, 예를 들어 화합물의 제조에서 중간체로서 사용하기 위한 약제학적으로 허용가능하지 않은 반대 이온을 갖는 염도 또한 본 발명의 범주 내에 있다.
본 발명에 따른 적합한 염은 유기 또는 무기 산 또는 염기로 형성된 염을 포함한다. 약제학적으로 허용가능한 산 부가 염은 염산, 브롬화수소산, 황산, 질산, 시트르산, 타르타르산, 아세트산, 인산, 락트산, 피루브산, 아세트산, 트라이플루오로아세트산, 석신산, 과염소산, 푸마르산, 말레산, 글리콜산, 살리실산, 옥살로아세트산, 메탄술폰산, 에탄술폰산, p-톨루엔술폰산, 포름산, 벤조산, 말론산, 나프탈렌-2-술폰산, 벤젠술폰산 및 이세티온산으로부터 형성된 것들을 포함한다. 옥살산과 같은 다른 산은 최종 형태로 본 발명의 화합물을 얻는 데 있어서 중간체로서 유용할 수 있다.
염기와의 약제학적으로 허용가능한 염은 암모늄 염, 알칼리 금속 염, 예를 들어 칼륨 및 나트륨 염, 알칼리 토금속 염, 예를 들어 칼슘 및 마그네슘 염, 및 유기 염기와의 염, 예를 들어 다이사이클로헥실아민 및 N-메틸-D-글루코민을 포함한다.
용매화물
유기 및/또는 의약 화학의 당업자는, 많은 유기 화합물이 이들이 반응하거나, 또는 이들이 침전되거나 결정화되는 용매와 복합체를 형성할 수 있음을 인식할 것이다. 이러한 착물은 "용매화물"로 알려져 있다. 예를 들어, 물과의 착물은 "수화물"로 알려져 있다. 본 발명은 또한 식 (I)의 화합물의 용매화물, 화합물의 유도체의 용매화물, 및 유도체의 염의 용매화물을 포함한다.
유기 및/또는 의약 화학의 분야의 숙련자는 또한 많은 유기 화합물이 무정형 재료로서 그리고/또는 하나 이상의 결정형을 비롯한 상이한 형태로 존재할 수 있음을 이해할 것이다. 유기 화합물의 상이한 물리적 형태는 다형체로서 알려져 있다. 본 발명은 또한 식 (I)의 화합물의 모든 이러한 상이한 물리적 형태뿐만 아니라 이들의 유도체 및 염의 상이한 물리적 형태를 포함한다.
생물학적 활성
본 발명의 화합물은 인간 GLP-1 수용체에서 활성을 갖고 GLP-1 수용체 작용제로 간주될 수 있다. 이는 예를 들어 시험관내 또는 세포 결합 검정 또는 리포터 검정에 의해 평가될 수 있다. 본 발명의 바람직한 화합물은 예를 들어, 하기 실시예 섹션에 기재된 검정에 따라 시험된 경우, 인간 GLP-1의 활성의 적어도 1/50인 인간 GLP-1 수용체에서의 활성, 바람직하게는 인간 GLP-1의 활성의 적어도 1/30, 1/20, 1/10, 1/3 또는 1/2인 활성을 나타낸다.
GLP-1 수용체에서의 활성을 평가하는 방법은 잘 알려져 있다. 예를 들어, 문헌[Jones et al., Nat. Commun., 2018, 9(1), 1602]에는 GLP-1 수용체 결합을 검정하는 방법이 개시되어 있다. 구체적 방법이 하기에 기재된다.
본 발명의 바람직한 화합물은 인슐린 방출/분비 촉진에 효과적이다. 이는 예를 들어 시험관내 분석에 의해 평가될 수 있다. 베타-세포로부터 인슐린의 방출을 평가하는 방법은 잘 알려져 있다.
본 발명의 화합물은 하기 기준의 일부, 또는 더 바람직하게는 전부를 충족시킨다:
1) 식욕을 억제하는 인간 GLP-1 수용체에서의 지속적인 생체활성;
2) 베타 세포로부터 인슐린 방출을 촉진하는 활성;
3) 저용량 주사(그럼으로써 주사 통증을 낮춤)로 유효 용량을 투여할 수 있게 하는 pH 4.5의 수용액에서의 높은 용해도. 용해도는 간단한 시험관 내 시험으로 쉽게 평가할 수 있음;
4) 여전히 허용가능한 치료적 또는 미용적 이점을 생성하면서 매일, 바람직하게는 2회 이하, 또는 더 바람직하게는 1주에 1회 이하의 주사를 허용하도록 하는 (인간 또는 동물 모델에서 평가된 바와 같은) 장기간의 생체내 활성;
5) 양호한 체중 손실(인간 대상체 또는 동물 모델에서 평가된 바와 같음);
6) 인간에서 낮은 항원성. 이는 인간 또는 동물 모델(특히 인간 항체 레퍼토리를 모방하기 위해 인간 면역 체계로 실험적으로 재구성된 마우스)에서 평가되거나 "항원 지수" 알고리즘((Jameson & Wolf (1988) Comput.. Appl. Biosci. 4(1):181-6), 또는 PREDITOP 알고리즘(Pellequer & Westhof, (1993) J. Mol. Graph. 11 (3):204-10)을 통합하는 것과 같은 예측 소프트웨어를 사용하여, 또는 Kolaskar & Tongaonkar의 방법을 사용하여(Kolaskar & Tongaonkar (1990) FEBS Lett. 0:276(1 -2): 172-4, 이의 내용들은 본 명세서에 참고로 포함됨) 예측될 수 있다.
본 발명의 특정 실시형태, 특히 체중 감소, 비만, 탄수화물 대사 및 당뇨병과 관련된 실시형태에 따르면, 본 발명의 화합물, 유도체 및 염은 다음 특징 중 하나, 몇 가지 또는 전부를 갖는다:
A. 1 ml 미만, 0.5 ml 미만 또는 0.3 ml 미만의 용량으로 유효 용량이 투여될 수 있도록 하는 pH 4와 pH 5 사이에서 충분한 용해도;
B. 인간 GLP-1 수용체를 과발현하는 중국 햄스터 난소 세포에서 cAMP 신호전달의 활성화;
C.
상기에 나열된 추가 1 내지 6의 기능 중 하나, 여러 개 또는 전부.
약동학, 작용 지속시간 및 용해도
본 발명의 화합물은 피하 투여 후 생체내에서 강력하고 연장된 작용 지속시간을 나타낸다. 이를 달성하기 위해 화합물은 생물학적 표적에서 우수한 활성과 우수한 약동학적 특성을 모두 갖도록 요구된다.
본 발명의 화합물은 치료적으로 유용한 작용 지속시간을 가지며, 이는 수일에 걸쳐 본 명세서에 기재된 실험에서 관찰되는 유익한 효과에서 그 자체로 명백해진다. 본 발명의 화합물의 반감기를 돼지 PK 모델에서 평가하였다. 본 발명의 바람직한 화합물은 세마글루티드보다 상당히 더 긴 반감기를 갖는 것으로 밝혀졌다. 긴 생체내 반감기를 나타낼 뿐만 아니라, 본 발명의 화합물은 양호한 저장 안정성을 가지며, 4℃에서 4주 동안 용액에 저장할 때 현저한 분해가 보이지 않는다.
불량한 수용해도는 지질 함유 분자에 대해 알려진 문제이다. 대조적으로, 본 발명의 화합물은 매우 양호한 용해도를 갖는다.
본 발명의 특정 화합물은 His 잔기를 포함한다. 수용성이 불량한 펩티드에 His 잔기(들)를 혼입하면 일반적으로 하전된 His 측쇄 기의 존재로 인해 산성 pH(예: pH 5)에서 향상된 용해도를 갖지만 생리학적 pH(pH 7.4)에서 덜 용해가능한 펩티드를 생성한다. 히스티딘 측쇄 기의 pl은 약 6.0이다. 이러한 특성은 약산성 매질에서 His 함유 펩티드의 제형화를 가능하게 한다. 이러한 제형의 피하 주사 시, 용해도가 떨어져서 시간이 지남에 따라 재가용화되는 펩티드의 피하 침전을 초래한다. His 함유 펩티드의 아연 함유 제형은, pH 7.4에서 - 그러나 pH 5에서는 아님 - 아연 이온이 히스티딘 잔기와 배위하고 용해도를 추가로 감소시켜, 피하 주사 부위에서 침전 증가에 기여할 수 있거나 또는 침전물의 안정성 증가에 기여할 수 있기 때문에 이 효과를 향상시킨다. 그러나, 펩티드의 침전이 피하 투여 후 충분히 빠르지 않은 경우, 펩티드의 혈중 농도 수준에서 여전히 초기 "스파이크" 또는 "버스트"가 있을 수 있다. 이러한 특성은 대상체가 비록 일시적일지라도 구토와 같은 고농도 수준의 펩티드와 관련된 부작용을 경험할 가능성을 증가시키기 때문에 바람직하지 않다. 본 발명의 다중-His 함유 C-말단 서열을 갖지 않는 펩티드와 대조적으로, 본 화합물은 피하 투여 후 혈장 농도 수준에서 초기 "스파이크" 또는 "버스트"를 나타내지 않거나 임의의 이러한 "버스트"가 상당히 감소된다. 이는 화합물의 높은 순환 수준과 관련된 가능한 부작용의 가능성 및/또는 심각도를 감소시킨다.
병태
본 발명은 또한 약제로서 사용하기 위한 본 발명의 화합물, 유도체 또는 염, 또는 본 발명의 화합물, 유도체 또는 염과 함께 약제학적으로 허용가능한 담체 및 선택적으로 추가의 치료제를 포함하는 조성물을 제공한다.
본 발명은 또한 치료적 유효량의 본 발명의 화합물, 유도체 또는 염의 투여, 또는 화합물, 유도체 또는 염과 함께 약제학적으로 허용가능한 담체 및 선택적으로 추가의 치료제를 포함하는 조성물의 투여를 포함하는, 대상체에서 질환 또는 장애 또는 다른 원치 않는 생리학적 상태를 치료 또는 예방하는 방법을 제공한다.
바람직하게는, 화합물, 유도체, 염 또는 조성물은 피하로 투여된다.
특정 실시형태에 따르면, 질환 또는 장애 또는 다른 원치 않는 생리학적 상태는 당뇨병 또는 비만, 및 특히 당뇨병(예를 들어, 제II형 당뇨병)이다.
특정 실시형태에 따르면, 질환 또는 장애 또는 다른 원치 않는 생리학적 상태는 과체중인 생리학적 상태일 수 있다.
화합물이 투여되는 대상체는 과체중, 예를 들어 비만일 수 있다. 대안적으로 또는 추가적으로, 대상체는 예를 들어 인슐린 저항성 또는 포도당 불내성, 또는 둘 모두를 갖는 당뇨병일 수 있다. 대상체는 진성 당뇨병을 가질 수 있으며, 예를 들어, 대상체는 제II형 당뇨병을 가질 수 있다. 대상체는 과체중, 예를 들어 비만일 수 있고, 진성 당뇨병, 예를 들어 제II형 당뇨병을 갖는다.
추가적으로 또는 대안적으로, 대상체는 비만 또는 과체중이 위험 인자인 장애를 가질 수 있거나 가질 위험이 있을 수 있다. 이러한 장애는 심장 질환, 심혈관 질환, 예를 들어 고혈압, 죽상동맥경화증, 울혈성 심부전, 및 이상지질혈증; 뇌졸중; 담낭 질환; 골관절염; 수면 무호흡증; 생식 장애, 예를 들어 다낭성 난소 증후군; 암, 예를 들어 유방암, 전립선암, 결장암, 자궁내막암, 신장암, 및 식도암; 정맥류; 흑색가시세포증; 습진; 운동 불내성; 인슐린 저항성; 고혈압 고콜레스테롤혈증; 담석증; 골관절염; 정형외과적 부상; 인슐린 저항성, 예를 들어 제2형 당뇨병 및 증후군 X; 및 혈전색전증을 포함하지만 이에 제한되지 않는다(문헌[Kopelman, Nature 404:635-43, 2000; Rissanen et al., British Med. J. 301, 835, 1990] 참조).
비만과 관련된 다른 장애로는 우울증, 불안, 공황 발작, 편두통, PMS, 만성 통증 상태, 섬유근육통, 불면증, 충동성, 강박 장애 및 근간대 경련을 포함한다. 특정 신경학적 장애 및 특정 신경학적 퇴행도 비만과 관련이 있다.
또한, 비만은 전신 마취의 합병증 발병률 증가에 대한 인식된 위험 인자이다(예를 들어, 문헌[Kopelman, Nature 404:635-43, 2000] 참조). 일반적으로 비만은 수명을 단축시키고 상기에 나열된 것과 같은 동반 질환의 심각한 위험을 수반한다.
비만과 관련된 다른 질환 또는 장애는 선천적 결손증, 신경관 결손증의 발병률 증가와 관련된 산모의 비만, 수근관 증후군(CTS); 만성 정맥 부전(CVI); 주간 졸음; 심부 정맥 혈전증(DVT); 말기 신장 질환(ESRD); 통풍; 열 장애; 손상된 면역 반응; 호흡 기능 장애; 불임; 간 질환; 요통; 산과 및 부인과 합병증; 췌장염; 뿐만 아니라 복강내 헤르니아; 흑색가시세포증; 내분비 이상; 만성 저산소증 및 고칼슘혈증; 피부과 효과; 코끼리발; 위식도 역류; 발뒤꿈치바닥통증; 하지 부종; 브래지어 끈 통증, 피부 손상, 자궁 경부 통증, 만성 악취 및 유방 아래 피부 주름의 감염 등과 같은 상당한 문제를 일으키는 유방 비대증; 큰 전방 복벽 종괴, 예를 들어 빈번한 지방층염을 동반한 복부 지방층염, 보행 방해, 빈번한 감염, 악취, 의복 장애, 요통 유발; 근골격계 질환; 가뇌종양(또는 양성 두개내 고혈압) 및 활주 열공 헤르니아이다.
일부 실시형태에서, 질환 또는 장애는 비-알코올성 지방간 질환일 수 있다.
특정 실시형태에 따르면, 질환 또는 장애 또는 다른 원치 않는 생리학적 상태는 비만 또는 과체중이지 않은 것에도 불구하고 원치 않는 체중의 것일 수 있다. 대상체는 정상 체중일 수 있다(이는 이전에 과체중 또는 비만이었고 건강하지 않은 체중으로 돌아가는 것을 방지하고자 하는 대상체를 포함하지만 이에 제한되지 않음). 대상체는 체중 감량을 원하는 대상체, 예를 들어 외모의 변화를 원하는 여성 및/또는 남성 대상체일 수 있다. 대상체가 정상 체중인 일부 경우에, 본 발명의 양태는 치료적 치료보다는 미용적 치료에 관한 것일 수 있다.
본 발명은 또한 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 조성물을 투여하는 단계를 포함하는, 대상체에서 식욕 감소, 대상체에서 음식 섭취량 감소, 대상체에서 칼로리 섭취 감소, 대상체에서 인슐린 방출 개선, 대상체에서 탄수화물 대사 개선 및/또는 대상체에서 탄수화물 내성 개선 방법을 제공한다. 이러한 방법은 인슐린 무감각 또는 당뇨병 전단계와 같은 당뇨병 전 상태를 가진 대상체를 치료하는 것과 관련될 수 있다.
본 발명은 또한 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 조성물을 투여하는 단계를 포함하는 대상체에서 지질 프로파일을 개선하는 방법을 제공한다. 본 발명은 또한 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 조성물을 투여하는 단계를 포함하는, 영양소 이용가능성을 감소시킴으로써 경감될 수 있는 병태 또는 장애를 경감시키는 방법을 제공한다.
본 발명의 화합물, 유도체, 염 또는 조성물은 체중 조절 및 치료, 예를 들어 비만의 감소 또는 예방, 특히 다음 중 임의의 하나 이상을 위해 사용될 수 있다: 체중 증가의 예방 및 감소; 체중 감소 유도 및 촉진; 및 체질량 지수로 측정한 비만 감소. 본 발명의 화합물, 유도체, 염 또는 조성물은 원하는 체중, 원하는 체질량 지수, 원하는 외모 및 양호한 건강 중 임의의 하나 이상을 유지하는데 사용될 수 있다.
본 발명은 또한 상대적으로 높은 영양소 이용가능성에 의해 야기되거나, 복잡하게 되거나, 악화되는 병태 또는 장애를 치료, 예방, 개선 또는 경감시키는데 사용될 수 있다. 용어 "칼로리(또는 영양소) 이용가능성을 감소시킴으로써 경감될 수 있는 병태 또는 장애"는 본 명세서에서 상대적으로 높은 영양소 이용가용성에 의해 야기되거나, 복잡하게 되거나, 악화되거나, 또는 영양소 이용가능성을 감소시킴으로써 예를 들어 음식 섭취량을 줄임으로써 경감될 수 있는 대상체의 임의의 병태 또는 장애를 나타내기 위해 사용된다. 인슐린 저항성, 포도당 불내성 또는 임의의 형태의 진성 당뇨병, 예를 들어 1형, 2형 또는 임신성 당뇨병을 앓는 대상체는 또한 본 발명에 따른 방법으로부터 이익을 얻을 수 있다.
증가된 칼로리 섭취와 관련된 병태 또는 장애에는 인슐린 저항성, 포도당 불내성, 비만, 2형 당뇨병을 포함한 당뇨병, 섭식 장애, 인슐린 저항성 증후군 및 알츠하이머병이 포함되나 이에 제한되지 않는다.
J. Cereb. Blood Flow Metab. 2011 Apr 13 (Teramoto S et al.)은 심근 경색 후 심장 보호를 부여하기 위해 GLP-1 및 엑센딘-4 모두의 사용에 대해 논의하고 엑센딘-4가 대뇌 허혈-재관류 손상에 대한 신경 보호를 제공하는 데 사용될 수 있음을 입증한다. 이 연구는 60분 국소 뇌 허혈 후 엑센딘-4의 경정맥 주사를 받은 마우스가 경색 부피를 상당히 감소시키고 기능적 결핍을 개선했을 뿐만 아니라 재관류 후 산화 스트레스, 염증 반응 및 세포 사멸을 억제한 것으로 나타났다. 이 연구는 엑센딘-4의 보호 효과가 증가된 세포내 cAMP 수준을 통해 매개된다는 증거를 제공했으며, 엑센딘-4가 급성 허혈성 뇌졸중의 치료에 잠재적으로 유용함을 시사했다.
따라서, 본 발명은 또한 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 조성물을 투여하는 단계를 포함하는, 대상체에서 세포 보호 제공, 예를 들어 심장 보호 제공, 신경보호 제공 및/또는 신경퇴행의 치료 또는 예방 방법을 제공한다.
특정 실시형태에서, 본 발명의 화합물, 유도체, 염 또는 조성물을 사용하여 치료 또는 예방할 수 있는 질환 또는 장애 또는 기타 원치 않는 생리학적 상태는 신경퇴행이다. 이러한 신경퇴행은 바람직하게는 CNS에서 신경 세포의 세포자멸, 괴사 또는 기능 상실에 의해 야기될 수 있다.
치료 또는 예방되는 신경퇴행은 뇌 손상(예를 들어 뇌졸중, 뇌종양, 감염, 중독, 저산소증, 허혈, 뇌병증 또는 약물 남용과 같은 신체적 외상 또는 비외상적 손상 이후의 것) 이후의 것일 수 있습니다. 대안적으로 또는 추가적으로, 신경퇴행은 알츠하이머병, 파킨슨병, 게릭병(근위축성 측색 경화증), 헌팅턴병, 다발성 경화증, 기타 탈수초 관련 장애, 노인성 치매, 피질하 치매, 동맥경화성 치매, AIDS 관련 치매, 기타 치매, 뇌혈관염, 간질, 뚜렛 증후군, 길랭 바레 증후군, 윌슨병, 피크병, 신경염증성 장애, 뇌염, 뇌척수염, 수막염, 기타 중추신경계 감염, 프리온 질환, 소뇌 운동실조, 소뇌 변성, 척수소뇌 변성 증후군, 프리드리히 운동실조, 모세혈관 확장성 운동실조(ataxia teangiectasia), 척수 근위축증, 진행성 핵상 마비, 근육긴장이상, 근육 경직, 떨림, 색소성 망막염, 선조체 흑질 변성, 미토콘드리아 뇌근병증, 신경원세로이드 리포푸신증과 같은 신경퇴행을 갖는(또는 소인이 있는 것으로 진단된) 대상체에서 예방 또는 치료될 수 있다. 바람직하게는, 신경퇴행성 질환은 알츠하이머병, 파킨슨병, 게릭병(근위축성 측색 경화증) 및 헌팅턴병으로 이루어진 군으로부터 선택된다. 그러한 상황에서, 치료는 신경보호적으로 간주될 것이다. 특정 바람직한 실시형태에 따르면, 치료는 뇌 허혈 후 신경보호적이거나 신경퇴행성 질환을 앓거나 신경퇴행성 질환에 대한 소인을 갖는 것으로 진단된 대상체에서 신경보호적이다.
다른 실시형태에 따르면, 질환 또는 장애 또는 다른 원치 않는 생리학적 상태는 심장 변성(특히 심근 세포의 세포자멸, 괴사 또는 기능 상실)이며, 이 경우에 본 발명에 따른 화합물, 유도체, 염 또는 조성물은 심장 보호를 제공한다.
특정 바람직한 실시형태에 따르면, 치료는 심근 경색 후 심근 기능의 보호이다.
본 발명은 또한 비만 또는 당뇨병의 치료에 사용하기 위한 본 발명의 화합물, 유도체, 염 또는 조성물을 제공한다.
본 발명은 또한 대상체의 에너지 소비를 증가, 대상체에서 인슐린 방출을 개선, 대상체에서 탄수화물 내성을 개선하고/하거나 대상체에서 탄수화물 대사를 개선하는데 사용하기 위한 본 발명의 화합물, 유도체, 염 또는 조성물을 제공한다. 이러한 용도는 인슐린 무감각 또는 당뇨병 전단계와 같은 당뇨병 전 상태를 가진 대상체를 치료하는 것과 관련될 수 있다.
본 발명은 또한 대상체에서 식욕을 감소시키는 데 사용하기 위한, 대상체에서 음식 섭취량을 감소시키는 데 사용하기 위한, 대상체에서 칼로리 섭취를 감소시키는 데 사용하기 위한, 대상체에서 인슐린 방출을 개선하는 데 사용하기 위한 및/또는 대상체에서 탄수화물 내성을 개선하는 데 사용하기 위한, 본 발명의 화합물, 유도체, 염 또는 조성물을 제공한다. 이러한 용도는 인슐린 무감각 또는 당뇨병 전단계와 같은 당뇨병 전 상태를 가진 대상체를 치료하는 것과 관련될 수 있다.
본 발명은 또한 (예를 들어, 신경퇴행을 치료 또는 예방하고/하거나 신경보호를 제공하고/하거나 심장 보호를 제공하는 데 있어서) 세포보호제로서 사용하기 위한 본 발명의 화합물, 유도체, 염 또는 조성물을 제공한다. 예를 들어, 화합물, 유도체, 염 또는 조성물은 심근 경색 후 대상체에서 심근 보호에 사용하기 위한 것, 또는 뇌 허혈 또는 뇌졸중 후 대상체에서 신경보호에 사용하기 위한 것, 또는 만성 신경퇴행성 질환을 앓는 대상체에서 신경보호에 사용하기 위한 것일 수 있다. 화합물, 유도체, 염 또는 조성물의 신경보호 또는 심장보호 용도의 다양한 특징은 본 발명의 방법과 관련하여 상기에 약술된 바와 같을 수 있다.
신경보호의 경우, 대상체는 이전에 뇌 손상, 뇌졸중 또는 뇌 허혈을 유발하는 다른 사건을 경험했을 수 있다. 대안적으로, 대상체는 만성 신경퇴행성 질환을 발병할 소인을 갖거나 이로 진단받았을 수 있다. 심장 보호의 경우 대상체는 이전에 심근 경색 및 협심증과 같은 심근 허혈을 유발하는 사건을 경험했을 수 있다.
일부 실시형태에 따르면, 본 발명의 화합물, 유도체, 염 또는 조성물은 대상체가 의심되는 심근 경색을 경험한 후 가능한 한 빨리 투여될 수 있다. 특정 실시형태에 따르면, 본 발명의 화합물, 유도체, 염 또는 조성물은 대상체가 의심되는 뇌졸중을 경험한 후 가능한 빨리 투여될 수 있다.
본 발명은 또한 본 발명의 다른 양태와 관련하여 상기 기재된 바와 같을 수 있는 대상체의 비만 또는 당뇨병 치료를 위한 약제의 제조를 위한 본 발명의 화합물, 유도체, 염 또는 조성물의 용도를 제공한다.
본 발명은 또한 대상체에서 인슐린 방출을 개선하기 위한, 대상체에서 탄수화물 내성을 개선하기 위한 및/또는 대상체에서 탄수화물 대사를 개선하기 위한 약제의 제조를 위한 본 발명의 화합물, 유도체 또는 염의 용도를 제공한다. 이러한 용도는 인슐린 무감각 또는 당뇨병 전단계와 같은 당뇨병 전 상태를 가진 대상체를 치료하는 것과 관련될 수 있다.
본 발명은 또한 대상체에서 식욕을 감소시키기 위한, 대상체에서 음식 섭취량을 감소시키기 위한, 대상체에서 칼로리 섭취를 감소시키기 위한, 대상체에서 인슐린 방출을 개선하기 위한, 및/또는 대상체에서 탄수화물 내성을 개선하는 데 사용하기 위한 약제의 제조를 위한 본 발명의 화합물, 유도체 또는 염의 용도를 제공한다.
본 발명은 또한 본 발명의 다른 양태와 관련하여 상기 기재된 바와 같을 수 있는 대상체의 세포보호(예를 들어, 신경퇴행의 예방 또는 치료, 신경보호 제공 및/또는 심장 보호 제공)를 제공하기 위한 약제의 제조를 위한 본 발명의 화합물, 유도체 또는 염의 용도를 제공한다.
특정 실시형태에 따르면, 본 발명의 화합물, 유도체, 염 또는 조성물은 비경구 투여된다. 다른 실시형태에 따르면, 본 발명의 화합물, 유도체, 염 또는 조성물은 피하, 정맥내, 근육내, 비강내, 경피 또는 설하로 투여된다. 다른 실시형태에 따르면, 본 발명의 화합물, 유도체, 염 또는 조성물은 경구 투여된다. 바람직한 일 실시형태에서, 본 발명의 화합물, 유도체, 염 또는 조성물은 피하로 투여된다.
본 발명의 화합물, 유도체, 염 또는 조성물은 바람직하게는 인간 대상체의 치료에 사용된다. 그러나, 본 발명의 화합물, 유도체, 염 또는 조성물은 전형적으로 인간 대상체를 치료하는데 사용될 것이지만, 그들은 또한 다른 척추동물, 예를 들어 다른 영장류; 농장 동물 예를 들어 돼지, 소 및 가금류; 스포츠 동물 예를 들어 말; 또는 반려 동물 예를 들어 개와 고양이에서 유사하거나 동일한 병태를 치료하는데 사용될 수 있다.
조성물
식 (I)의 화합물, 또는 이의 유도체 및/또는 염은 약제학적 제형 또는 조성물에 존재하는 것이 바람직하다. 따라서, 본 발명은 본 발명의 화합물, 유도체 또는 염을 약제학적으로 허용가능한 부형제 및 선택적으로 다른 치료 성분과 함께 포함하는 조성물을 제공한다. 화합물, 유도체 또는 염을 포함하는 조성물은 약제학적 용도에 적합하다. 특정 바람직한 실시형태에 따르면, 조성물은 인간에게 피하 투여를 위해 주사기 또는 다른 투여 장치에 존재한다. 특정 바람직한 실시형태에 따르면, 조성물은 pH가 5 미만이다. 본 발명의 조성물은 하기 기재된 바와 같은 약제학적 제형의 형태를 취할 수 있다.
본 발명에 따른 약제학적 제형은 경구, 비경구(피하, 진피내, 근육내, 정맥내, 및 관절내 포함), 흡입(다양한 유형의 정량 가압 에어로졸, 네뷸라이저 또는 취입기에 의해 생성될 수 있는 미립자 분진 또는 미스트 포함), 직장 및 국소(진피, 경피, 경점막, 볼, 설하, 및 안구내 포함) 투여에 적합한 것들을 포함하지만, 가장 적합한 경로는 예를 들어, 수용체의 병태 및 장애에 의존할 수 있다.
제형은 단위 투여 형태로 편리하게 제공될 수 있고, 조제약 분야에서 잘 알려진 방법에 의해 제조될 수 있다. 모든 방법은 활성 성분을 하나 이상의 부속 성분을 구성하는 담체와 회합시키는 단계를 포함한다. 일반적으로 제형은 활성 성분을 액체 담체 또는 미분된 고체 담체 또는 둘 모두와 균일하고 밀접하게 회합시킨 다음, 필요한 경우, 생성물을 원하는 제형으로 형상화함으로써 제조된다.
경구 투여에 적합한 본 발명의 제형은 미리 결정된 양의 활성 성분을 각각 함유하는 캡슐, 카세(cachet), 또는 정제와 같은 별개의 단위로서; 분말 또는 과립으로서; 수성 액체 또는 비수성 액체 중의 용액 또는 현탁액으로서; 또는 수중유 액체 에멀젼 또는 유중수 액체 에멀젼으로서 제공될 수 있다. 활성 성분은 또한 볼러스, 연약 또는 페이스트로서 제공될 수 있다. 다양한 약제학적으로 허용가능한 담체 및 이들의 제형은 표준 제형 조약, 예를 들어, 문헌[Remington's Pharmaceutical Sciences by E. W. Martin]에 기재되어 있다. 또한, 문헌[Wang, Y. J. and Hanson, M. A., Journal of Parenteral Science and Technology, Technical Report No. 10, Supp. 42:2S, 1988]에 기재되어 있다.
정제는 선택적으로 하나 이상의 부속 성분과 함께 압축 또는 성형에 의해 제조될 수 있다. 압축 정제는 결합제, 윤활제, 불활성 희석제, 윤활제, 표면 활성 또는 분산제와 선택적으로 혼합된, 분말 또는 과립과 같은 자유-유동 형태의 활성 성분을 적합한 기계에서 압축함으로써 제조될 수 있다. 성형된 정제는 불활성 액체 희석제로 습윤화된 분말 화합물의 혼합물을 적합한 기계에서 성형함으로써 제조될 수 있다. 정제는 선택적으로 코팅되거나 눈금새겨질 수 있고, 그 안에 활성 성분의 느린 또는 조절된 방출을 제공하도록 제형화될 수 있다. 본 발명의 화합물은 예를 들어 즉시 방출 또는 연장 방출에 적합한 형태로 투여될 수 있다. 즉시 방출 또는 연장 방출은 본 발명의 화합물을 포함하는 적합한 약제학적 조성물의 사용에 의해, 또는 특히 연장 방출의 경우, 피하 이식물 또는 삼투 펌프와 같은 장치의 사용에 의해 달성될 수 있다. 본 발명의 화합물은 또한 리포좀으로 투여될 수 있다.
바람직하게는, 본 발명에 따른 조성물은 예를 들어 주사에 의한 피하 투여에 적합하다. 특정 실시형태에 따르면, 조성물은 금속 이온, 예를 들어 구리, 철, 알루미늄, 아연, 니켈 또는 코발트 이온을 함유할 수 있다. 이러한 이온의 존재는 용해도를 제한할 수 있으므로 피하 투여 부위에서 순환계로의 흡수를 지연시킬 수 있다.
경구 투여를 위한 예시적인 조성물은 예를 들어 벌크를 부여하기 위한 미세결정질 셀룰로오스, 현탁제로서의 알긴산 또는 알긴산나트륨, 점도 증진제로서의 메틸셀룰로오스, 및 감미제 또는 향미제, 예컨대 당업계에 공지된 것들을 함유할 수 있는 현탁액; 및 예를 들어, 미세결정성 셀룰로오스, 인산제이칼슘, 전분, 스테아르산마그네슘, 및/또는 락토스 및/또는 다른 부형제, 결합제, 증량제, 붕해제, 희석제 및 윤활제 예컨대 당해 분야에서 알려진 것들을 포함할 수 있는 즉시 방출 정제를 포함한다. 그러한 조성물은 또한 투과 증진제를 포함할 수 있다. 본 발명의 화합물은 또한 설하 및/또는 협측 투여에 의해 구강을 통해 또한 전달될 수 있다. 성형 정제, 압축 정제 또는 동결-건조 정제는 사용될 수 있는 예시적인 형태이다. 예시적인 조성물은 본 화합물(들)을 속용성 희석제 예컨대 만니톨, 락토스, 수크로스 및/또는 사이클로덱스트린으로 제형화하는 것을 포함한다. 또한 이러한 제형에는 고분자량 부형제 예컨대 셀룰로오스 (아비셀) 또는 폴리에틸렌 글리콜 (PEG)이 포함될 수 있다. 이러한 제형은 또한 점막 부착을 돕기 위한 부형제 예컨대 하이드록시프로필 셀룰로오스 (HPC), 하이드록시프로필 메틸 셀룰로오스 (HPMC), 나트륨 카르복시 메틸 셀룰로오스 (SCMC), 말레산 무수물 공중합체 (예를 들어 Gantrez), 및 방출을 조절하기 위한 제제 예컨대 폴리아크릴산 공중합체 (예를 들어 Carbopol 934)를 포함할 수 있다. 윤활제, 활택제, 풍미제, 착색제 및 안정화제가 또한 제조 및 사용의 용이성을 위해 첨가될 수 있다.
비경구 투여용 제형은 항산화제, 완충제, 정균제 및 제형이 의도된 수용체의 혈액과 등장성이 되게 하는 용질을 함유할 수 있는 수성 및 비수성 멸균 주사 용액; 및 현탁화제 및 증점제를 포함할 수 있는 수성 및 비-수성 멸균 현탁액을 포함한다. 제형은 단위-용량 또는 다중-용량 용기, 예를 들어 밀봉된 앰풀 및 바이알로 제공될 수 있고, 사용 직전에 멸균 액체 담체, 예를 들면 염수 또는 주사용수의 첨가만을 필요로 하는 냉동건조된 (동결건조된) 상태로 보관될 수 있다. 즉석 주사액 및 현탁액은 이전에 기재된 종류의 멸균 분말, 과립 및 정제로부터 제조될 수 있다. 비경구 투여를 위한 예시적인 조성물은 예를 들어, 적합한 무독성의 비경구적으로 허용 가능한 희석제 또는 용매, 예컨대, 만니톨, 1,3-부탄다이올, 물, 링거액, 등장성 염화나트륨 용액, 또는 합성 모노글리세리드 또는 디글리세리드를 비롯한 다른 적합한 분산제 또는 습윤제 및 현탁화제 및 올레산을 비롯한 지방산 또는 Cremaphor를 함유할 수 있는 주사 용액 또는 현탁액을 포함한다. 수성 담체는 예를 들어 pH 약 3.0 내지 약 8.0, 바람직하게는 pH 약 3.5 내지 약 7.4, 예를 들어 3.5 내지 6.0, 예를 들어 3.5 내지 약 5.0의 등장 완충 용액일 수 있다. 유용한 완충제에는 시트르산나트륨-시트르산 및 인산나트륨-인산, 및 아세트산나트륨/아세트산 완충제가 포함된다. 조성물은 바람직하게는 펩티드 화합물에 유해한 것으로 알려진 임의의 화합물을 포함하지 않는다.
포함될 수 있는 부형제는 예를 들어 인간 혈청 알부민 또는 혈장 제제와 같은 다른 단백질이다. 원하는 경우, 약제학적 조성물은 또한 습윤제 또는 유화제, 방부제 및 pH 완충제 등과 같은 비독성 보조 물질, 예를 들어 아세트산나트륨 또는 소르비탄 모노라우레이트를 소량 함유할 수 있다.
비강 에어로졸 또는 흡입 투여를 위한 예시적인 조성물은 예를 들어, 벤질 알코올 또는 다른 적합한 방부제, 생체이용률을 증강시키기 위해 흡수 촉진제 및/또는 다른 가용화제 또는 분산제, 예컨대 당업계에 알려진 것들을 함유할 수 있는 식염수 중 용액을 포함한다. 편리하게는 비강 에어로졸 또는 흡입 투여를 위한 조성물에서, 본 발명의 화합물은 적합한 추진제, 예를 들어 다이클로로다이플루오로-메탄, 트라이클로로플루오로메탄, 다이클로로테트라플루오로에탄, 이산화탄소 또는 다른 적합한 가스를 사용하여, 가압 팩 또는 네뷸라이저로부터 에어로졸 분무 제시의 형태로 전달된다. 가압 에어로졸의 경우, 투여량 단위는 계량된 양을 전달하기 위해 밸브를 제공함으로써 결정될 수 있다. 예를 들어 흡입기 또는 취입기에 사용하기 위한 젤라틴의 캡슐 및 카트리지는 화합물과 적합한 분말 베이스, 예를 들어 락토스 또는 전분의 분말 혼합물을 함유하도록 제형화될 수 있다. 하나의 특정 비제한적인 예에서, 본 발명의 화합물은 액추에이터로도 알려진 에어로졸 어댑터를 통해 계량 용량 밸브로부터 에어로졸로서 투여된다. 선택적으로, 안정제가 또한 포함되고/되거나 깊은 폐 전달을 위한 다공성 입자가 포함된다(예를 들어, 미국 특허 제6,447,743호 참조).
직장 투여를 위한 제형은 코코아 버터, 합성 글리세라이드 에스테르 또는 폴리에틸렌 글리콜과 같은 통상의 담체와 함께 보유 관장 또는 좌제로 제시될 수 있다. 이러한 담체는 전형적으로, 통상적인 상온에서 고체이지만, 직장강(rectal cavity) 내에서 액화 및/또는 용해되어 약물을 방출시킨다.
입안, 예를 들어 협측으로 또는 설하로 국소 투여를 위한 제형은, 풍미 기재 예컨대 수크로스 및 아카시아 또는 트라가칸트에 활성 성분을 포함하는 로젠지, 및 기재 예컨대 젤라틴 및 글리세린 또는 수크로스 및 아카시아에 활성 성분을 포함하는 사탕형 환제를 포함한다. 국소 투여에 예시적인 조성물은 국소 담체, 예컨대, Plastibase(폴리에틸렌으로 겔화된 미네랄 오일)를 포함한다.
바람직한 단위 투약 제형은 활성 성분의 상기 언급된 바와 같은 유효 용량 또는 그의 적절한 분획을 함유하는 것이다.
특히 상기 언급된 성분 이외에, 본 발명의 제형은 해당 제형의 유형에 관하여 당해 분야에 통상적인 다른 제제를 포함할 수 있으며, 예를 들어 경구 투여에 적합한 제형이 향미제를 포함할 수 있다는 것을 이해하여야 한다.
본 발명의 화합물, 유도체 및 염은 또한 지속 방출 시스템으로서 적합하게 투여될 수 있다. 본 발명의 지속 방출 시스템의 적합한 예에는 적합한 고분자 재료, 예를 들어, 형상화된 물품, 예를 들어 필름, 또는 마이크로캡슐의 형태의 반투과성 고분자 매트릭스; 예를 들어 허용가능한 오일 중의 에멀젼으로서 적합한 소수성 재료; 또는 이온 교환 수지; 및 본 발명의 화합물의 난용성 유도체, 예를 들어, 난용성 염이 포함된다. 지속 방출 시스템은 경구; 직장; 비경구; 수조내(intracisternally); 질내; 복강내; 국소적으로, 예를 들어, 분말, 연고, 겔, 점적제 또는 경피 패치로서, 협측으로; 또는 경구 또는 비강 분무제로서 투여될 수 있다.
투여용 제제는 본 발명의 화합물, 유도체 및 염의 제어 방출을 제공하도록 적합하게 제형화될 수 있다. 예를 들어, 약제학적 조성물은 생분해성 중합체, 다당류 젤리화 및/또는 생체접착성 중합체, 양친매성 중합체, 본 발명의 화합물 입자의 계면 특성을 개질할 수 있는 제제 중 하나 이상을 포함하는 입자 형태일 수 있다. 이들 조성물은 활성 물질의 제어 방출을 가능하게 하는 특정 생체적합성 특징을 나타낸다(미국 특허 제5,700,486호를 참조, 이의 내용은 참조로 포함됨).
제어 방출 조성물의 사용은 비만 및/또는 당뇨병의 치료와 같은 적응증에 바람직하며, 주사 사이의 시간을 최대화하는 것이 바람직하다. 그러나 가능한 한 짧은 시간 내에 활성제의 치료적 혈장 농도를 달성하는 것이 바람직한 신경보호 또는 심장 보호(예를 들어, 의심되는 심근 경색 또는 뇌졸중 후)를 제공하는 것과 같은 적응증의 경우, 즉시 방출 제형이 바람직할 것이다. 그러한 경우에, 활성제의 즉시 방출 제형의 용량 투여(즉, 의심되는 심근 경색 또는 뇌졸중 후 가능한 한 빨리) 및 활성제의 제어 방출 제형의 용량의 후속 투여를 포함하는 투여 요법이 바람직할 수 있다.
본 발명의 화합물, 유도체 또는 염은 펌프를 통해(문헌[Langer, supra, Sefton, CRC Crit. Ref. Biomed. Eng. 14:201, 1987; Buchwald et al., Surgery 88:507, 1980]; 문헌[Saudek et a/., N. Engl. J. Med. 321 :574, 1989] 참조) 또는 예를 들어 미니 펌프를 사용하는 연속 피하 주입에 의해 전달될 수 있다. 정맥 백 용액이 또한 사용될 수 있다. 적절한 용량을 선택하는 데 핵심 인자는, 시술자에 의해 적절한 것으로 여겨지는 바와 같이, 총 체중 감소 또는 제지방에 대한 지방 비율, 또는 비만의 조절 또는 예방 또는 비만 관련 병태의 예방을 측정하기 위한 기타 기준에 의해 측정된 바와 같이 얻어진 결과이다. 다른 제어 방출 시스템은 Langer (Science 249:1527-1533, 1990)에 의한 리뷰 논문에서 논의되며, 이는 본 명세서에 참조로 포함된다. 본 발명의 다른 양태에서, 본 발명의 화합물은, 예를 들어 미국 특허 제6,436,091호; 미국 특허 제5,939,380호; 미국 특허 제5,993,414호에 기재된, 이식된 펌프를 통해 전달되며, 상기 문헌의 내용은 본 명세서에 참조로 포함된다.
이식형 약물 주입 장치는 환자에게 약물 또는 기타 치료제를 일정하게 장기간 투약하거나 주입하는 데 사용된다. 본질적으로 그러한 장치는 능동 또는 수동으로 분류될 수 있다. 본 발명의 화합물, 유도체 또는 염은 데포 제제로 제형화될 수 있다. 이러한 장기 작용성 데포 제형은 예를 들어 피하 또는 근육내 이식에 의해; 또는 근육 주사에 의해 투여될 수 있다. 따라서, 예를 들어, 활성 성분은 적합한 중합체 또는 소수성 물질, 예를 들어 허용가능한 오일 또는 이온 교환 수지 중의 에멀젼으로; 또는 난용성 유도체로서, 예를 들어 난용성 염으로서 제형화될 수 있다.
본 발명의 활성제의 치료적 유효량은 단일 펄스 용량, 볼루스 용량 또는 시간 경과에 따른 펄스 용량으로서 투여될 수 있다. 따라서, 펄스 용량에서, 활성제의 볼루스 투여가 제공되고, 대상체에게 활성제가 투여되지 않는 기간이 뒤따르고, 이어서 두 번째 볼루스 투여가 제공된다. 특정 비제한적인 예에서, 펄스 용량은 하루 동안, 일주일 동안 또는 한 달 동안 투여된다.
병용 치료
특정 실시형태에서, 치료적 유효량의 본 발명의 화합물, 유도체, 염 또는 조성물은 치료적 유효량의 추가 제제 또는 제제들과 투여된다. 화합물, 유도체 또는 염은 예를 들어 하나 이상의 추가 치료제(들)와 동시에 투여될 수 있거나, 순차적으로 또는 개별적으로 투여될 수 있다. 따라서, 본 발명은 약제로서 사용하기 위한 본 발명의 화합물, 유도체 또는 염을 제공하며, 여기서 화합물, 유도체 또는 염은 치료적 유효량의 추가 치료제 또는 제제들과 함께 사용하기 위한 것이다(예를 들어, 동시, 순차적 또는 별도 투여를 위해). 특정 실시형태에서, 본 발명의 활성제는 단일 용량으로서 추가의 치료제 또는 제제와 함께 제형화되고 투여된다.
특정 실시형태에서, 추가의 치료제 또는 제제들은 추가적인 항당뇨병제, 식욕 억제제, 음식 섭취 감소제, 혈장 포도당 저하제 또는 혈장 지질 변경제이다. 추가적인 식욕 억제제의 특정 비제한적인 예는 암페프라몬(다이에틸프로피온), 펜터민, 마진돌 및 페닐프로판올아민, 펜플루라민, 덱스펜플루라민, 펜디메트라진, 벤즈페타민, 시부트라민, 리모나반트, 토피라메이트, 플루옥세틴, 부프로피온, 조니사미드, 날트렉손, 오를리스타트 및 세틸리스타트를 포함한다. 추가적인 항당뇨병제의 특정 비제한적인 예는 메트포르민, 펜포르민, 로시글리타존, 피오글리타존, 트로글리타존, 레파글리니드, 나테글리니드, 톨부타미드, 아세토헥사미드, 톨라자미드, 클로르프로파미드, 글리피지드, 글리부리드, 글리메피리드, 글리클라지드, 섬유아세포 성장 인자 21, 미글리톨, 아카르보스, 엑세나티드, 프람린티드, 빌다글립틴 및 시타글립틴을 포함한다.
대안적인 실시형태에서, 추가의 치료제 또는 제제들은 추가의 심장보호제 또는 신경보호제이다. 추가적인 심장보호제의 특정 비제한적인 예는 아스피린, N-아세틸시스테인, 페네틸아민, 조효소 Q10, 비타민 E, 비타민 C, L-카르니틴, 카르베디올 및 덱스라족산을 포함한다. 신경보호제의 특정 비제한적인 예는 스타틴, 예컨대 심바스타틴, 스테로이드, 예컨대 프로게스테론, 미노사이클린, 레스베라트롤 및 비타민 E를 포함한다. 파킨슨병 치료에 사용되는 제제의 예는 항콜린제, 프라미펙솔, 브로모크립틴, 레보도파, 카르비도파, 라사길린, 아만타딘 및 로피니롤을 포함한다.
투여량
본 발명의 화합물, 유도체, 염 또는 조성물은 효과, 예를 들어 식욕 억제, 음식 섭취량 감소 또는 열량 섭취 감소가 필요할 때마다 투여될 수 있거나, 또는 효과가 필요할 때마다 약간 전에, 예를 들어 효과가 필요하기 전 제한되지는 않지만 약 10분, 약 15분, 약 30분, 약 60분, 약 90분, 또는 약 120분 전에 투여될 수 있다.
본 발명의 활성제의 치료적 유효량은 사용되는 분자, 치료되는 대상, 고통의 중증도 및 유형, 투여 방식 및 경로에 따라 달라질 것이다. 예를 들어, 본 발명의 화합물의 치료적 유효량은 체중 킬로그램(㎏)당 약 0.01 ㎍ 내지 체중 ㎏당 약 1g, 예를 들어 체중 ㎏당 약 0.1 ㎍ 내지 약 20 mg, 예를 들어 체중 ㎏당 약 1 ㎍ 내지 약 5 mg, 또는 체중 ㎏당 약 5 ㎍ 내지 약 1 mg으로 다양할 수 있다.
본 발명의 일 실시형태에서, 본 발명의 화합물, 유도체 또는 염은 체중 ㎏당 0.5 내지 1,333 nmol, 예를 들어 1 내지 1,333 nmol/㎏ 체중, 예를 들어, 2 내지 1,000 nmol/㎏ 체중, 예를 들어, 체중 ㎏당 4 내지 1,333 nmol, 예를 들어, 체중 ㎏당 5 내지 1,000 nmol, 예를 들어, 체중 ㎏당 10 내지 750 nmol, 특히 체중 ㎏당 20 내지 500 nmol, 특히 체중 ㎏당 30 내지 240 nmol로 대상체에게 투여될 수 있다. 바람직한 실시형태에서, 본 발명의 고활성 화합물은 체중 ㎏당 0.2 내지 10 nmol, 예를 들어 0.5 내지 5.0 nmol/㎏ 체중, 예를 들어 1.0 내지 2.0 nmol/㎏ 체중, 예를 들어 1.5 nmol/㎏ 체중으로 대상체에 투여된다. 75 ㎏ 대상체에 대해, 이러한 용량은 37.5 nmol 내지 100 μmol, 예를 들어 75 nmol 내지 100 μmol, 예를 들어 150 nmol 내지 100 μmol, 예를 들어 300 nmol 내지 100 μmol, 예를 들어 375 nmol 내지 75 μmol, 예를 들어 750 nmol 내지 56.25 μmol, 예를 들어 1.5 내지 37.5 μmol, 특히 2.25 내지 18 μmol의 투여량에 상응한다. 본 발명의 고활성 화합물에 대한 바람직한 실시형태에서, 75 ㎏ 대상체에 대해, 이러한 용량은 15 내지 750 nmol, 예를 들어 37.5 내지 375.0 nmol, 예를 들어 75 내지 150 nmol, 예를 들어 112.5 nmol의 투여량에 상응한다. 본 발명은 또한 본 명세서에 언급된 임의의 특정 투여량에 의해 경계지어지는 투여 범위를 고려한다.
정확한 용량은 이용되는 특정 화합물의 효력, 화합물의 전달 경로 및 대상체의 연령, 체중, 성별 및 생리학적 상태에 기초하여 당업자에 의해 용이하게 결정된다.
긴 혈중 반감기를 갖는 화합물의 경우, 상기 논의된 용량은 예를 들어 1개월 당 1회 또는 2회, 또는 1주에 1회, 2회, 3회 또는 4회 주어질 수 있다. 바람직한 화합물의 경우, 용량은 1주일에 1회 이하 빈도로 주어질 수 있다. 대안적으로, 혈중 반감기가 더 짧은 화합물의 경우, 상기에 논의된 용량을 예를 들어 1일 1회, 2회, 3회 또는 4회 또는 1주일에 1회 또는 2회 주어질 수 있다. 일부 실시형태에서, 용량은 2, 3 또는 4일마다 1회 주어질 수 있다. 특정 실시형태에 따르면, 이들은 각각의 식사가 취해지기 직전에 투여될 수 있다.
실시예
본 발명은 하기 비제한적 실시예를 참조하여 설명된다.
재료 및 방법
펩티드 합성
트라이사이클릭 아미드 링커 수지에서 펩티드 합성을 수행하였다. 아미노산을 Fmoc 전략을 사용하여 부착하였다. Xaa1 내지 Xaa42로부터의 분자의 일부에 대해, 각각의 아미노산을 C-말단에서 N-말단으로 순차적으로 첨가하였다. 펩티드 커플링은 HBTU와 같은 시약을 사용하여 매개되었다. 수지로부터의 펩티드 절단은 스캐빈저의 존재 하에 트라이플루오로아세트산을 이용해 달성되었다. 두 번째 단계에서, 라이신 42 잔기는 ε-아미노기의 탈보호 후에 그의 ε-아미노기에서 기능화되었다. 이어서, 라이신 42 잔기 상의 사슬을 동일한 아미노산 부착 화학을 사용하여 순차적으로 구축하였다.
펩티드를 역상 HPLC로 정제하였다. 모든 정제된 펩티드에 대해 품질 관리를 수행하고, 대부분의 경우에 펩티드는 2개의 완충제 시스템에서 HPLC에 의해 90% 초과 순도로 나타났다. MALDI-MS는 예상된 분자 이온을 나타냈다.
실시예 합성
표준 Fmoc 화학을 사용하여 다음과 같이 예시 화합물 193(G Ref 6699)을 제조하였다:
1.
수지 제조: 2Cl-Trt 수지 (0.25 mmol, 1.00 eq)에 DCM (8.0 mL) 중의 FMOC- LYS(DDE)-OH (133.15 mg, 250.00 μmol, 1.00 eq) 및 DIEA (193.85 mg, 1.50 mmol, 261.97 μL, 6.00 eq)를 첨가하였다. 혼합물을 N2로 2시간 동안 20℃에서 진탕시키고, 이어서 MeOH (0.25 mL)를 첨가하고, N2로 추가 30분 동안 진탕시켰다. 수지를 DMF (12.0 mL * 3)로 세정하였다. 이어서, DMF (5.00 mL) 중의 20% 피페리딘을 첨가하고, 혼합물을 N2로 20℃에서 30분 동안 진탕시켰다. 이어서, 혼합물을 여과하여 수지를 얻었다. 수지를 DMF (12.0 mL * 5)로 세정하고, 여과하여 수지를 얻었다.
FMOC-LYS(DDE)-OH는 하기 구조를 갖는다:
유리 산을 수지에 부착되고, 피페리딘 탈보호에 의해 다음 커플링을 위한 유리 아미노 말단기를 생성한다.
2.
커플링: DMF (3.00 mL) 중의 FMOC-LYS(BOC)-OH (351.37 mg, 750.00 μmol, 3.00 eq), DIEA (193.85 mg, 1.50 mmol, 261.97 μL, 6.00 eq) 및 HBTU (270.20 mg, 712.50 μmol, 2.85 eq)를 수지에 첨가하고, N2로 30분 동안 20℃에서 진탕시켰다. 이어서, 수지를 DMF (12.0 mL * 3)로 세정하였다.
3.
탈보호: DMF (5.00 mL) 중의 20% 피페리딘을 수지에 첨가하고, 혼합물을 N2로 20℃에서 30분 동안 진탕시켰다. 수지를 DMF (12.0 mL * 5)로 세정하고, 여과하여 수지를 얻었다.
4.
마지막 아미노산이 추가될 때까지 표 1의 시약을 사용하여 단계 2 내지 단계 3을 반복했다(표 1의 반응 반복 #1은 상기 단계 2 및 단계 3에서 나타낸 바와 같이 처음 추가된 Lys 잔기임).
[표 1]
5.
반복 #38에서 BOC-HIS(TRT)-OH의 커플링 후, 3% H2N-NH2/DMF를 첨가하고 30분 동안 반응시켜 Dde를 제거한 다음 반복하였다. 이어서, 혼합물을 배출하고 DMF (15.0 mL)로 5회 세정하였다. Dde 기를 제거한 후, 화합물은 단계 1에서 라이신의 ε-아미노기에 유리 아미노 말단 기를 갖고 이는 다음 커플링에 사용할 수 있다.
6.
이어서, 마지막 시약이 첨가될 때까지(표에서 반응 반복 #40) 표 2의 시약을 사용하여 단계 2 내지 단계 3의 반응을 수행하였다.
[표 2]
*보호된 글루탐산 시약 39는 TBU로 보호된 C-1 산기를 갖기 때문에, 이는 C-5 산에서 라이신 40의 ε-아미노기와 반응한다. 이는 화합물의 Z 부분에서 글루탐산 잔기 부분을 제공하는 것은 FMOC-GLU-OTBU 시약이다:
7.
펩티드 절단 및 정제:
수지를 MeOH(20.0 mL * 2)로 세정하고 진공 하에 건조시켜 2.0 g의 펩티드 수지를 제공하였다. 이어서 22.0 mL의 절단 완충제(92.5% TFA/2.5% Mpr/2.5% TIS/2.5% H2O)를 측쇄 보호된 펩티드 수지가 들어 있는 플라스크에 20℃에서 첨가하고, 혼합물을 2.5시간 동안 교반하였다. 펩티드를 차가운 tert-부틸 메틸에테르(250 mL)로 침전시키고 원심분리하였다(3000 rpm에서 2분). 펩티드 침전물을 tert-부틸 메틸 에테르로 2회 더 세정하였다(100 mL). 미정제 펩티드를 건조시키고, 동일성을 LCMS에 의해 확인하였다.
잔류물을 prep-HPLC(TFA 조건; 30℃, A: 0.075% TFA/H2O, B: CH3CN)로 정제하여 표제 화합물(202.4 mg, 40.66 μmol, 15.32% 수율, 91.03% 순도, TFA)을 백색 고체로서 수득하고 이의 동일성을 LCMS에 의해 확인하였다.
본 명세서에 기재된 모든 다른 펩티드에 대해 등가의 방법을 사용하였다. 예시된 펩티드의 서열 및 다른 구조적 특징은 도 1 내지 도 1bm에 나타나 있다. 이 도면에서, 위치 42에서의 라이신 잔기는 ε 아미노기 상에서 Y 기로 치환되고, Y는 Z-Xaa43-Xaa44-이고(해당 컬럼 내의 블랭크는 잔기가 부재함을 의미함), Z는 하기 구조를 갖는 기이다:
(여기서, R은 C16-C18 알킬렌 또는 알케닐렌 기이고;
R1은 CO2H임).
R(n, n = 16-18)의 알킬렌 또는 알케닐렌 기의 탄소 원자 수는 도 1 내지 도 1bm의 "n(R = Cn)" 열에 표시되어 있다. 도시된 실시예에서, n은 16 또는 18이다.
도 1 내지 도 1bm의 특정의 예시 화합물은 도면의 다른 곳에 열거된 화합물의 중복 제조이고, 'Note' 제목의 열에 'dupl'과 같이 표시된다.
CHO 세포에서 과발현된 인간 GLP-1 수용체에서 펩티드의 수용체 효능
생물학적 활성은 인간 GLP 수용체를 과발현하는 중국 햄스터 난소(CHO) 세포주에서 cAMP 생성을 자극하는 펩티드의 효능에 의해 평가되었다. 분석 당일에 세포를 무혈청 배지에서 8x10-5 세포/mL의 밀도로 96 웰 반면적 플레이트에 플레이팅했다. 상업용 cAMP 키트(Cisbio)를 사용하여 30분의 펩티드 자극 및 추가 1시간 용해 후 HTRF(균질 시간 분해 형광측정) 기술을 통해 세포의 cAMP를 정량화했다. SpectraMax i3x Multi-Mode Detection Platform 플레이트 판독기에서 플레이트를 판독하고 Graph Pad Prism 7.0(또는 그 이상)으로 농도 반응 곡선을 그렸다. 각 펩티드에 대해 EC50 값을 생성하고 그날에 대조군과 비교했다.
생체내 효력 연구: 수컷 래트에서의 단일 용량 섭식 연구
수컷 래트(Charles River Ltd, Margate, UK)를 동물 실험에 사용하였다. 임의로 먹이를 먹인 래트를 개별적으로 IVC 케이지에 수용했다. 동물을 체중별로 층화하여 처리군으로 무작위화하였다. 모든 펩티드 용액은 투여 직전에 신선하게 제조하였다. 대조군 동물에게는 물 5% v/v 물 및 95% NaCl(0.9% w/v)을 투여한 반면 펩티드(1.5, 2, 3 또는 6 nmol/㎏ 체중)는 주사용수에 재현탁시켰다. 펩티드 및 비히클을 피하 주사에 의해 초기 가벼운 단계(0900 내지 1000)에 투여하고 동물에 공지된 양의 음식을 제공했다. 동물은 연구 기간 동안 음식과 물에 자유롭게 접근하였다. 동물의 체중과 남은 음식은 연구 내내, 일반적으로 투약 후 24, 48, 72 및 96시간, 일부 예에서는 168시간에 칭량되었다. 제시된 결과는 투약 후 4일(96시간) 또는 7일(168시간)에 대한 수치이다.
예시 화합물 1 내지 527에 대한 결과를 도 1 내지 도 1bm에 나타내었다. 래트에게 펩티드의 단일 피하 주사를 투여하였다. 용량은 일반적으로 1.5 내지 6 nmol/㎏ 체중이었다. 도 1 내지 도 1bm의 표에서 'n' 열은 해당 화합물이 테스트된 횟수를 나타낸다. 각 테스트는 일반적으로 5마리의 동물 군에 주어진 화합물을 포함했다. 화합물은 음식 섭취를 억제하는 경향과 체중 변화를 일으키는 능력에 대해 평가되었다. 이들의 행동 합계는 도 1 내지 도 1bm에서 "효능"으로 불리는 단일 값으로서 보고된다. 화합물을 세마글루티드/Ozempic과 비교하였다. "효능"의 경우 점수 8은 화합물이 Ozempic과 동일한 효과를 유발함을 의미한다. 8 초과의 점수는 동일한 용량의 Ozempic 또는 Ozempic과 유사하지만 더 낮은 용량의 시험 화합물로 달성한 것보다 음식 섭취 억제 및 체중 감소 및/또는 체중 증가 감소가 더 크다는 것을 나타낸다. 이러한 높은 활성 수준은 화합물을 세마글루티드/Ozempic보다 낮은 용량으로 투여할 수 있게 한다. 어떤 경우에는 용량이 세마클루티드/Ozempic 수준의 1/6, 1/8, 1/10 또는 심지어 1/12일 수 있다.
반감기 평가에 대한 PK 측정
수컷 큰 백색 돼지는 연구 시작(0시간)에 시험 화합물을 단일 피하 주사로 투여받았다. 168시간 동안 돼지로부터 반복적인 혈액 샘플을 채취하고 혈장을 분리하고 -20 내지 -80℃에서 보관했다. 시험 화합물의 혈장 농도는 질량 스펙트럼 분석을 사용하여 정량화하였다. tmax에서 Cmax의 절반까지 걸리는 시간을 계산하였고 화합물의 반감기(t1/2)를 나타낸다. 전형적으로, 제시된 t1/2는 4마리의 개별 동물의 평균이다.
결과
도 1 내지 도 1bm은 본 발명의 예시 화합물에 대한 아미노산 서열 및 기타 구조적 정보를 제공하는 표이다. 예를 들어, 예시 화합물 번호 1은 다음과 같다[서열 번호 1]:
His
AIB
His
Gly
Thr
Phe
Thr
Ser
Asp
Leu
Ser
Lys
Gln
Leu
Glu
Glu
Glu
Ala
Val
Arg
Leu
Phe
Ile
Glu
Trp
Leu
Lys
Asn
Gly
Gly
Pro
Ser
Ser
Gly
Ala
Pro
Pro
Pro
Lys
그리고 위치 42에서의 Lys 잔기는 ε-아미노기에서 Z 기를 수반하며, 여기서
Z는 하기 화학식의 기이다:
(여기서, R은 C18 직쇄 알킬렌기이고;
R1은 CO2H임).
도면은 또한 상기 논의된 바와 같은 본 발명의 예시 펩티드를 사용한 생체내 섭식 효력 연구의 결과를 요약한다.
섭식 점수를 나타내는 열의 오른쪽에 있는 도면은 중국 햄스터 난소(CHO) 세포에서 과발현된 GLP-1 수용체의 펩티드와 같은 수용체 효능 데이터를 나타낸다. 생물학적 활성은 상기 기재된 바와 같이 CHO 세포에서 cAMP 생성을 자극하는 펩티드의 효능에 의해 평가되었다.
도면에서 알 수 있는 바와 같이, 음식에 자유롭게 접근하고 본 발명의 예시 펩티드가 투여된 래트는, 식염수를 투여받은 래트에 비해 감소된 체중 증가를 달성하거나 체중 감소를 달성했다. 이는 본 발명의 화합물이 대사 개선에 특히 효과적이며 비만과 같은 장애의 치료에 사용된다는 것을 뒷받침한다. 그러나, 예시 펩티드를 투여한 래트가 섭취한 음식의 양은 식염수를 투여한 래트가 섭취한 음식의 양과 유사하거나 더 많았다. 음식 섭취량에 미치는 영향이 없거나 최소한의 영향은 화합물이 구토와 관련된 부작용을 감소시켰다는 것을 뒷받침한다. 상기에서 논의된 바와 같이, 설치류는 토할 수는 없지만 구토를 경험하는 설치류는 음식 소비를 미루는 경향이 있다. 본 발명의 펩티드를 사용하면 동물이 음식 섭취를 미루는 증거가 관찰되지 않았다.
반감기:
본 발명의 선택된 화합물의 반감기를 측정하였다. 결과는 시간 단위로 도 1 내지 도 1bm의 표의 맨 오른쪽에 있는 t½ 열에 나타나 있다.
전술한 설명에서, 공지된, 명백하거나 예측 가능한 등가물을 갖는 정수 또는 요소가 언급되는 경우, 이러한 등가물은 마치 개별적으로 제시된 것처럼 본 명세서에 포함된다. 본 발명의 진정한 범주를 결정하기 위한 청구범위를 참조해야 하며, 이는 임의의 그러한 등가물을 포함하도록 해석되어야 한다. 또한, 바람직한, 유리한, 편리한 등으로서 기술되는 본 발명의 정수 또는 특징이 선택적이며 독립항의 범주를 제한하지 않는다는 것이 독자에 의해 이해될 것이다. 더욱이, 그러한 선택적인 정수 또는 특징은, 본 발명의 일부 실시형태에서 가능한 이점이 있지만 바람직하지 않을 수 있고 따라서 다른 실시형태에서는 없을 수 있음을 이해해야 한다.
<110> Imperial College Innovations Limited
<120> Novel compounds
<130> P031706WO
<160> 536
<170> PatentIn version 3.5
<210> 1
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 1
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
15 19 24 29
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
34 39 44
Ser Gly Ala Pro Pro Pro Lys
49
<210> 2
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 2
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 3
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 3
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 4
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 4
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 5
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 5
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 6
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 6
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 7
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 7
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 8
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 8
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 9
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 9
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 10
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 10
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 11
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 11
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 12
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 12
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 13
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 13
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 14
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 14
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 15
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 15
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 16
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 16
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 17
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 17
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
His Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 18
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 18
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 19
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 19
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 20
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 20
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 21
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 21
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 22
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 22
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 23
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 23
Phe Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 24
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 24
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 25
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 25
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys
35
<210> 26
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 26
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly Ala Pro Pro Pro Lys
35
<210> 27
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 27
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 28
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 28
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 29
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 29
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 30
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 30
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 31
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 31
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 32
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 32
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 33
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 33
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 34
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 34
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 35
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 35
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 36
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 36
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 37
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 37
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 38
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 38
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 39
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 39
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 40
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 40
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 41
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 41
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 42
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 42
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 43
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 43
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Lys
35
<210> 44
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 44
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 45
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 45
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 46
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 46
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 47
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 47
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 48
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 48
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 49
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 49
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 50
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 50
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Gly Lys
35
<210> 51
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 51
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Gly Lys
35
<210> 52
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 52
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 53
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 53
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Gly Lys
35
<210> 54
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 54
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 55
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 55
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 56
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 56
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 57
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 57
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 58
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 58
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 59
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 59
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 60
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 60
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 61
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 61
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 62
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 62
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 63
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 63
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 64
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 64
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 65
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 65
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Pro Pro Pro Gly Lys
35
<210> 66
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 66
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 67
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 67
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 68
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 68
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 69
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 69
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 70
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 70
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 71
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 71
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 72
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 72
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 73
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 73
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 74
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y2 group
attached to its epsilon amino group
<400> 74
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 75
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 75
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 76
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 76
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 77
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 77
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys
35
<210> 78
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 78
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 79
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 79
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 80
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 80
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 81
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 81
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 82
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 82
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 83
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 83
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 84
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 84
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 85
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 85
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 86
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 86
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 87
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 87
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 88
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 88
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 89
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 89
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 90
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 90
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 91
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 91
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 92
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 92
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 93
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 93
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 94
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 94
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 95
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 95
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 96
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 96
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 97
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 97
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 98
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 98
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 99
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 99
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 100
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 100
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 101
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 101
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 102
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 102
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 103
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 103
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 104
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 104
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 105
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 105
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Gln Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 106
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 106
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 107
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 107
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 108
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 108
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 109
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 109
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 110
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 110
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 111
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 111
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 112
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 112
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 113
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 113
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 114
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 114
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 115
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 115
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 116
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 116
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 117
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 117
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 118
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 118
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 119
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 119
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 120
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 120
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 121
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 121
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 122
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 122
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 123
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 123
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 124
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 124
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 125
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 125
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 126
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 126
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 127
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 127
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 128
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 128
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 129
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 129
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 130
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 130
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 131
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 131
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 132
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 132
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 133
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 133
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 134
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 134
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 135
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 135
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 136
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 136
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 137
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 137
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 138
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 138
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 139
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 139
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 140
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 140
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 141
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 141
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 142
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 142
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 143
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 143
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 144
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 144
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 145
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 145
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 146
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 146
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 147
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 147
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Gly Lys
35
<210> 148
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 148
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Gly Lys
35
<210> 149
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 149
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 150
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 150
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 151
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 151
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 152
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 152
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 153
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 153
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Gly Lys
35
<210> 154
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 154
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Gly Lys
35
<210> 155
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 155
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 156
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 156
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Arg Pro Pro Pro Lys Lys
35 40
<210> 157
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 157
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Arg Pro Pro Pro Gly Lys
35 40
<210> 158
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 158
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 159
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 159
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 160
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 160
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 161
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 161
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 162
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 162
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 163
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 163
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 164
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 164
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 165
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 165
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 166
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 166
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 167
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 167
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 168
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 168
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 169
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 169
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 170
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 170
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 171
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 171
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 172
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 172
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 173
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 173
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 174
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 174
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 175
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 175
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Lys Lys
35 40
<210> 176
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 176
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 177
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 177
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 178
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 178
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 179
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 179
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 180
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 180
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys Lys
35 40
<210> 181
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 181
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 182
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 182
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 183
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 183
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 184
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 184
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 185
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 185
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 186
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 186
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 187
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 187
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 188
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 188
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 189
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 189
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 190
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 190
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 191
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 191
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 192
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 192
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 193
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 193
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 194
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 194
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 195
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 195
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 196
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 196
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 197
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 197
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 198
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 198
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 199
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 199
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 200
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 200
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 201
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 201
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 202
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 202
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 203
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 203
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 204
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 204
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 205
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 205
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 206
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 206
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 207
<211> 39
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (39)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 207
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys
35
<210> 208
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 208
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 209
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 209
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 210
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 210
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 211
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 211
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 212
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 212
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 213
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 213
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 214
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 214
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 215
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 215
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 216
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 216
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 217
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 217
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 218
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 218
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 219
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 219
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 220
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 220
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 221
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 221
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 222
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 222
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 223
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 223
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 224
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 224
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 225
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 225
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 226
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 226
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 227
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 227
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 228
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 228
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 229
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 229
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 230
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 230
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 231
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 231
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 232
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 232
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 233
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 233
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Lys Lys
35 40
<210> 234
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 234
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 235
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 235
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 236
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 236
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 237
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 237
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 238
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 238
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Lys Lys
35 40
<210> 239
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 239
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 240
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 240
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys
35 40
<210> 241
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 241
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 242
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 242
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 243
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 243
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 244
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 244
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 245
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 245
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 246
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 246
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 247
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 247
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 248
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 248
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 249
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 249
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 250
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 250
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 251
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 251
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 252
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 252
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 253
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 253
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 254
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 254
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 255
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 255
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 256
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 256
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 257
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 257
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 258
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 258
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 259
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 259
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 260
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 260
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 261
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 261
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 262
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 262
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 263
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 263
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 264
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 264
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 265
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 265
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 266
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 266
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 267
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 267
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Gln Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 268
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 268
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 269
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 269
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 270
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 270
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 271
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 271
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 272
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 272
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 273
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 273
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 274
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 274
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 275
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 275
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 276
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 276
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 277
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 277
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 278
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 278
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 279
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 279
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His His Pro Pro Pro Gly Lys
35 40
<210> 280
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 280
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 281
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 281
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 282
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 282
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 283
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 283
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 284
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 284
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 285
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 285
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 286
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 286
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 287
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 287
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 288
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 288
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 289
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 289
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 290
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 290
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 291
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 291
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 292
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 292
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys
35 40
<210> 293
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 293
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 294
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 294
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 295
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 295
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 296
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 296
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 297
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 297
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 298
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 298
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 299
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 299
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 300
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 300
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 301
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 301
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 302
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 302
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 303
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 303
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 304
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 304
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 305
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 305
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Gly Lys
35 40
<210> 306
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 306
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 307
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 307
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys
35 40
<210> 308
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 308
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 309
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 309
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 310
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 310
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 311
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 311
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 312
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 312
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 313
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 313
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 314
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 314
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 315
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 315
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 316
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 316
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
His Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 317
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 317
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 318
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 318
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 319
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 319
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 320
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 320
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 321
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 321
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 322
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 322
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 323
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 323
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 324
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 324
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 325
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 325
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 326
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 326
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 327
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 327
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 328
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 328
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 329
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 329
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 330
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 330
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 331
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 331
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 332
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 332
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 333
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 333
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 334
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 334
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 335
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 335
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 336
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 336
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 337
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 337
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 338
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 338
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 339
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 339
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 340
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 340
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 341
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 341
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 342
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 342
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 343
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 343
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Lys His Pro Pro Pro Gly Lys Lys
35 40
<210> 344
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 344
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His His Pro Pro Pro Gly Lys Lys
35 40
<210> 345
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 345
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 346
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 346
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly His Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 347
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 347
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 348
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 348
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 349
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 349
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 350
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 350
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 351
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 351
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 352
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 352
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 353
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 353
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 354
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 354
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 355
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 355
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 356
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 356
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 357
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 357
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 358
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 358
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 359
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 359
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val His Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 360
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 360
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 361
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 361
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 362
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 362
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 363
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 363
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 364
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 364
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 365
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 365
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 366
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 366
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 367
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 367
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 368
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 368
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Lys Lys
35 40
<210> 369
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 369
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 370
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 370
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 371
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 371
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Lys Lys
35 40
<210> 372
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 372
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Leu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 373
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 373
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 374
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 374
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 375
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 375
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 376
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 376
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 377
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 377
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 378
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 378
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 379
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 379
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys
35 40
<210> 380
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 380
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 381
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 381
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 382
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 382
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys
35 40
<210> 383
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 383
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys
35 40
<210> 384
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 384
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys
35 40
<210> 385
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 385
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 386
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 386
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys
35 40
<210> 387
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 387
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 388
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 388
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 389
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 389
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 390
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 390
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 391
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 391
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 392
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 392
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 393
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 393
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 394
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 394
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 395
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 395
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 396
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 396
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 397
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 397
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 398
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 398
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 399
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 399
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Lys Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 400
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 400
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 401
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 401
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 402
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 402
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 403
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 403
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 404
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 404
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val His Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 405
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 405
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Lys Lys
35 40
<210> 406
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 406
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Lys Lys
35 40
<210> 407
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 407
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Lys Lys
35 40
<210> 408
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 408
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
His Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 409
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 409
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 410
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 410
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 411
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 411
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Lys Lys
35 40
<210> 412
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 412
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Lys Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 413
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 413
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 414
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 414
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 415
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 415
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 416
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (40)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 416
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys
35 40
<210> 417
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 417
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 418
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 418
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln His Pro Pro Pro Gly Lys Lys
35 40
<210> 419
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 419
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 420
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 420
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 421
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 421
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Phe Pro Pro Pro Gly Lys Lys
35 40
<210> 422
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 422
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Phe Pro Pro Pro Gly Lys Lys
35 40
<210> 423
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 423
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Phe Pro Pro Gly Lys Lys
35 40
<210> 424
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 424
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Gln Pro Pro Gly Lys Lys
35 40
<210> 425
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 425
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Pro Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 426
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 426
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Ser Pro Pro Pro Gly Lys Lys
35 40
<210> 427
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 427
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Gln Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 428
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 428
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 429
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 429
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 430
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 430
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 431
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 431
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 432
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 432
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 433
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 433
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Glu Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 434
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 434
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 435
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 435
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 436
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 436
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 437
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 437
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Arg Pro Pro Gly Lys Lys
35 40
<210> 438
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 438
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 439
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 439
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Arg Pro Pro Pro Gly Lys Lys
35 40
<210> 440
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 440
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Arg Pro Pro Pro Gly Lys Lys
35 40
<210> 441
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 441
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 442
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 442
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 443
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 443
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 444
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 444
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Asn Ala Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 445
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 445
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 446
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 446
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 447
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 447
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 448
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 448
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 449
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 449
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 450
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 450
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 451
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 451
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 452
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 452
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 453
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 453
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 454
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 454
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 455
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 455
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 456
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 456
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 457
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 457
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 458
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 458
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 459
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 459
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 460
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 460
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 461
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 461
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 462
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 462
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys His Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 463
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 463
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 464
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 464
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Asn Pro Pro Pro Gly Lys Lys
35 40
<210> 465
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 465
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 466
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 466
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 467
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 467
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 468
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 468
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 469
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 469
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 470
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 470
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 471
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 471
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 472
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 472
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 473
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 473
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 474
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 474
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 475
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 475
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 476
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 476
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly His Pro Pro Pro Gly Lys Lys
35 40
<210> 477
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 477
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 478
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 478
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 479
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 479
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 480
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 480
His Xaa His Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val His Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 481
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 481
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 482
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 482
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 483
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 483
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 484
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 484
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 485
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 485
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 486
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 486
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 487
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 487
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 488
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 488
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Gly Lys Lys
35 40
<210> 489
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 489
His Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 490
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 490
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 491
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 491
Tyr Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 492
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 492
Phe Xaa His Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 493
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 493
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 494
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 494
Tyr Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 495
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 495
Phe Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 496
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 496
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 497
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 497
His Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 498
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 498
Tyr Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 499
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 499
Phe Xaa His Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 500
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 500
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 501
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 501
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 502
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 502
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 503
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 503
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 504
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 504
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 505
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 505
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 506
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 506
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 507
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 507
His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 508
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 508
His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 509
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 509
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 510
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 510
His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 511
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 511
His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 512
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 512
Phe Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 513
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 513
Phe Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 514
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 514
His Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 515
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 515
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 516
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 516
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 517
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 517
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 518
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 518
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 519
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 519
His Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 520
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 520
His Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 521
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 521
His Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Ala Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 522
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 522
His Xaa Gln Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 523
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 523
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 524
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 524
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 525
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 525
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Glu Pro Pro Pro Gly Lys Lys
35 40
<210> 526
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 526
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Gln Pro Pro Pro Gly Lys Lys
35 40
<210> 527
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> MOD_RES
<222> (41)
<223> The residue at this position is Lys modified with a Y group
attached to its epsilon amino group
<400> 527
Phe Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Lys Gln Leu Glu Glu
1 5 10 15
Lys Arg Val Arg Glu Phe Ile Glu Trp Leu Lys Gln Gly Gly Pro Ser
20 25 30
Ser Gly Lys Pro Pro Pro Gly Lys Lys
35 40
<210> 528
<211> 42
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<220>
<221> VARIANT
<222> (1)
<223> The residue at this position is His, Tyr or Phe
<220>
<221> MOD_RES
<222> (2)
<223> Aib
<220>
<221> VARIANT
<222> (3)
<223> The residue at this position is His, Gln or Glu
<220>
<221> VARIANT
<222> (10)
<223> The residue at this position is Leu, Tyr or Val
<220>
<221> VARIANT
<222> (17)
<223> The residue at this position is Glu or Lys
<220>
<221> VARIANT
<222> (18)
<223> The residue at this position is Ala or Arg
<220>
<221> VARIANT
<222> (20)
<223> The residue at this position is Arg, Gln, Lys or His
<220>
<221> VARIANT
<222> (21)
<223> The residue at this position is Leu, Ala, Arg, Lys or Glu
<220>
<221> VARIANT
<222> (28)
<223> The residue at this position is Ala, Asn, Gln, His
<220>
<221> VARIANT
<222> (29)
<223> The residue at this position is Gly or Ala
<220>
<221> VARIANT
<222> (33)
<223> The residue at this position is Ser, His or Gln
<220>
<221> VARIANT
<222> (35)
<223> The residue at this position is Lys, Pro, His, Arg, Asn, Gln,
Glu, Ser or Ala
<220>
<221> VARIANT
<222> (36)
<223> The residue at this position is Phe, His, Gln, Glu, Lys, Ser, Arg
or absent
<220>
<221> VARIANT
<222> (39)
<223> The residue at this position is Pro or Gly
<220>
<221> VARIANT
<222> (40)
<223> The residue at this position is Gly or absent
<220>
<221> VARIANT
<222> (41)
<223> The residue at this position is Lys or absent
<220>
<221> MOD_RES
<222> (42)
<223> The residue at this position is Lys modified with a Y2 group
attached to its epsilon amino group
<400> 528
Xaa Xaa Xaa Gly Thr Phe Thr Ser Asp Xaa Ser Lys Gln Leu Glu Glu
1 5 10 15
Xaa Xaa Val Xaa Xaa Phe Ile Glu Trp Leu Lys Xaa Xaa Gly Pro Ser
20 25 30
Xaa Gly Xaa Xaa Pro Pro Xaa Xaa Xaa Lys
35 40
<210> 529
<211> 31
<212> PRT
<213> Homo sapiens
<400> 529
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly
20 25 30
<210> 530
<211> 30
<212> PRT
<213> Homo sapiens
<220>
<221> MOD_RES
<222> (30)
<223> AMIDATION
<400> 530
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
20 25 30
<210> 531
<211> 29
<212> PRT
<213> Homo sapiens
<400> 531
His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser
1 5 10 15
Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr
20 25
<210> 532
<211> 37
<212> PRT
<213> Homo sapiens
<400> 532
His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser
1 5 10 15
Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Lys Arg Asn
20 25 30
Arg Asn Asn Ile Ala
35
<210> 533
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<400> 533
Pro Pro Pro Gly Lys
15 19
<210> 534
<211> 4
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<400> 534
Pro Pro Pro Lys
1
<210> 535
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<400> 535
Asp Asp Asp Asp Tyr
15 19
<210> 536
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Component of peptide hormone analogue
<400> 536
His Pro Phe His Leu
15 19
Claims (18)
- 식 (I)의 아미노산 서열을 갖는 화합물 또는 화합물의 유도체; 화합물 또는 유도체의 염 또는 용매화물:
Xaa1 - AIB2- Xaa3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Xaa10-Ser11- Lys12- Gln13-Leu14- Glu15- Glu16-Xaa17-Xaa18-Val19-Xaa20-Xaa21 -Phe22- Ile23- Glu24-Trp25- Leu26- Lys27-Xaa28-Xaa29-Gly30-Pro31 -Ser32-Xaa33-Gly34-Xaa35-Xaa36- Pro37-Pro38-Xaa39-Xaa40-Xaa41 -Lys42; (I) [서열 번호 528]
상기 식에서,
Xaa1은 His, Tyr 또는 Phe이고;
Xaa3은 His, Gln 또는 Glu이고;
Xaa10은 Leu, Tyr 또는 Val이고;
Xaa17은 Glu 또는 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg, Gln, Lys 또는 His이고;
Xaa21은 Leu, Ala, Arg, Lys 또는 Glu이고;
Xaa28은 Ala, Asn, Gln, His이고;
Xaa29는 Gly 또는 Ala이고;
Xaa33은 Ser, His 또는 Gln이고;
Xaa35는 Lys, Pro, His, Arg, Asn, Gln, Glu, Ser 또는 Ala이고;
Xaa36은 Phe, His, Gln, Glu, Lys, Ser, Arg이거나 부재하고;
Xaa39는 Pro 또는 Gly이고;
Xaa40은 Gly이거나 부재하고;
Xaa41은 Lys이거나 또는 부재하고;
위치 42에서의 라이신 잔기는 그의 ε-아미노기에서 기 Y로 치환되고, Y는
Z-Xaa43-Xaa44-이고, 여기서,
Xaa43은 Asn이거나 부재하고;
Xaa44는 His이거나 부재하고;
Z는 하기 화학식의 기이다:
(여기서, R은 C16-C18 알킬렌 또는 알케닐렌 기이고;
R1은 CO2H임). - 제1항에 있어서,
Xaa17은 Lys이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Leu 또는 Glu이고;
Xaa28은 Ala, Gln 또는 His이고;
Xaa29는 Gly이고;
Xaa33은 Ser이고;
Xaa35는 Lys, Glu, His, Gln 또는 Asn이고;
Xaa36은 부재하고;
Xaa39는 Pro이고;
Xaa41은 Lys이고;
Xaa43은 부재하고;
Xaa44는 부재하고;
R은 C18 알킬렌 기인, 화합물, 유도체, 염 또는 용매화물. - 제2항에 있어서,
Xaa1은 His 또는 Phe이고;
Xaa3은 His 또는 Glu이고;
Xaa10은 Tyr 또는 Val이고;
Xaa17은 Lys이고;
Xaa18은 Ala 또는 Arg이고;
Xaa20은 Arg 또는 His이고;
Xaa21은 Glu이고;
Xaa28은 Ala 또는 Gln이고;
Xaa35는 Lys이고;
Xaa40은 Gly인, 화합물, 유도체, 염 또는 용매화물. - 제1항에 있어서, 도 1 내지 도 1bm의 표에 열거된 아미노산 서열 중 어느 하나에 상응하는 아미노산 서열을 갖는, 화합물, 유도체, 염 또는 용매화물.
- 제1항 내지 제4항 중 어느 한 항에 있어서, 아미드화, 글리코실화, 카르바밀화, 아실화, 황산화, 인산화, 고리화, 지질화, 페길화, 및 융합 단백질을 형성하기 위한 또 다른 펩티드 또는 단백질에 대한 융합으로부터 선택되는 하나 이상의 유도체화를 포함하는, 화합물의 유도체, 또는 이러한 유도체의 염 또는 용매화물.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 추가의 치료제와 함께, 동시, 순차적 또는 별도의 투여를 위한, 화합물, 유도체, 염 또는 용매화물.
- 약제학적으로 허용가능한 담체 및 선택적으로 추가의 치료제와 함께, 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물을 포함하는 조성물.
- 제7항에 있어서, 인간에게 피하 투여하기 위한 주사기 또는 다른 투여 장치에 존재하는, 조성물.
- 약제로서 사용하기 위한, 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물, 또는 제7항 또는 제8항에 기재된 조성물.
- 치료적 유효량의 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물, 또는 제7항 또는 제8항에 기재된 조성물을 투여하는 단계를 포함하는, 대상체에서 질환 또는 장애 또는 다른 원치 않는 생리학적 상태를 치료 또는 예방하는 방법.
- 당뇨병, 비만, 심장 질환, 뇌졸중 또는 비-알코올성 지방간 질환을 예방 또는 치료하고, 대상체에서 인슐린 방출을 개선하고, 대상체에서 탄수화물 대사를 개선하고, 대상체에서 지질 프로파일을 개선하고, 대상체에서 식욕을 감소시키고, 음식 섭취량을 감소시키고, 칼로리 섭취를 감소시키고, 탄수화물 내성을 개선하는 데 사용하기 위한, 및/또는 세포보호제로서 사용하기 위한, 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물, 또는 제7항 또는 제8항에 기재된 약제학적 조성물.
- 제11항에 있어서, 화합물, 유도체, 염 또는 조성물은 신경퇴행의 예방 또는 치료, 신경보호 제공 및/또는 심장 보호 제공에 사용하기 위한 것인, 세포보호제로서 사용하기 위한 화합물, 유도체, 염 또는 용매화물 또는 조성물.
- 제12항에 있어서, 화합물, 유도체, 염 또는 조성물은 심근 경색 후 대상체에서 심장 보호를 제공하기 위한 것인, 세포보호제로서 사용하기 위한 화합물, 유도체, 염 또는 용매화물 또는 조성물.
- 제12항에 있어서, 화합물, 유도체, 염 또는 조성물은 만성 신경퇴행성 질환을 갖거나 위험이 있는 것으로 진단된 대상체에서 신경보호를 제공하기 위한 것인, 세포보호제로서 사용하기 위한 화합물, 유도체, 염 또는 용매화물 또는 조성물.
- 제14항에 있어서, 만성 신경퇴행성 질환은 알츠하이머병, 파킨슨병, 게릭병(근위축성 측색 경화증), 헌팅턴병, 다발성 경화증, 기타 탈수초 관련 장애, 노인성 치매, 피질하 치매, 동맥경화성 치매, AIDS 관련 치매, 기타 치매, 뇌혈관염, 간질, 뚜렛 증후군, 길랭 바레 증후군, 윌슨병, 피크병, 신경염증성 질환, 뇌염, 뇌척수염, 수막염, 기타 중추신경계 감염, 프리온 질환, 소뇌 운동실조, 소뇌 변성, 척수소뇌 변성 증후군, 프리드리히 운동실조, 모세혈관 확장성 운동실조(ataxia teangiectasia), 척수 근위축증, 진행성 핵상 마비, 근육긴장이상, 근육 경직, 떨림, 색소성 망막염, 선조체 흑질 변성, 미토콘드리아 뇌근병증 및 신경원세로이드 리포푸신증으로 이루어진 군으로부터 선택되는, 화합물, 유도체, 염 또는 용매화물 또는 조성물.
- 치료적 유효량의 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물, 또는 제7항 또는 제8항에 기재된 조성물을 투여하는 단계를 포함하는, 대상체에서 당뇨병, 비만, 심장 질환, 뇌졸중 또는 비-알코올성 지방간 질환을 예방 또는 치료하고/하거나, 대상체에서 인슐린 방출을 개선하고/하거나, 대상체에서 탄수화물 대사를 개선하고/하거나, 대상체에서 지질 프로파일을 개선하고/하거나, 대상체에서 탄수화물 내성을 개선하고/하거나, 대상체에서 식욕을 감소시키고/시키거나, 음식 섭취량을 감소시키고/시키거나, 칼로리 섭취를 감소시키고/시키거나, 세포보호를 제공하는 방법.
- 당뇨병, 비만, 심장 질환, 뇌졸중 및 비-알코올성 지방간 질환을 예방 또는 치료하고/하거나, 대상체에서 인슐린 방출을 개선하고/하거나, 대상체에서 탄수화물 대사를 개선하고/하거나, 대상체에서 지질 프로파일을 개선하고/하거나, 대상체에서 탄수화물 내성을 개선하고/하거나, 식욕을 감소시키고/시키거나, 칼로리 섭취를 감소시키고/시키기 위한, 및/또는 세포보호제로서 사용하기 위한 약제의 제조를 위한, 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물의 용도.
- 유효량의 제1항 내지 제6항 중 어느 한 항에 기재된 화합물, 유도체, 염 또는 용매화물, 또는 제7항 또는 제8항에 기재된 조성물을 투여하는 단계를 포함하는, 미용 목적을 위해 대상체에서 체중 감소를 유발하거나 체중 증가를 방지하는 방법.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB2019588.9 | 2020-12-11 | ||
GBGB2019588.9A GB202019588D0 (en) | 2020-12-11 | 2020-12-11 | Novel Compounds |
GB2110809.7 | 2021-07-27 | ||
GBGB2110809.7A GB202110809D0 (en) | 2021-07-27 | 2021-07-27 | Novel compounds |
PCT/GB2021/053249 WO2022123271A1 (en) | 2020-12-11 | 2021-12-10 | Novel compounds |
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US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
CA1257199A (en) | 1986-05-20 | 1989-07-11 | Paul Y. Wang | Preparation containing bioactive macromolecular substance for multi-months release in vivo |
IT1243390B (it) | 1990-11-22 | 1994-06-10 | Vectorpharma Int | Composizioni farmaceutiche in forma di particelle atte al rilascio controllato di sostanze farmacologicamente attive e procedimento per la loro preparazione. |
US5907030A (en) | 1995-01-25 | 1999-05-25 | University Of Southern California | Method and compositions for lipidization of hydrophilic molecules |
US6093692A (en) | 1997-09-25 | 2000-07-25 | The University Of Southern California | Method and compositions for lipidization of hydrophilic molecules |
FR2774674B1 (fr) | 1998-02-10 | 2000-03-24 | Atochem Elf Sa | Procede de preparation d'une solution aqueuse de peroxyde d'hydrogene directement a partir d'hydrogene et d'oxygene et dispositif permettant sa mise en oeuvre |
US5993414A (en) | 1998-04-23 | 1999-11-30 | Medtronic, Inc. | Implantable device |
EP1076066A1 (en) * | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
US6436091B1 (en) | 1999-11-16 | 2002-08-20 | Microsolutions, Inc. | Methods and implantable devices and systems for long term delivery of a pharmaceutical agent |
WO2005021022A2 (en) * | 2003-09-01 | 2005-03-10 | Novo Nordisk A/S | Stable formulations of peptides |
WO2006097538A1 (en) * | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Extended glp-1 compounds |
US20090098130A1 (en) * | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
EP2200626A4 (en) * | 2007-09-07 | 2012-02-15 | Ipsen Pharma Sas | ANALOGUE OF EXENDIN-4 AND EXENDIN-3 |
US8642544B2 (en) * | 2009-04-01 | 2014-02-04 | Amylin Pharmaceuticals, Llc | N-terminus conformationally constrained GLP-1 receptor agonist compounds |
MX343360B (es) * | 2010-04-27 | 2016-11-03 | Zealand Pharma As | Conjugados peptidicos de agonistas del receptor de glp-1 y gastrina y su uso. |
WO2013004983A1 (en) | 2011-07-04 | 2013-01-10 | Imperial Innovations Limited | Novel compounds and their effects on feeding behaviour |
GB201404002D0 (en) | 2014-03-06 | 2014-04-23 | Imp Innovations Ltd | Novel compounds |
CN104211801A (zh) * | 2014-07-25 | 2014-12-17 | 杭州诺泰制药技术有限公司 | 一种制备利西拉来的方法 |
WO2017178829A1 (en) | 2016-04-15 | 2017-10-19 | Imperial Innovations Limited | Peptide analogues |
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CA3199733A1 (en) | 2022-06-16 |
WO2022123271A1 (en) | 2022-06-16 |
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GB2616205A (en) | 2023-08-30 |
AU2021397877A1 (en) | 2023-07-06 |
IL303549A (en) | 2023-08-01 |
EP4259646A1 (en) | 2023-10-18 |
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