KR20150013339A - 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도 - Google Patents

인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도 Download PDF

Info

Publication number
KR20150013339A
KR20150013339A KR1020147036380A KR20147036380A KR20150013339A KR 20150013339 A KR20150013339 A KR 20150013339A KR 1020147036380 A KR1020147036380 A KR 1020147036380A KR 20147036380 A KR20147036380 A KR 20147036380A KR 20150013339 A KR20150013339 A KR 20150013339A
Authority
KR
South Korea
Prior art keywords
arg
cys
seq
ala
trp
Prior art date
Application number
KR1020147036380A
Other languages
English (en)
Inventor
헤더 에이. 할렘
마이클 드윗 쿨러
앤드류 에이. 버틀러
Original Assignee
입센 파마 에스.에이.에스
보드 오브 슈퍼바이저스 오브 루이지애나 스테이트 유니버시티 앤드 애그리컬추얼 앤드 메카니컬 컬리지
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 입센 파마 에스.에이.에스, 보드 오브 슈퍼바이저스 오브 루이지애나 스테이트 유니버시티 앤드 애그리컬추얼 앤드 메카니컬 컬리지 filed Critical 입센 파마 에스.에이.에스
Publication of KR20150013339A publication Critical patent/KR20150013339A/ko

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links

Abstract

본 발명은 인슐린 내성과 같이 멜라노코르틴 수용체의 활성화에 반응하는 질병의 치료에 유용한, 멜라노코르틴 수용체, 특히 멜라노코르틴-4 수용체에 대한 펩타이드 리간드에 관한 것이다.

Description

인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도{USE MELANOCORTINS TO TREAT INSULIN SENSITIVITY}
멜라노코르틴은 프로호르몬인 프로-오피오멜라노코르틴(POMC; 131개의 아미노산 길이)의 번역후 가공에 의해 생성되는 조절 펩타이드 계열이다. POMC는 3가지 클래스의 호르몬으로 가공된다: 멜라노코르틴, 아드레노코르티코트로핀 호르몬 및 다양한 엔도르핀(예, 리포트로핀)(Cone et al., Recent Prog. Horm. Res., 51:287-317, (1996); Cone et al., Ann. N.Y. Acad. Sci., 31:342-363, (1993)).
지금까지 5종의 멜라노코르틴 수용체(MC-R)가 규명되었다. 이들은, 멜라노사이트-특이적인 수용체(MC1-R), 코르티코아드레날-특이적인 ACTH 수용체(MC2-R), 멜라노코르틴-3(MC3-R), 멜라노코르틴-4(MC4-R) 및 멜라노코르틴-5 수용체(MC5-R) 등이다. 이들 멜라노코르틴 수용체들 모두 멜라노사이트 자극 호르몬(MSH)계 펩타이드 호르몬에 반응한다(Cone et al., Ann. N.Y. Acad. Sci., 680:342-363 (1993); Cone et al., Recent Prog. Horm. Res., 51:287-318 (1996)).
멜라노코르틴(MC-R) 수용체는 비만 및 악액질과 같은 체중 장애를 치료하기 위한 새로운 치료제를 설계함에 있어 표적으로서 큰 주목을 받고 있다. 수용체들 중에서도, MC4-R은 태반과 장 뿐만 아니라 뇌에서도 발현되는 332개의 아미노산으로 이루어진 트랜스멤브레인 단백질이다(Cone et al., Ann. N.Y. Acad. Sci., 680:342-363 (1993); Cone et al., Recent Prog. Horm. Res., 51:287-318 (1996)). 최근 중추 MC4-수용체가 멜라노코르틴 작용제 및 길항제 각각에 대해 보고된 식욕 부진 및 식욕 촉진의 주요 매개체임이 약학적으로 확인되었다(Giraudo et al., Brain Res., 809:302-306 (1998); Farooqi et al., NE J Med., 348:1085-1095 (2003); MacNeil et al., Eu. J. Pharm., 44:141-157 (2002); MacNeil et al., Eu. J. Pharm., 450:93-109 (2002); Kask et al., NeuroReport, 10:707-711 (1999); Chen et al.,. Transgenic Res., 9:145-54, (2000); Marsh et al., Nat Genet., 21:119-22, (1999); Balthasar et al., Cell, 123:493-505 (2005)).
통상적으로 체중 장애 합병증은 흔히 글루코스 조절에 결함을 초래하는, 인슐린 생산 및 이용 불능을 포함한다. 적절한 글루코스 대사 조절 실패는 에너지 대사, 신경증 및 심장병 등의 여러가지 전반적인 건강 측면에 영향을 미칠 수 있다. 현재 수용체-선택적인 멜라노코르틴 수용체 리간드에 대한 연구의 진행으로, 멜라노코르틴 수용체, 특히 MC4-R의 활성화가 인슐린 대사 등의 글루코스 조절 치료에 치료학적 가능성이 있다는 것이 입증되었다.
본 발명은, 1종 이상의 멜라노코르틴 수용체(MC-R)의 리간드인 펩타이드, 또는 그것의 약학적으로 허용가능한 염의, 인슐린 내성을 앓고 있는 포유류를 치료함에 있어서의 용도에 관한 것이다.
발명의 개요
본 발명은, 1종 이상의 멜라노코르틴 수용체(MC-R)의 리간드인 펩타이드, 또는 그것의 약학적으로 허용가능한 염의, 인슐린 내성을 앓고 있는 포유류를 치료함에 있어서의 용도에 관한 것이다. 일 구현예에서, 상기 리간드는 멜라노코르틴 4 수용체에 대해 작용제이다. 바람직한 구현예에서, 멜라노코르틴 수용체 리간드는 본원에 기술된 식으로 표시되거나, 또는 본원에 기술된 특정 펩타이드들 중에서 선택된다.
인슐린 내성을 가진 대상 포유류는 비만 또는 과체중일 수 있으며, 본 발명의 펩타이드를 복용함으로써 체중이 감소될 수 있다. 또한, 인슐린 내성을 가진 대상 포유류는 정상 체중이거나 저체중일 수도 있다. 상기 대상 포유류의 인슐린 내성 증상은 체중 감소와는 별개로 치료될 수 있다. 아울러, 대상 포유류는 유아, 어린이, 성인 또는 노인 등의 모든 연령의 인간 개체일 수 있다.
제1 구현예에서, 본 발명은 식 (I)에 따른 멜라노코르틴 수용체 4 리간드 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 공개번호 WO 2007/008704, 문헌 전체가 원용에 의해 본 발명에 포함됨):
(R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1
(I)
상기 식 (I)에서:
A1은 Acc, HN-(CH2)m-C(O), L- 또는 D-아미노산이거나, 또는 생략되며;
A2는 Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp, 또는 Glu이며;
A3는 Gly, Ala, β-Ala, Gaba, Aib, D-아미노산이거나, 또는 생략되며;
A4는 His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, 또는 (X1,X2,X3,X4,X5)Phe이며;
A5는 D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1,X2,X3,X4,X5)Phe, L-Phe 또는 D-(Et)Tyr이며;
A6은 Arg, hArg, Dab, Dap, Lys, Orn, 또는 HN-CH((CH2)n-N(R4R5))-C(O)이며;
A7은 Trp, 1-Nal, 2-Nal, Bal, Bip, D-Trp, D-1-Nal, D-2-Nal, D-Bal 또는 D-Bip이며;
A8는 Gly, D-Ala, Acc, Ala, b-Ala, Gaba, Apn, Ahx, Aha, HN-(CH2)s-C(O)이거나, 또는 생략되며;
A9는 Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn, 또는 Lys이며;
A10은 Acc, HN-(CH2)t-C(O), L- 또는 D-아미노산이거나, 또는 생략되며;
R1은 OH 또는 NH2이며;
각각의 R2 및 R3는 독립적으로 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C1-C30)아실, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 아릴(C1-C30)아실, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C1-C30)아실, 치환된 (C2-C30)알케닐, 치환된 (C2-C30)알키닐, 치환된 아릴(C1-C30)알킬, 및 치환된 아릴(C1-C30)아실로 이루어진 군으로부터 선택되며;
각각의 R4 및 R5는 독립적으로 H, (C1-C40)알킬, (C1-C40)헤테로알킬, (C1-C40)아실, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 아릴(C1-C40)아실, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C1-C40)아실, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐, 치환된 아릴(C1-C40)알킬, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐, 또는 -C(NH)-NH2이며;
m은 독립적으로 1, 2, 3, 4, 5, 6 또는 7이며;
n는 독립적으로 1, 2, 3, 4 또는 5이며;
s는 독립적으로 1, 2, 3, 4, 5, 6, 또는 7이며;
t는 독립적으로 1, 2, 3, 4, 5, 6, 또는 7이며;
X1, X2, X3, X4 및 X5는 각각 독립적으로 H, F, Cl, Br, I, (C1 -10)알킬, 치환된 (C1 -10)알킬, (C2 -10)알케닐, 치환된 (C2 -10)알케닐, (C2 -10)알키닐, 치환된 (C2 -10)알키닐, 아릴, 치환된 아릴, OH, NH2, NO2, 또는 CN이고,
단,
(I). R4가 (C1-C40)아실, 아릴(C1-C40)아실, 치환된 (C1-C40)아실, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐, 또는 -C(NH)-NH2이면, R5는 H 또는 (C1-C40)알킬, (C1-C40)헤테로알킬, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐, 또는 치환된 아릴(C1-C40)알킬이고;
(II). R2가 (C1-C30)아실, 아릴(C1-C30)아실, 치환된 (C1-C30)아실, 또는 치환된 아릴(C1-C30)아실이면, R3는 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C2-C30)알케닐, 치환된 (C2- C30)알키닐 또는 치환된 아릴(C1-C30)알킬이고;
(III). A3 또는 A8 또는 이들 모두 상기 화합물에 존재하며;
(IV). A2가 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이면, A9는 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이고;
(V). A2가 Asp 또는 Glu이면, A9은 Dab, Dap, Orn 또는 Lys이고;
(VI). A8이 Ala 또는 Gly이면, A1은 Nle이 아니고;
(VII). A1이 생략되면, R2 및 R3는 모두 H가 아니다.
제1 구현예의 일 측면에서, 본 발명은 상기 식 I의 멜라노코르틴 수용체 리간드 서브그룹 또는 그것의 약학적으로 허용가능한 염을 치료학적 유효량으로 투여함으로써 체중 감소를 수반하거나 수반하지 않으면서 포유류 개체에서의 인슐린 내성을 치료하는 방법을 제공하며, 이때,
A1은 A6c, Arg, D-Arg, Cha, D-Cha, hCha, Chg, D-Chg, Gaba, Ile, Leu, hLeu, Met, β-hMet, 2-Nal, D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe, hPro, Val이거나, 또는 생략되며;
A2은 Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, 또는 D-Pen이며;
A3는 D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, D-Glu, Gly, D-Ile, D-Leu, D-Tle, D-Val이거나, 또는 생략되며;
A4는 His 또는 3-Pal이며;
A5는 D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-Trp, 또는 D-(Et)Tyr이며;
A6은 Arg, 또는 hArg이며;
A7은 Bal, Bip, 1-Nal, 2-Nal, Trp, D-Trp이며;
A8은 A6c, D-Ala, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly이거나 생략되며;
A9는 Cys, D-Cys, hCys, D-hCys, Lys, Pen, 또는 D-Pen이며;
A10은 Thr이거나, 또는 생략되며,
A3 또는 A8 중 적어도 하나는 생략되지만, 둘다는 생략되지 않는다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 식 (I)의 리간드 그룹에 대한 보다 바람직한 화합물은 하기 식의 화합물 또는 그것의 약학적으로 허용가능한 염이다:
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; 서열번호 1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; 서열번호 1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; 서열번호 2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; 서열번호 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; 서열번호 3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; 서열번호 4
Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
n-부타노일-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-β -hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; 서열번호 14
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; 서열번호 16
n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 17
n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 17
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 61
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; 서열번호 19
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; 서열번호 20
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 27
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; 서열번호 28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; 서열번호 28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; 서열번호 29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 31
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 37
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; 서열번호 39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; 서열번호 39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; 서열번호 41
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; 서열번호 42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; 서열번호 43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; 서열번호 43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; 서열번호 43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; 서열번호 42
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; 서열번호 41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 29
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; 서열번호 46
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 47
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; 서열번호 29
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; 서열번호 48
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 27
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; 서열번호 1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; 서열번호 2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; 서열번호 3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; 서열번호 4
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; 서열번호 15
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 23
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; 서열번호 28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; 서열번호 28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; 서열번호 29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 31
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 37
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; 서열번호 20
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-b-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; 서열번호 39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; 서열번호 39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40 또는
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 49.
제2 구현예에서, 본 발명은 식 (II)에 따른 멜라노코르틴 수용체 리간드 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 공개번호 WO 2007/008704, 문헌 전체가 원용에 의해 본 발명에 포함됨):
(R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-NH2
(II)
상기 식 (II)에서,
A1은 Nle이거나 생략되며;
A2는 Cys 또는 Asp이며;
A3는 Glu 또는 D-Ala이며;
A4는 His이며;
A5는 D-Phe이며;
A6은 Arg이며;
A7은 Trp, 2-Nal 또는 Bal이며;
A8는 Gly, Ala, D-Ala, b-Ala, Gaba 또는 Apn이며;
A9는 Cys 또는 Lys이며;
각각의 R2 및 R3는 독립적으로 H 또는 (C1-C6)아실로 이루어진 군으로부터 선택되며,
단,
(I). R2가 (C1-C6)아실이면, R3는 H이고;
(II). A2가 Cys이면, A9은 Cys이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 화합물 그룹에 대한 보다 바람직한 화합물은 하기 식의 화합물 또는 그것의 약학적으로 허용가능한 염이다:
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-b-Ala-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 54
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; 서열번호 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 57 또는
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2; 서열번호 58.
제3 구현예에서, 본 발명은 식 (III)에 따른 멜라노코르틴 수용체 리간드 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 공개번호 WO 2007/008684, 문헌 전체가 원용에 의해 본 발명에 포함됨):
(R2R3)-B1-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-A11-A12-A13-B2-B3-R1
(III)
상기 식 (III)에서,
B1은 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 또는 15개의 아미노산을 포함하는 A 펩타이드 모이어티로서, 아미노산 5개 이상은 독립적으로 L-Arg, D-Arg, L-hArg 및 D-hArg로 이루어진 군으로부터 선택되거나, 또는 B1은 선택적으로 생략되며;
A1은 Acc, HN-(CH2)m-C(O), L- 또는 D-아미노산이거나 생략되며;
A2는 Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp 또는 Glu이며;
A3는 Gly, Glu, Ala, β-Ala, Gaba, Aib, D-아미노산이거나 생략되며;
A4는 His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi 또는 (X1,X2,X3,X4,X5)Phe이며;
A5는 D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1,X2,X3,X4,X5)Phe, D-(Et)Tyr, D-Dip, D-Bip 또는 D-Bpa이며;
A6는 Arg, hArg, Dab, Dap, Lys, Orn 또는 HN-CH((CH2)n-N(R4R5))-C(O)이며;
A7은 Trp, 1-Nal, 2-Nal, Bal, Bip, Dip, Bpa, D-Trp, D-1-Nal, D-2-Nal, D-Bal, D-Bip, D-Dip 또는 D-Bpa이며;
A8는 Gly, D-Ala, Acc, Ala, β-Ala, Gaba, Apn, Ahx, Aha, HN-(CH2)s-C(O)이거나 생략되며;
A9는 Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn 또는 Lys이며;
A10은 Acc, HN-(CH2)t-C(O), Pro, hPro, 3-Hyp, 4-Hyp, Thr, L- 또는 D-아미노산이거나 생략되며;
A11은 Pro, hPro, 3-Hyp, 4-Hyp이거나 생략되며;
A12은 Lys, Dab, Dap, Arg, hArg이거나 생략되며;
A13은 Asp, Glu이거나 생략되며;
B2은 1, 2, 3, 4 또는 5개의 아미노산을 포함하는 펩타이드 모이어티이거나 생략되며,
B3은 5개 이상의 아미노산이 독립적으로 L-Arg, D-Arg, L-hArg 및 D-hArg로 이루어진 군으로부터 선택되는, 아미노산 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 또는 15개를 포함하는 펩타이드 모이어티이거나, 또는 생략되며;
R1은 OH 또는 NH2이며;
R2 및 R3는 각각 독립적으로 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C1-C30)아실, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 아릴(C1-C30)아실, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C1-C30)아실, 치환된 (C2-C30)알케닐, 치환된 (C2-C30)알키닐, 치환된 아릴(C1-C30)알킬 및 치환된 아릴(C1-C30)아실로 이루어진 군으로부터 선택되며;
R4 및 R5는 각각 독립적으로 H, (C1-C40)알킬, (C1-C40)헤테로알킬, (C1-C40)아실, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 아릴(C1-C40)아실, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C1-C40)아실, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐, 치환된 아릴(C1-C40)알킬, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐 또는 C(NH)-NH2이며;
n는 독립적으로 1, 2, 3, 4 또는 5이며;
m는 독립적으로 1, 2, 3, 4, 5, 6 또는 7이며;
s는 독립적으로 1, 2, 3, 4, 5, 6 또는 7이며;
t는 독립적으로 1, 2, 3, 4, 5, 6 또는 7이며;
X1, X2, X3, X4 및 X5는 각각 독립적으로 H, F, Cl, Br, I, (C1 -10)알킬, 치환된 (C1 -10)알킬, (C2 -10)알케닐, 치환된 (C2 -10)알케닐, (C2 -10)알키닐, 치환된 (C2 -10)알키닐, 아릴, 치환된 아릴, OH, NH2, NO2 또는 CN이나,
단,
(I) R4가 (C1-C40)아실, 아릴(C1-C40)아실, 치환된 (C1-C40)아실, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐 또는 C(NH)-NH2이면, R5는 H, (C1-C40)알킬, (C1-C40)헤테로알킬, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐 또는 치환된 아릴(C1-C40)알킬이고;
(II)R2가 (C1-C30)아실, 아릴(C1-C30)아실, 치환된 (C1-C30)아실 또는 치환된 아릴(C1-C30)아실이면, R3는 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C2-C30)알케닐, 치환된 (C2-C30)알키닐 또는 치환된 아릴(C1-C30)알킬이고;
(III) B1 또는 B2 둘다 하기 아미노산 서열들 중 하나 이상을 포함하지 않으며: Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Tyr-Ala-Arg-Lys-Ala-(Arg)2-Gln-Ala-(Arg)2, Tyr-Ala-Arg-(Ala)2-(Arg)2-(Ala)2-(Arg)2, Tyr-Ala-(Arg)9, Tyr-(Ala)3-(Arg)7, Tyr-Ala-Arg-Ala-Pro-(Arg)2-Ala-(Arg)3 또는 Tyr-Ala-Arg-Ala-Pro-(Arg)2-Pro-(Arg)2;
(IV)B1, B2 또는 둘다는 상기 화합물에 존재하며;
(V)A2가 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이면, A9은 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이며; 및
(VI)A2가 Asp 또는 Glu이면, A9은 Dab, Dap, Orn 또는 Lys이다.
제3 구현예의 제1 측면에서, 본 발명은 체중 감소를 수반하거나 수반하지 않으면서 포유류 개체에서의 인슐린 내성을 치료하기 위한 상기 식 (III)의 화합물 또는 그것의 약학적으로 허용가능한 염의 사용에 관한 것으로, 이때,
B1은 Arg-Lys-Gln-Lys-(Arg)5, Arg-(Lys)2-Arg-Gln-(Arg)4, Arg-(Lys)2-(Arg)3-Gln-(Arg)2, Arg-(Lys)2-(Arg)4-Gln-Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-(Lys)2-Gln-(Arg)5, Arg-Gln-(Lys)2-(Arg)5, Arg-Gln-(Arg)7, Arg-Gln-(Arg)8, (Arg)2-Gln-(Arg)6, (Arg)2-Gln-(Arg)7, (Arg)3-Gln-(Arg)5, (Arg)3-Gln-(Arg)6, (Arg)4-Gln-(Arg)4, (Arg)4-Gln-(Arg)5, (Arg)5, (Arg)5-Gln-(Arg)3, (Arg)5-Gln-(Arg)4, (Arg)6, (Arg)6-Gln-(Arg)3, (Arg)7, (Arg)7-Gln-(Arg)2, (Arg)8, (Arg)8-Gln-Arg, (Arg)9, (Arg)9-Gln, (D-Arg)5, (D-Arg)6, (D-Arg)7, (D-Arg)8, (D-Arg)9, Gln-Arg-(Lys)2-(Arg)5, Gln-(Arg)8, Gln-(Arg)9, Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc이거나 생략되며;
B2는 β-Ala, β-Ala-Gly, β-Ala-Tyr, β-Ala-Tyr-Gly, (β-Ala)2, (β-Ala)2-Gly, (β-Ala)2-Tyr, (β-Ala)2-Tyr-Gly, Doc, Doc-Gly, Doc-Tyr, Doc-Tyr-Gly, (Doc)2, (Doc)2-Gly, (Doc)2-Tyr, Doc)2-Tyr-Gly이거나, 또는 생략되며;
B3는 Arg-Lys-Gln-Lys-(Arg)5, Arg-Lys-(Arg)3-Gln-(Arg)3, Arg-(Lys)2-Arg-Gln-(Arg)4, Arg-(Lys)2-Gln-(Arg)5, Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Arg-(Lys)2-(Arg)3-Gln-(Arg)2, Arg-(Lys)2-(Arg)4-Gln-Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-Gln-(Lys)2-(Arg)5, Arg-Gln-(Arg)7, Arg-Gln-(Arg)8, (Arg)2-Lys-(Arg)2-Gln-(Arg)3, (Arg)2-Gln-(Arg)6, (Arg)2-Gln-(Arg)7, (Arg)3-Gln-(Arg)5, (Arg)3-Gln-(Arg)6, (Arg)4-Gln-(Arg)4, (Arg)4-Gln-(Arg)5, (Arg)5, (Arg)5-Gln-(Arg)3, (Arg)5-Gln-(Arg)4, (Arg)6, (Arg)6-Gln-(Arg)3, (Arg)7, (Arg)7-Gln-(Arg)2, (Arg)8, (Arg)8-Gln-Arg, (Arg)9, (Arg)9-Gln, (D-Arg)5, (D-Arg)6, (D-Arg)7, (D-Arg)8, (D-Arg)9, Gln-Arg-(Lys)2-(Arg)5, Gln-(Arg)8, Gln-(Arg)9이거나, 또는 생략되며;
A1은 A6c, Cha, hCha, Chg, D-Chg, hChg, Gaba, hLeu, Met, β-hMet, D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe, hPro이거나, 또는 생략되며;
A2는 Cys이며;
A3는 D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, Glu, Gly, D-Ile, D-Leu, D-Met, D-Nle, D-Phe, D-Tle, D-Trp, D-Tyr, D-Val이거나, 또는 생략되며;
A4는 His이며;
A5는 D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-(X1,X2,X3,X4,X5)Phe, D-Trp, 또는 D-(Et)Tyr이며;
A6는 Arg 또는 hArg이며;
A7은 Bal, Bip, 1-Nal, 2-Nal, Trp 또는 D-Trp이며;
A8은 A5c, A6c, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly이거나, 또는 생략되며;
A9은 Cys, D-Cys, hCys, D-hCys, Lys, Pen 또는 D-Pen이며;
A10은 Pro, Thr이거나 생략되며;
A11은 Pro이거나 생략되며;
A12은 Arg, Lys이거나, 또는 생략되며;
A13은 Asp이거나 생략되며;
각각의 R2 및 R3는 독립적으로 H 또는 아실이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 식 (III)의 화합물 그룹에 대한 보다 바람직한 화합물은 하기 식의 화합물 또는 그것의 약학적으로 허용가능한 염이다:
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 60)
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 61)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 63)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 64)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 65)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 66)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 67)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 68)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 70)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 72)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 73)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 74)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 75)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2; (서열번호 76)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2; (서열번호 77)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2; (서열번호 78)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 79)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro) 2 -Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 84)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2; (서열번호 85)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2; (서열번호 86)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2; (서열번호 87)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 89)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 90)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 91)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 93)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 94)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 95)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 96)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 97)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 98)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 99)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 102)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 103)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 104)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 105)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 102)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 103)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 106)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2; (서열번호 107)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2; (서열번호 108)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2; (서열번호 109)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2; (서열번호 110)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2; (서열번호 111)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2; (서열번호 112)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 117)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 117)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 123)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 123)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 129)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 129)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 131)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 131)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 132)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 137)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 139)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 140)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 143)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 144)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 145)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 146)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 147)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 147)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 159)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 160)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 177)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 178)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 184)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 195)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 197)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 198)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 201)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 202)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 210)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 267)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 220)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 229)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 231)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 233)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 234)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265) 또는
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266).
제4 구현예에서, 본 발명은 식 (IV)에 따른 멜라노코르틴 수용체 리간드 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 하기 식의 화합물(식 (IV))과 함께 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다:
Ac-c(Cys-Glu-His-A1-Arg-A2-A3-Cys)-(Pro)2-Lys-Asp-NH2
(IV)
상기 식 (IV)에서,
A1은 X가 할로겐인 X-Phe 또는 2-Nal의 D-이성체이고;
A2는 Bal, 1-Nal, 2-Nal, 또는 Trp이고;
A3은 Aib, Ala, β-Ala 또는 Gly이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는 것으로 확인된 상기 식에 대한 보다 바람직한 화합물은 하기 화합물 또는 그것의 약학적으로 허용가능한 염이다:
Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2 ; (서열번호 268)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 2690)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270) 또는
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270).
본 발명은 추가적으로 식 (V), (VI) 또는 (VII)에 따른 히단토인 모이어티로 변형된 멜라노코르틴 수용체 화합물 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다.
제5 구현예에서, 본 발명은 하기 식(식 (V))에 따른 멜라노코르틴 수용체 리간드 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 PCT/US08/06675, 문헌 전체가 원용에 의해 본 발명에 포함됨):
Figure pat00001
상기 식 (V)에서,
X는 -CH2-S-S-CH2-, -C(CH3)2-S-S-CH2-, -CH2-S-S-C(CH3)2-, -C(CH3)2-S-S-C(CH3)2-, -(CH2)2-S-S-CH2-, -CH2-S-S-(CH2)2-, -(CH2)2-S-S-(CH2)2-, -C(CH3)2-S-S-(CH2)2-, -(CH2)2-S-S-C(CH3)2-, -(CH2)t-C(O)-NR8-(CH2)r- 및 -(CH2)r- NR8-C(O)-(CH2)t -로 이루어진 군으로부터 선택되고;
R1 및 R2는 각각 독립적으로 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
R3는 -OH 또는 -NH2이고;
R4 및 R5는 각각 독립적으로 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
X1은
Figure pat00002
이고;
A1은 His, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi, 3-Thi이거나 생략되고;
A2는 D-Bal, D-1-Nal, D-2-Nal, D-Phe 또는 D-(X1,X2,X3,X4,X5)Phe이고;
A3는 Arg, hArg, Dab, Dap, Lys 또는 Orn이고;
A4는 Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe 또는 Trp이고;
R6 및 R7은 각각 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 아릴(C1-C5)알킬, 치환된 (C1-C10)알킬, 치환된 (C1-C10)헤테로알킬 또는 치환된 아릴(C1-C5)알킬이나, 단 R6 및 R7은 함께 연결되어 고리를 형성할 수 있으며;
R8은 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
r은 각 경우에 독립적으로 1, 2, 3, 4 또는 5이며;
t는 각 경우에 독립적으로 1 또는 2이다.
바람직하게는, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는데 유용한 것으로 확인된 전술한 식에 따른 화합물은, X1이 하기 군으로부터 선택되는 화합물을 포함한다:
Figure pat00003
Figure pat00004
포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는데 유용한 전술한 화합물 클래스에 대한 각각의 구현예는 다음과 같다:
c[히단토인(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
c[히단토인(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
c[히단토인(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
c[히단토인(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2 (서열번호 274)
c[히단토인(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2(서열번호 275)
c[히단토인-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2 (서열번호 277).
제6 구현예에서, 본 발명은 식 (VI)에 따른 멜라노코르틴 수용체 화합물 및 그것의 약학적으로 허용가능한 염, 수화물, 용매화물 또는 프로드럭을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 번호 PCT/US08/06675, 문헌 전체가 원용에 의해 본 발명에 포함됨):
Figure pat00005
상기 식 (VI)에서,
X1은
Figure pat00006
이고;
X2는
Figure pat00007
이고;
A1은 Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen 또는 D-Pen이고;
A2은 L- 또는 D-아미노산이고;
A3는 His, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi 또는 3-Thi이고;
A4는 D-Bal, D-1-Nal, D-2-Nal, D-Phe 또는 D-(X1,X2,X3,X4,X5)Phe이고;
A5은 Arg, hArg, Dab, Dap, Lys 또는 Orn이고;
A6는 Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe 또는 Trp이고;
A7은 Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen 또는 D-Pen이고;
R1은 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
R2 및 R3는 각각 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 아릴(C1-C5)알킬, 치환된 (C1-C10)알킬, 치환된 (C1-C10)헤테로알킬 또는 치환된 아릴(C1-C5)알킬이거나, 또는 R2 및 R3는 서로 융합하여 사이클릭 모이어티를 형성할 수 있으며;
R4는 CO2H 또는 C(O)NH2이고;
R5 및 R6는 각각 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 아릴(C1-C5)알킬, 치환된 (C1-C10)알킬, 치환된 (C1-C10)헤테로알킬 또는 치환된 아릴(C1-C5)알킬이거나, 또는 R5 및 R6는 서로 융합하여 사이클릭 모이어티를 형성할 수 있으며;
R7 및 R8은 각각 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 아릴(C1-C5)알킬, 치환된 (C1-C10)알킬, 치환된 (C1-C10)헤테로알킬 또는 치환된 아릴(C1-C5)알킬이거나, 또는 R7 및 R8는 서로 융합하여 사이클릭 모이어티를 형성할 수 있으며;
R9은 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
n은 각각의 경우에 독립적으로 1, 2, 3, 4, 5, 6 또는 7이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 식 (VI)의 화합물에 대한 보다 바람직한 클래스는, 하기로 정의되는 화합물 또는 그것의 약학적으로 허용가능한 염이다:
A1는 Cys이고;
A2는 D-Ala, Asn, Asp, Gln, Glu 또는 D-Phe이고;
A3는 His이고;
A4는 D-2-Nal 또는 D-Phe이고;
A5는 Arg이고;
A6는 Trp이고;
A7은 Cys 또는 Pen이고;
각각의 R1, R2, R3, 및 R9은 독립적으로 H이고;
R4는 C(O)NH2이고;
각각의 R5 및 R6는 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 치환된 (C1-C10)알킬 또는 치환된 (C1-C10)헤테로알킬이거나, 또는 R5 및 R6는 서로 융합하여 사이클릭 모이어티를 형성할 수 있으며;
각각의 R7 및 R8은 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 치환된 (C1-C10)알킬 또는 치환된 (C1-C10)헤테로알킬이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 식(식 (VI))에 대한 바람직한 화합물은 하기 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 285)
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 285)
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 286)
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 286)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 287)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 287)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 288)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 288)
히단토인(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 289).
제7 구현예에서, 본 발명은 하기와 같이 정의되는 식 (VII)에 따른 구조를 가진 멜라노코르틴 수용체 리간드인 사이클릭 펩타이드 유사체 클래스에 속하는 멜라노코르틴 수용체 리간드 또는 그것의 약학적으로 허용가능한 염을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 번호 PCT/US08/06675, 문헌 전체가 원용에 의해 본 발명에 포함됨):
Figure pat00008
상기 식 (VII)에서,
X는 -CH2-S-S-CH2-, -C(CH3)2-S-S-CH2-, -CH2-S-S-C(CH3)2-, -C(CH3)2-S-S-C(CH3)2-, -(CH2)2-S-S-CH2-, -CH2-S-S-(CH2)2, -(CH2)2-S-S-(CH2)2-, -C(CH3)2-S-S-(CH2)2-, -(CH2)2-S-S-C(CH3)2-, -(CH2)t-C(O)-NR8-(CH2)r- 및 -(CH2)r- NR8-C(O)-(CH2)t -로 이루어진 군으로부터 선택되고;
각각의 R1 및 R5는 독립적으로 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
각각의 R2 및 R3는 독립적으로 H, (C1-C10)알킬, (C1-C10)헤테로알킬, 아릴(C1-C5)알킬, 치환된 (C1-C10)알킬, 치환된 (C1-C10)헤테로알킬 또는 치환된 아릴(C1-C5)알킬이거나, 또는 R2 및 R3는 용합되어 고리를 형성할 수 있으며;
R4는 OH 또는 NH2이고;
각각의 R6 및 R7은 독립적으로 H, (C1-C10)알킬 또는 치환된 (C1-C10)알킬이고;
A1은 L- 또는 D-아미노산이거나 생략되며;
A2는 His, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi 또는 3-Thi이고;
A3는 D-Bal, D-1-Nal, D-2-Nal, D-Phe 또는 D-(X1,X2,X3,X4,X5)Phe이고;
A4는 Arg, hArg, Dab, Dap, Lys 또는 Orn이고;
A5는 Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe 또는 Trp이고;
r은 각각의 경우에 독립적으로 1, 2, 3, 4 또는 5이고;
t는 각각의 경우에 독립적으로 1 또는 2이다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 식 (VII)에 따른 화합물의 바람직한 측면은, 하기로 정의되는 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
A1은 Ala, D-Ala, Asn, Asp, Gln, Glu 또는 Gly임.
포유류 개체에서의 인슐린 내성을 치료하는데 유용한 식 (VII)에 따른 바람직한 화합물은, 하기 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
c[히단토인(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 291)
c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 291).
제8 측면에서, 본 발명은 식 (VIII)에 따른 멜라노코르틴 수용체 화합물 및 그것의 약학적으로 허용가능한 염을 치료학적 유효량으로 투여함으로써, 포유류 대상에서의 인슐린 내성을 체중 감소를 수반하거나 수반하지 않으면서 치료하는 방법을 제공한다(국제 특허 출원 번호 PCT/US08/07411, 문헌 전체가 원용에 의해 본 발명에 포함됨):
(R2R3)- A0-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1
(VIII)
상기 식 (VIII)에서,
A0은 방향족 아미노산이며;
A1은 Acc, HN-(CH2)m-C(O), L- 또는 D-아미노산이며;
A2은 Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen 또는 D-Pen이며;
A3는 Aib, Ala, b-Ala, Gaba, Gly 또는 D-아미노산이며;
A4는 His, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi, 또는 3-Thi이며;
A5는 D-Bal, D-1-Nal, D-2-Nal, D-Phe, L-Phe, D-(X1,X2,X3,X4,X5)Phe, L-Phe, D-Trp 또는 D-(Et)Tyr이며;
A6는 Arg, hArg, Dab, Dap, Lys, Orn, 또는 HN-CH((CH2)n-N(R4R5))-C(O)이며;
A7은 Bal, D-Bal, Bip, D-Bip, 1-Nal, D-1-Nal, 2-Nal, D-2-Nal, 또는 D-Trp이며;
A8은 Acc, Aha, Ahx, Ala, D-Ala, b-Ala, Apn, Gaba, Gly, HN-(CH2)s-C(O)이거나, 또는 생략되며;
A9은 Cys, D-Cys, hCys, D-hCys, Dab, Dap, Lys, Orn, Pen 또는 D-Pen이며;
A10은 Acc, HN-(CH2)t-C(O), L- 또는 D-아미노산이거나, 또는 생략되며;
R1은 OH 또는 NH2이며;
각각의 R2 및 R3는 독립적으로 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C1-C30)아실, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 아릴(C1-C30)아실, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C1-C30)아실, 치환된 (C2-C30)알케닐, 치환된 (C2-C30)알키닐, 치환된 아릴(C1-C30)알킬, 및 치환된 아릴(C1-C30)아실로 이루어진 군으로부터 선택되고;
각각의 R4 및 R5는 독립적으로 H, (C1-C40)알킬, (C1-C40)헤테로알킬, (C1-C40)아실, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 아릴(C1-C40)아실, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C1-C40)아실, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐, 치환된 아릴(C1-C40)알킬, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐, 또는 -C(NH)-NH2이며;
m은 독립적으로 1, 2, 3, 4, 5, 6 또는 7이며;
n은 독립적으로 1, 2, 3, 4 또는 5이며;
s는 독립적으로 1, 2, 3, 4, 5, 6, 또는 7이며;
t는 독립적으로 1, 2, 3, 4, 5, 6, 또는 7이며;
X1, X2, X3, X4, 및 X5는 각각 독립적으로 H, F, Cl, Br, I, (C1 -10)알킬, 치환된 (C1 -10)알킬, (C2 -10)알케닐, 치환된 (C2 -10)알케닐, (C2 -10)알키닐, 치환된 (C2 -10)알키닐, 아릴, 치환된 아릴, OH, NH2, NO2, 또는 CN이나,
단,
(I). R4가 (C1-C40)아실, 아릴(C1-C40)아실, 치환된 (C1-C40)아실, 치환된 아릴(C1-C40)아실, (C1-C40)알킬설포닐, 또는 -C(NH)-NH2이면, R5는 H, (C1-C40)알킬, (C1-C40)헤테로알킬, (C2-C40)알케닐, (C2-C40)알키닐, 아릴(C1-C40)알킬, 치환된 (C1-C40)알킬, 치환된 (C1-C40)헤테로알킬, 치환된 (C2-C40)알케닐, 치환된 (C2-C40)알키닐, 또는 치환된 아릴(C1-C40)알킬이고;
(II). R2가 (C1-C30)아실, 아릴(C1-C30)아실, 치환된 (C1-C30)아실 또는 아릴(C1-C30)아실이면, R3는 H, (C1-C30)알킬, (C1-C30)헤테로알킬, (C2-C30)알케닐, (C2-C30)알키닐, 아릴(C1-C30)알킬, 치환된 (C1-C30)알킬, 치환된 (C1-C30)헤테로알킬, 치환된 (C2-C30)알케닐, 치환된 (C2-C30)알키닐 또는 치환된 아릴(C1-C30)알킬이고;
(III). A2가 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이면, A9은 Cys, D-Cys, hCys, D-hCys, Pen 또는 D-Pen이며;
(IV). A2가 Asp 또는 Glu이면, A9은 Dab, Dap, Orn, 또는 Lys이며;
(V). A8이 Ala 또는 Gly이면, A1은 Nle이 아니다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 식의 화합물에 대한 바람직한 그룹은, 하기로 정의되는 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
A0는 1-Nal, 2-Nal, His, Pff, Phe, Trp, 또는 Tyr이고;
A1은 Arg이고;
A2는 Cys이고;
A3는 D-Ala이고;
A4는 His이고;
A5는 D-Phe이고;
A6은 Arg이고;
A7은 Trp이고;
A8은 생략되고;
A9은 Cys이고;
A10은 생략된다.
체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 상기 식의 화합물에 대한 바람직한 화합물은, 하기 식의 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 293)
Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292).
또다른 바람직한 구현예에서, 체중 감소를 수반하거나 수반하지 않고 포유류 개체에서의 인슐린 내성을 치료하는데 유용한 전술한 바와 같이 정의되는 식 (I), (II), (III), (IV), (V), (VI), (VII) 또는 (VIII)의 화합물 또는 화합물들, 또는 그것의 약학적으로 허용가능한 염은, 약학적으로 허용가능한 담체나 희석제와의 조성물로서 필요한 개체에게 제공된다.
바람직한 구현예에서, 본 발명은 필요한 개체에게서 인슐린 내성을 치료하기 위해 멜라노코르틴 수용체 4 작용제를 유효량으로 말초 투여하는 단계를 포함하는, 필요한 개체에서 인슐린 내성을 치료하는 방법을 제공한다.
일 측면에서, 체중 감소를 수반하면서 또는 수반하지 않으면서 필요한 개체에서 인슐린 내성을 치료하는데 유용한 상기 멜라노코르틴 수용체 4는 하기 군으로부터 선택되는 화합물 또는 그것의 약학적으로 허용가능한 염을 포함한다:
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; 서열번호 1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; 서열번호 1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; 서열번호 2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; 서열번호 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-b-Ala-D-Cys)-Thr-NH2; 서열번호 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; 서열번호 3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; 서열번호 4
Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-b-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
n-부타노일-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; 서열번호 14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; 서열번호 14
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; 서열번호 15
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; 서열번호 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; 서열번호 16
n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 17
n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 17
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; 서열번호 18
Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 61
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; 서열번호 19
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; 서열번호 20
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 27
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; 서열번호 28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; 서열번호 28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; 서열번호 29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 31
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 37
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-b-Ala-Lys)-NH2; 서열번호 38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; 서열번호 39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; 서열번호 39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; 서열번호 41
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; 서열번호 42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; 서열번호 43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; 서열번호 43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; 서열번호 43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; 서열번호 42
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; 서열번호 41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-b-Ala-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; 서열번호 45
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; 서열번호 46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; 서열번호 46
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 47
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; 서열번호 48
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 54
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; 서열번호 57
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2; 서열번호 58
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 60)
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 61)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 63)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 64)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 65)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 66)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 67)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 68)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 70)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 72)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 73)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 74)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 75)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2; (서열번호 76)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2; (서열번호 77)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2; (서열번호 78)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 79)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro) 2 -Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 84)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2; (서열번호 85)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2; (서열번호 86)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2; (서열번호 87)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 89)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 90)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 91)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 95)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 96)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 97)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 98)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 99)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 104)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 105)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 102)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 103)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 137)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 139)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 140)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 143)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 144)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala- (Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149);
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 159)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 160)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(서열번호 169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 177)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 178)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 184)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 195)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 197)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 198)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 201)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 202)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 210)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 267)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 220)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 229)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 231)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 233)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 234)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266)
Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2 ; (서열번호 268)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270)
c[히단토인(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
c[히단토인(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
c[히단토인(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
c[히단토인(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 273)
c[히단토인(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인 (C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
c[히단토인(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 276)
c[히단토인(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 277)
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
히단토인(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
히단토인(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 285)
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 285)
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 286)
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 286)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 287)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 288)
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 288)
히단토인(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 289)
c[히단토인(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2, (서열번호 290)
c[히단토인(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 291)
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 293)
Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292).
바람직한 일 측면에서, 필요한 개체에서 인슐린 내성을 치료하는데 유용한 상기 멜라노코르틴 수용체 4 작용제는 Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 50) 또는 그것의 약학적으로 허용가능한 염이다. 다른 바람직한 측면에서, 필요한 개체에서 인슐린 내성을 치료하는데 유용한 상기 멜라노코르틴 수용체 4 작용제는 히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 또는 그것의 약학적으로 허용가능한 염이다.
본 발명의 다른 측면에서, 인슐린 내성을 치료하는데 유용한 본 바명의 화합물 또는 그것의 약학적인 염을 포함하는 조성물이나 화합물의 투여는 연속적으로, 매시간, 매일 4회, 매일 3회, 매일 2회, 매일 1회, 이틀에 1회, 매주 2회, 매주 1회, 2주에 1회, 매달 1회, 또는 2달에 1회 또는 그 이상으로 이루어진다.
치료가 필요한 개체는 비만, 과체중 또는 정상 체중이거나 저체중일 수 있다. 비만, 과체중, 정상 체중 또는 저체중 개체는 2형 당뇨병을 앓고 있을 수 있다. 인슐린 내성 치료에 유용한 본 발명의 화합물 또는 그것의 약학적인 염을 포함하는 조성물이나 화합물의 바람직한 투여 방법은 말초 투여이다. 말초 투여 방법의 예는 경구, 피하, 복막내, 근육내, 정맥내, 직장, 경피 또는 경비 투여 형태이다.
당업자들에게 잘 알려져 있는 바와 같이, 멜라노코르틴 수용체(MC-R) 작용제 또는 길항제 활성을 가질 펩타이드의 공지된 용도 및 잠재적인 용도는 다양하고 다채로워, 작용제 작용을 도출하기 위한 목적으로 본 발명의 화합물을 투여하면 멜라노코르틴 그 자체와 동일한 효과 및 용도를 가질 수 있다.
도 1. 선택 화합물을 100 nmole/Kg으로 투여한 지 6시간 후의 금식시킨 랫에서의 음식 섭취량.
도 2. 랫에서의 (A) 체중, (B) 음식물 누적 섭취량, (C) 인슐린 농도 및 (D) 글루코스 농도에 대한 화합물 A 75, 300 또는 600 nmole/kg/day의 피하 투여 효과.
도 3. 랫에서의 (A) 체중, (B) 음식물 누적 섭취량, (C) 인슐린 농도 및 (D) 글루코스 농도에 대한 화합물 B 75, 300 또는 600 nmole/kg/day의 피하 투여 효과.
도 4. 마우스에서의 혈당 수치에 대한 화합물 A 200, 600 또는 1800 nmole/kg/day의 피하 투여 효과.
도 5. 비만 마우스에서의 혈당 수치에 대한 화합물 A 6.4 umole/kg의 복막내 투여 효과.
최근 연구들에서, 매우 많은 전세계 인구가 과체중이며 매우 심각하고 비용이 많이 드는 매우 다양한 건강상의 문제를 앓고 있는 것으로 보고되었으며(Kouris-Blazos et al ., Asia Pac. J. Clin. Nutr., 2007, 16:329-338), 세계적으로 약 10억 명이 과체중이고 이들 중 약 3억명 가량이 비만으로 추정되었다. 5세 미만의 어린이 중에서 약 2,200만 명이 고도 과체중이며, 유럽에서만도 과체중인 어린이의 수는 해마다 130만 명씩 증가하는 것으로 추정되고 있다(Kosti et al., 2006, Cent. Eur. J. Public Health, 14:151-159). 메트로폴리탄 생명보험사에서 제공한 통계 보고(1959, 40:1)에 따르면, 비만은 체중이 정상 체중 보다 약 20-25% 높은 상태이다. 다른 예로, 개체의 체질량 지수가 정상 보다 25%가 이상이거나 또는 위험 인자를 가진 정상 보다 30% 이상이라면, 그 개체는 비만으로 본다(Bray et al ., Diabetes/Metabolism Review, 1988, 4:653-679; Flynn et al ., Proc. Nutritional Society, 1991, 50:413). 비만의 주된 요인 중 한가지는 고열량 식이 섭취이다(Riccardi et al ., Clin. Nutr., 2004, 23:447-456).
당뇨병은 많은 과체중 및 비만인 사람이 앓고 있는 만성적인 허약성 질환이다. 미국에서만도 2080만 명의 사람들이 당뇨병을 가지고 있으며 600만 명 이상의 사례들은 진단 미확정 상태인 것으로 추산되고 있다(Cornell, Manag. Care Pharm., 2007, 13:S11-5). 2형 당뇨병(또한, II형 당뇨병이라고도 함)은 인슐린 내성, 인슐린 분비 결합 및 고혈당이 특징적인 만성 질환이다. 전세계적으로, II형 당뇨병에 걸린 사람은 약 17,100만명에 이르는 것으로 생각되고 있으며, 이는 질병 및 사망을 초래하는 수많은 미세혈관 및 거대혈관 합병증을 일으킨다(Mudaliar, Indian J. Med. Res., 2007, 125:275-296). 또한, 무달리아르는, 입수가능한 항-고혈당제의 이용가능성에도 불구하고, 다수의 사람들에서는 혈당을 조절하기 어렵다는 것을 언급하였다.
인슐린 민감성 감소라고도 하는 인슐린 내성은, 개체의 혈액으로부터 글루코스를 소비하는데 필요한 인슐린의 양이 인슐린에 민감하지 않은 개체인 정상인의 혈액으로부터 동량의 글루코스를 소비하는데 필요한 인슐린 양 보다 많은 상태이다. 인슐린 내성은 비만과 II형 당뇨병을 연결짓는 주된 고리로 간주되고 있다(Obici et al., J. Clin. Inv., 2001, 108:1079-1085 및 상기 문헌의 참고문헌). 고지방식이를 하는 랫에게서 체중은 증가하고(식이-유발성 비만 또는 DIO) 인슐린 민감성은 감소하는 것으로 확인되었다. 이러한 DIO 랫는, 비만으로 인한 인슐린 내성 메카니즘을 연구하기 위한 동물 모델이 된다(예로, Banno et al., FEBS letters, 2007, 581:1131-1136 참조). 지방 조직의 크기와 무게가 DIO 랫에서 증가하는데, 이렇게 동반되는 지방 조직의 비대화는 인슐린 민감성을 조절하는 것으로 알려져 있는 렙틴 및 아디포넥틴과 같은 아디포사이토카인의 분비를 변화시키는 것으로 생각되며, 그 중에서도 지방 조직의 형태적 변화 뿐만 아니라 아디포사이토카인의 혈장 농도 변화가 DIO 랫에서의 인슐린 내성 발병의 요인인 것으로 생각된다(Banno, et al., FEBS letters, 2007, 581:1131-1136 및 상기 문헌의 참조문헌).
멜라노코르틴은 에너지 대사와 항상성에서 큰 역할을 담당하는 것으로 예상되고 있다. POMC 전구체로부터 절단되는 멜라노코르틴은 뇌에 위치하는 멜라노코르틴 수용체 패밀리 일원에 결합함으로써 이의 작용을 발휘한다. 뇌에서의 멜라노코르틴의 주된 작용은 음식물 섭취를 감소시키는 것이지만, 대뇌 뇌실에 직접 주입된 멜라노코르틴 작용제나 길항제가 말초에서 인슐린 작용에 영향을 미치며, 금식하거나 또는 음식물 섭취를 일정하게 유지시킨다(Schwartz et al., Nature, 2000, 404:661-671; Seeley et al., Ann. Rev. Nutr., 2004, 24:133-149; Cone et al., Recent Prog. Horm. Res., 1996, 51:287-317; Heijbor et al., Diabetologia, 2005, 48:1621-1626; Obici et al., J. Clin. Inv., 2001, 108:1079-1085). 종합하면, 이들 데이타는, 멜라노코르틴의 중추 투여가 인슐린 민감성에 영향을 미치며, 에너지 밸런스와 독립적으로 작용할 수 있다는 것을 시사한다. Banno 등(FEBS letters, 2007, 581:1131-1136)은, DIO 랫에 멜라노코르틴 작용제의 뇌내 주입이 말초에서의 인슐린 민감성을 완화시키고, 백색 지방 조직에서의 지방 세포의 크기를 줄이고 수를 증가시키고, 간에서의 트리글리세라이드 양을 낮춘다는 것을 입증하였다.
치료가 필요한 과체중 및/또는 인슐린 내성 개체의 수가 많을 것을 고려하면, 뇌내 주사는 환자에게 약제를 전달하기 위한 수단이 되기 어렵다. 따라서, 당해 분야에서는 인슐린 민감성, 백색 지방 조직의 세포적 특징들, 트리글리세라이드 농도 등의 인슐린 작용과 에너지 대사의 파라미터에 작용하기 위해, 말초 투여용으로 적합한 멜라노코르틴 작용제와 길항제의 동정이 요구되어 있다.
명명 및 약어
본원에서, "비만 개체"나 포유류는 개체의 정상 체중에 약 20% 이상의 체중을 갖는 개체로 특정된다. 정상 체중은 인슐린 대사가 정상적일 때 등과 같은 시기 전에 개체의 체중과 비교함으로써, 또는 나이 및/또는 상태가 비슷한 다른 개체의 평균과 비교함으로써, 결정할 수 있다.
본원에서, "과체중 개체"나 포유류는 상기 개체의 정상 체중에 약 5% 이상 내지 약 20% 이상의 체중을 가진 것으로 특정화된다. 정상 체중은 인슐린 대사가 정상적일 때 등과 같은 시기 전에 개체의 체중과 비교함으로써, 또는 나이 및/또는 상태가 비슷한 다른 개체의 평균과 비교함으로써, 결정할 수 있다.
본원에서, "정상 개체"나 포유류는 상기 개체의 정상 체중의 최대 약 5% 이상 내지 약 5% 이하의 체중을 갖는 것으로 특정화된다. 정상 체중은 인슐린 대사가 정상적일 때 등과 같은 시기 전에 개체의 체중과 비교함으로써, 또는 나이 및/또는 상태가 비슷한 다른 개체의 평균과 비교함으로써, 결정할 수 있다.
본원에서, "저체중 개체" 또는 포유류는 개체의 정상 체중의 약 5% 내지 30% 미만이거나, 또는 심지어 50% 미만의 체중을 갖는 것으로 특정화된다. 정상 체중은 인슐린 대사가 정상적일 때 등과 같은 시기 전에 개체의 체중과 비교함으로써, 또는 나이 및/또는 상태가 비슷한 다른 개체의 평균과 비교함으로써, 결정할 수 있다.
본원에서, 용어 "치료하다", "치료하는" 및 "치료"는 완화적, 치유적 및 예방적 치료를 포함한다.
본원에서, "측정가능한"은 생물학적 효과가 재현가능하며 동시에 분석의 베이스라인 가변성과는 현저하게 상이함을 의미한다.
본원에서, 말초 투여는, 두개골내 투여를 제외한, 본 발명의 화합물을 포함하는 조성물 또는 화합물의 모든 투여 형태를 포함한다. 말초 투여의 예로는, 경구, 비경구(예, 근육내, 복막내, 정맥내 또는 피하 주입, 이식 등), 코, 질, 직장, 설하 또는 경피 패치 적용 등이 국소 투여 경로를 들 수 있지만, 이들로 한정되는 것은 아니다.
본원에서, "개체"란, 예컨대 비제한적으로, 인간, 랫, 마우스, 또는 사육 동물 등의 포유류 또는 포유류 이외의 동물을 일컫는다. 개체가 반드시 질병 또는 장애가 있다는 것은 아니다. "개체"란 용어는, 예컨대, 실험의 일부로서 멜라노코르틴 유사체를 투여받고 있는 포유류 또는 포유류 이외의 동물, 질병 또는 장애의 완화를 돕기 위하여 치료받고 있는 포유류 또는 포유류 이외의 동물, 및 질병 또는 장애의 발병을 지연시키거나 예방하기 위하여 예방적으로 치료받는 포유류 또는 포유류 이외의 동물을 포함한다. 개체 포유류는 모든 연령대의 인간, 예컨대 유사, 어린이, 성인, 노인을 포함할 수 있다.
본 발명의 화합물 또는 조성물의 "치료학적인 허용량"은 투여 제형이나 경로와는 무관하게, 개체에게서 원하는 생물학적 반응을 도출시키는 양이다. 치료학적인 양의 생물학적 효과는 유기체에서 여러가지 수준으로 형성되며 이를 측정할 수 있다. 예컨대, 치료학적인 양의 생물학적 효과는 세포 수준에서 발생하며, 멜라노코르틴 및/또는 멜라노코르틴 유사체가 결합하는 수용체에서의 반응을 측정함으로써 세포 수준에서 이를 측정할 수 있거나, 또는 치료학적인 양의 생물학적 효과는 전신 수준에서 발행하며, 인슐린 수준의 증가/감소에 작용하는 것과 같인 전신 수준에서 측정할 수 있다. 치료학적인 양의 생물학적 효과는 개체에서 질병이나 병태의 증상(들) 또는 진행 완화와 같이 유기체 수준에서 나타나며 이를 측정할 수 있다. 본 발명의 화합물 또는 조성물의 치료학적인 허용량은, 투여 제형이나 경로와는 무관하게, 개체에서 한가지 이상의 생물학적인 반응을 발생시킬 수 있다. 본 발명의 화합물 또는 조성물을 시험관내 시스템으로 테스트하는 경우, 화합물 또는 조성물의 치료학적인 허용량은 선택한 시험관내 시스템에서 측정가능한 반응을 보이는 양으로서 간주할 수 있다.
펩타이드를 정의하는데 사용되는 명명은 당업계에 전형적으로 사용되는 방법으로, N-말단의 아미노기는 좌측이고 C-말단의 카르복시기가 우측이다. 아미노산이 D 및 L 이성체 형태를 가지는 경우, 아미노산을 명확하게 나타내지 않은 경우, 아미노산은 L 형태이다.
체중의 감소 또는 감소없이, 인슐린 내성을 치료하기 위해 사용가능한 본 발명의 화합물은, 하나 이상의 키랄 센터를 가질 수 있으며, 그리하여 다수의 입체이성체 형태를 가질 수 있다. 모든 입체 이성체 및 이의 혼합물은 본 발명의 범위에 포함된다. 라세믹 화합물은 분취용 HPLC 및 키랄 정지상을 가진 컬럼을 이용하거 분리하거나 또는 분해하여, 당해 분야의 당업자에게 공지된 방법을 이용하여 각각의 에난티오머를 수득할 수 있다. 또한, 키랄 중가체 화합물을 분해시킬 수 있으며, 이를 본 발명이 키랄 화합물 제조에 사용할 수 있다.
체중의 감소 또는 감소없이, 인슐린 내성을 치료하기 위해 사용가능한 본 발명의 화합물은, 하나 이상의 호변이성체로 존재할 수 있다. 모든 호변이성체 및 이의 혼합물은 본 발명의 범위에 포함된다. 예컨대, 2-하이드록시피리디닐에 대한 청구항은 이의 호변이성체 형태인 α-피리도닐을 포괄한다.
별도로 언급되어 있지 않은 한, 본원에 사용된 모든 기술적 및 과학적 용어는 본 발명이 속하는 기술 분야의 당업자가 통상적으로 이해하는 바와 동일한 의미를 갖는다. 또한, 본원에 언급된 모든 공개문헌, 특허 출원, 특허 및 그외 인용문헌들은 그 전체가 원용에 의해 본 명세서에 포함된다.
기호 의미
Abu α-아미노부티르산
Ac 아실기
Acc 1-아미노-1-사이클로(C3-C9)알킬 카르복시산
A3c 1-아미노-1-사이클로프로판카르복시산
A4c 1-아미노-1-사이클로부탄카르복시산
A5c 1-아미노-1-사이클로펜탄카르복시산
A6c 1-아미노-1-사이클로헥산카르복시산
Aha 7-아미노펩탄산
Ahx 6-아미노헥산산
Aib α-아미노이소부티르산
Aic 2-아미노인단-2-카르복시산
Ala 또는 A 알라닌
β-Ala β-알라닌
Apc 구조식
Figure pat00009
으로 표시됨
Apn 5-아미노펜탄산 (HN-(CH2)4-C(O)
Arg 또는 R 아르기닌
hArg 호모아르기닌
Asn 또는 N 아스파라긴
Asp 또는 D 아스파르트산
Bal 3-벤조티에닐알라닌
Bip 하기 구조로 표시되는 4,4'-바이페닐알라닌
Figure pat00010
Bpa 4-벤조일페닐알라닌
4-Br-Phe 4-브로모-페닐알라닌
Cha β-사이클로헥실알라닌
hCha 호모-사이클로헥실알라닌
Chg 사이클로헥실글리신
Cys 또는 C 시스테인
hCys 호모시스테인
Dab 2,4-디아미노부티르산
Dap 2,3-디아미노프로피온산
Dip β,β-디페닐알라닌
Doc 하기 구조로 표시되는 8-아미노-3,6-디옥사옥타노산
Figure pat00011
2-Fua β-(2-푸릴)-알라닌
Gaba 4-아미노부티르산
Gln 또는 Q 글루타민
Glu 또는 E 글루탐산
Gly 또는 G 글리신
His 또는 H 히스티딘
3-Hyp 트랜스-3-하이드록시-L-프롤린,
즉, (2S, 3S)-3-하이드록시피롤리딘-2-카르복시산
4-Hyp 4-하이드록시프롤린,
즉, (2S, 4R)-4-하이드록시피롤리딘-2-카르복시산
Ile 또는 I 이소루신
Leu 또는 L 루신
hLeu 호모루신
Lys 또는 K 라이신
Met 또는 M 메티오닌
β-hMet β-호모메티오닌
1-Nal β-(1-나프틸)알라닌
2-Nal β-(2-나프틸)알라닌
Nip 니펙코트산
Nle 노르루신
Oic 옥타하이드로인돌-2-카르복시산
Orn 오르니틴
2-Pal β-(2-피리디일)알라닌)
3-Pal β-(3-피리디일)알라닌)
4-Pal β-(4-피리디일)알라닌)
Pen 페니실아민
Pff (S)-펜타플루오로페닐알라닌
Phe 또는 F 페닐알라닌
hPhe 호모페닐알라닌
Pro 또는 P 프롤린
hPro 호모프롤린
Ser 또는 S 세린
Tle tert-루신
Taz β-(4-티아졸릴)알라닌
2-Thi β-(2-티아졸릴)알라닌
3-Thi β-(3-티아졸릴)알라닌
Thr 또는 T 트레오닌
Trp 또는 W 트립토판
Tyr 또는 Y 타이로신
D-(Et)Tyr 하기 구조로 표시되는 화합물
Figure pat00012
Val 또는 V 발린
본원에 사용된 그외 특정 약어는 다음과 같이 정의된다:
Boc: tert-부틸옥시카르보닐
Bzl: 벤질
DCM: 디클로로메탄
DIC: N,N-디이소프로필카르보디이미드
DIEA: 디이소프로필에틸아민
Dmab: 4-{N-(1-(4,4-디메틸-2,6-디옥소사이클로헥실리덴)-3-메틸부틸)-아미노}벤질
DMAP: 4-(디메틸아미노)피리딘
DMF: 디메틸포름아미드
DNP: 2,4-디니트로페닐
Fm: 플루오레닐메틸
Fmoc: 플루오레닐메틸옥시카르보닐
For: 포르밀
HBTU: 2-(1H-벤조트리아졸-1-일)-1,1,3,3-테트라메틸우로늄 헥사플루오로포스페이트
cHex: 사이클로헥실
HOAT: O-(7-아자벤조트리아졸-1-일)-1,1,3,3-테트라메틸우로늄 헥사플루오로포스페이트
HOBt: 1-하이드록시-벤조트리아졸
MBHA: 4-메틸벤즈하이드릴아민
Mmt: 4-메톡시트리틸
NMP: N-메틸피롤리돈
O-tBu: 옥시-tert-부틸
Pbf: 2,2,4,6,7-펜타메틸디하이드로벤조퓨란-5-설포닐
PyBroP: 브로모-트리스-피롤리디노-포스포늄 헥사플루오로포스페이트
tBu: tert-부틸
TIS: 트리이소프로필실란
TOS: 토실
Trt: 트리틸
TFA: 트리플루오로 아세트산
TFFH: 테트라메틸플루오로포름아미디늄 헥사플루오로포스페이트
Z: 벤질옥시카르보닐.
언급되어 있지 않은 한, 본원에서, N-말단 아미노산을 제외하고는, 아미노산의 모든 약어(예, Ala)는 구조 -NH-C(R)(R')-CO-를 유지하며, 여기에서 R 및 R'은 각각 독립적으로 수소 또는 아미노산의 측쇄(예, Ala의 경우, R = CH3 및 R' = H)이거나, R 및 R'은 연결되어 고리 시스템을 형성할 수 있다.
N-말단 아미노산은 하기 구조이다:
Figure pat00013
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2에서, "NH2"는 펩타이드의 C-말단이 아미드화되었음을 나타낸다. Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) (서열번호 36), 또는 대안적으로 AAc-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH (서열번호 36)는, C-말단이 유리산임을 나타낸다.
"-c(Cys-Cys)-" 또는 "-사이클로(Cys-Cys)-"는 하기 구조이다:
Figure pat00014
"-c(Cys-Pen)-" 또는 "-사이클로(Cys-Pen)-"은 하기 구조이다:
Figure pat00015
"-c(Asp-Lys)-" 또는 "-사이클로(Asp-Lys)-"은 하기 구조를 나타낸다:
Figure pat00016
출원인은 구체적인 구현예에서 언급한 하기 약칭 및/또는 종을 고안하였다:
"히단토인 C(O)-(Aa-Ab)"는 구조:
Figure pat00017
이며,
이때, 아미노산 "Aa"는 구조:
Figure pat00018
이고, 아미노산 "Ab"는 구조:
Figure pat00019
이다.
예컨대, "c[히단토인(C(O)-(Cys-Ab))-A1-A2-A3-A4-Cys]-"로 표시되는 화합물은 하기 구조를 가지며:
Figure pat00020
"c[히단토인(C(O)-(Ab-Cys))-A1-A2-A3-A4-Cys]-"로 표시되는 화합물은 하기 구조를 가진다:
Figure pat00021
추가적인 예로, "c[히단토인(C(O)-(Asp-Ab))-A1-A2-A3-A4-Lys]-"은 화합물:
Figure pat00022
이나, "c[히단토인(C(O)-(Dap-Ab))-A1-A2-A3-A4-Asp]-"은 식:
Figure pat00023
을 가진다.
"아실"은 R"이 H, 알킬, 치환된 알킬, 헤테로알킬, 치환된 헤테로알킬, 알케닐, 치환된 알케닐, 아릴, 알킬아릴 또는 치환된 알킬아릴인, R"-C(O)-이며, 특정 구현예의 일반식에서 "Ac"로 표시된다.
"알킬"은 복수의 탄소 원자가 존재하다면 단일 결합으로 연결되어 있는, 하나 이상의 탄소 원자를 포함하고 있는 탄화수소기이다. 알킬 탄화수소기는 직쇄일 수 있거나, 또는 하나 이상의 분지 또는 사이클기를 포함할 수도 있다.
"하이드록시알킬"은 탄화수소기에서 하나 이상의 수소 원자가 하이드록시메틸, 하이드록시에틸, 하이드록시프로필, 하이드록시부틸, 하이드록시펜틸, 하이드록시헥실 등과 같은 하나 이상의 하이드록시 라디칼로 치환된 알킬기이다.
"치환된 알킬"은 탄화수소기에서 하나 이상의 수소 원자가, 할로겐(즉, F, l, Br 및 I), -OH, -CN, -SH, NH2, -NHCH3, -NO2, 및 각 경우에 독립적으로 할로겐, -CF3, -OCH3, -OCF3 및 -(CH2)0-20-COOH로 이루어진 군으로부터 하나 이상의 치환기로 선택적으로 치환될 수 있는 -C1 -20 알킬로 이루어진 군으로부터 선택된 하나 이상의 치환기로 치환된, 알킬이다. 여러가지 구현예에서, 1, 2, 3 또는 4개의 치환기가 존재한다. -(CH2)0-20-COOH이 존재하면, 알킬 산이 생성된다. -(CH2)0-20-COOH를 포함하는 알킬 산 또는 -(CH2)0-20-COOH로 이루어진 알킬 산의 예로는, 2-노르보난 아세트산, tert-부티르산 및 3-사이클로펜틸 프로피온산 등이 있으나, 이로 한정되지 않는다.
용어 "할로"는 F, Cl, Br 및 I를 나타낸다.
"헤테로알킬"은 탄화수소기에서 하나 이상의 탄소 원자가 아미노, 아미도, -O-, -S- 또는 카르보닐 중 하나 이상으로 치환된 알킬이다. 여러가지 예에서, 1 또는 2개의 헤테로원자가 존재한다.
"치환된 헤테로알킬"은 탄화수소기에서 하나 이상의 수소 원자가 할로겐(즉, F, l, Br 및 I), -OH, -CN, -SH, NH2, -NHCH3, -NO2, 및 각 경우에 독립적으로 할로겐, -CF3, -OCH3, -OCF3 및 -(CH2)0-20-COOH로 이루어진 군으로부터 하나 이상의 치환기로 선택적으로 치환될 수 있는 -C1 -20 알킬로 이루어진 군으로부터 선택된 하나 이상의 치환기로 치환된, 헤테로알킬이다. 여러가지 예에서, 1, 2, 3 또는 4개의 치환기가 존재한다.
"알케닐"은 하나 이상의 탄소-탄소 이중 결합이 존재하는 2개 이상의 탄소로 구성된 탄화수소기이다. 알케닐 탄화수소기는 직쇄이거나, 또는 하나 이상의 분지 또는 사이클기를 포함할 수도 있다.
"치환된 알케닐"은 하나 이상의 수소가 할로겐(즉, F, l, Br 및 I), -OH, -CN, -SH, NH2, -NHCH3, -NO2, 및 각 경우에 독립적으로 할로겐, -CF3, -OCH3, -OCF3 및 -(CH2)0-20-COOH로 이루어진 군으로부터 하나 이상의 치환기로 선택적으로 치환될 수 있는 -C1 -20 알킬로 이루어진 군으로부터 선택된 하나 이상의 치환기로 치환된, 알케닐이다. 여러가지 예에서, 1, 2, 3 또는 4개의 치환기가 존재한다.
"아릴"은 최대 3개의 공액된(conjugated) 또는 융합된(fused) 고리 시스템을 포함하며, 공액된 파이-전자 시스템(pi-electron system)을 가지고 있는 하나 이상의 고리를 가진 선택적으로 치환된 방향족 기를 일컫는다. 아릴은 카르보사이클 아릴, 헤테로사이클 아릴 및 바이아릴기를 포함한다. 바람직하기로는, 아릴은 5 또는 6원환이다. 헤테로사이클 아릴에 바람직한 원자는, 하나 이상의 황, 산소 및/또는 질소이다. 아릴의 예로는, 페닐, 1-나프틸, 2-나프틸, 인돌, 퀴놀린, 2-이미다졸 및 9-안트라센 등이 있으나, 이로 한정되지 않는다. 아릴 치환기는 -C1 -20 알킬, -C1 -20 알콕시, 할로겐(즉, F, Cl, Br 및 I), -OH, -CN, -SH, -NH2, -NO2, 및 할로겐, -CF3, -OCF3 또는 -(CH2)0-20-COOH로 치환된 -C1 -20 알킬로 이루어진 군으로부터 선택된다. 여러가지 예에서, 아릴은 0, 1, 2, 3 또는 4개의 치환기를 포함한다.
"알킬아릴"은 "아릴"이 연결된 "알킬"이다.
용어 "(C1-C12)탄화수소 모이어티"는 알킬, 알케닐 및 알키닐을 포함하며, 알케닐 및 알키닐의 경우에는 C2-C12이다.
의심할 여지를 없애기 위해, 별도로 언급된 경우를 제외하고는, 용어 치환된은 하나 이상의 정의된 기로 치환된 것을 의미한다. 기를 대안적인 다수이 기들 중에서 선택할 수 있는 경우, 선택되는 기는 동일하거나 상이할 수 있다. 명확하게 하기 위해, 용어 독립적으로는 2 이상의 치환기가 가능한 다수의 치환기들 중에서 선택되는 경우, 이러한 치환기들이 동일하거나 상이할 수 있음을 의미한다.
염기성 센터를 포함하는 본 발명의 화합물의 약학적으로 허용가능한 염은, 예컨대 하이드로클로르산, 하이드로브롬산, 하이드로요오드산, 설푸르산 및 포스포르산 등의 무기산, 카르복시산, 또는 유기-설폰산과 형성된 무독성의 산 부가염이 있다. 그 예로는, HCl, HBr, HI, 설페이트 또는 바이설페이트, 니트레이트, 포스페이트 또는 하이드로겐 포스페이트, 아세테이트, 벤조에이트, 숙시네이트, 사카레이트, 퓨마레이트, 말레이트, 락테이트, 시트레이트, 타르트레이트, 글루코네이트, 캄실레이트, 메탄설포네이트, 에탄설포네이트, 벤젠설포네이트, p-톨루엔설포네이트 및 파모에이트 염을 포함한다. 또한, 본 발명의 화합물은, 염기와의. 약학적으로 허용가능한 금속 염, 특히 무독성 알카리 및 알칼라인 토 금속염을 제공할 수 있다. 그 예로는, 소듐, 포타슘, 알루미늄, 칼슘, 마그네슘, 아연 및 디에탄올아민 염을 포함할 수 있다(Berge, S. M. et al ., J. Pharm . Sci., 66:1-19 (1977); Gould, P.L., Int'l J. Pharmaceutics, 33:201-17 (1986); Bighley, L.D. et al., Encyclo. Pharma . Tech., Marcel Dekker Inc, New York, 13:453-97 (1996).
본 발명의 화합물의 약학적으로 허용가능한 용매화물은 그것의 수화물을 포함한다. 또한, 이는 본 발명의 범위에 포함되며, 본 발명의 다양한 염은 그것의 다형체이다. 이하, 본 발명의 모든 측면에서 명시된, 화합물, 그것의 약학적으로 허용가능한 염, 그것의 용매화물 또는 다형체(화학 공정에서의 중간체 화합물 제외)는 "본 발명의 화합물"로 언급된다.
시험관내 연구
본 발명의 화합물은 하기 공정에 따라 하나 이상의 멜라노코르틴 수용체의 리간드로서의 활성을 가질 수 있으며, 이를 테스트하였다. 본원에 기술된 공정과 유사한 공정을 사용하여 본 발명의 화합물의 멜라노코르틴 수용체 분자에 결합하는 활성을 분석할 수 있음을, 당업자는 알 것이다.
방사능 표지된 리간드(Radioligand)의 결합 분석
시험관내 수용체 결합 분석에 사용되는 세포막은, hMC-R 수용체 서브타입 1, 3, 4 또는 5를 안정적으로 발현하는 CHO-K1 형질전환주로부터 수득하였다. 원하는 hMC-R 수용체를 발현하는 CHO-K1 세포를, pH 7.4의 빙냉한 50 mM Tris-HCl 중에서 초음파처리한 다음(Branson® 7로 설정, 약 30초), 약 4 ℃에서 39,000 g에서 10분간 원심분리하였다. 펠렛을 동일한 완충액에 재현탁하고, 약 4 ℃에서 50,000 g에서 10분간 원심분리하였다. 세포막 성분이 함유된 세정한 펠렛을 약 -80 ℃에 보관하였다.
[125I](Tyr2)-(Nle4-D-Phe7)α-MSH ([125I]-NDP-α-MSH, Amersham Biosciences®) 결합에 대한 경쟁적 저해는, 폴리프로필렌 96 웰 플레이트에서 수행하였다. 전술한 바와 같이 준비한 세포막(1-10 ㎍ 단백질/웰)을 테스트 화합물의 농도를 증가시키면서 0.2% 소 혈청 알부민(BSA), 5 mM MgCl2, 1 mM CaCl2 및 0.1 mg/mL 박시트라신이 함유된 pH 7.4의 50 mM Tris-HCl 중에서 0.1-0.3 nM [125I]-NDP-α-MSH와 함께 90-12분간 약 37 ℃에서 인큐베이션하였다. Packard Filtermate® 수거기를 이용하여, 0.1 % (w/v) 폴리에틸렌이민(PEI)으로 미리 침지시킨 GF/C 유리 섬유 필터 플레이트(Unifilter®; Packard)를 통한 여과에 의해, 유리 [125I]-NDP-α-MSH로부터, 결합된 [125I]-NDP-α-MSH 리간드를 분리시켰다. 필터를 약 0-4 ℃에서, pH 7.4의 50 mM Tris-HCl을 이용하여 3번 세정한 다음, Packard Topcount® 신틸레이션 카운터를 이용하여 방사능을 분석하였다. 결합성 데이타는 컴퓨터를 이용한 비선형 회귀 분석으로 분석하였다(XL fit; IDBS). 선택한 바람직한 구현예를 상기 분석으로 테스트하였고, 결합 상수(Ki, nM)를 표 5 - 13에 나타내었다.
표 5 - 7: 선택 화합물의 방사능리간드 결합 분석 데이타
화합물 Ki
hMC1-R		 Ki
hMC3-R		 Ki
hMC4-R		 Ki
hMC5-R		 Ki
hMC1-R/MC4-R		 서열번호
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 3.87 10.1 2.09 430 1.9 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 4.01 12.1 1.76 352 2.3 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 8.29 13.3 2.78 816 3.0 51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 3.93 172 11.0 538 0.36 52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 1.81 20.5 4.57 502 0.4 52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 9.67 22.0 4.2 1900 2.3 51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 0.79 45.5 1.21 493 0.6 53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 0.68 20.7 1.01 783 0.7 53
화합물 Ki
hMC1-R		 Ki
hMC3-R		 Ki
hMC4-R		 Ki
hMC5-R		 Ki
hMC1-R/MC4-R		 서열번호
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2 114 63.9 3.07 1657 37.1 16
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 11 26 7.6 1800 1.4 7
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-b-Ala-D-Cys)-Thr-NH2 0.05 9.3 1.1 2.9 0.0 24
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 0.07 4.1 0.85 8.8 0.1 27
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 0.12 10 0.43 0.42 0.3 32
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.05 1.3 0.47 0.2 0.1 34
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-b-Ala-Lys)-NH2 0.0996 9318 0.617 10.9 0.16 1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2 .0132 16.1 1.23 0.359 0.11 2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-b-Ala-D-Cys)-Thr-NH2 0.207 43.2 2.58 344 0.08 3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2 0.420 106 4.75 1260 0.09 3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 0.0951 9.33 0.894 13.4 0.11 2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2 0.999 300 11.1 431 0.09 4
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.106 11.8 1.49 110 0.07 6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.0506 9.89 1.04 16.3 0.05 6
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.884 223 22.5 609 0.04 11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.721 93.5 56.0 747 0.01 11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.227 14.5 2.99 164 0.08 11
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 0.277 25.2 3.37 203 0.08 11
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-b-Ala-Cys)-NH2 0.323 14.1 1.96 24.0 0.16 15
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 34.1 118 17.0 5560 2.01 21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 29.1 22.8 3.84 2550 7.58 22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-b-Ala-D-Cys)-Thr-NH2 0.442 123 10.3 521 0.04 23
D-Phe-c(Cys-His-D-Phe-Arg-Bip-b-Ala-D-Cys)-Thr-NH2 5.80 3370 583 1130 0.01 25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-b-Ala-D-Cys)-Thr-NH2 0.0567 31.4 14.7 9.27 0 24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-b-Ala-D-Cys)-Thr-NH2 1.68 1260 172 1220 0.01 26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-b-Ala-D-Cys)-Thr-NH2 0.128 85.6 36.9 38.0 0 26
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2 0.352 149 3.01 339 0.12 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2 3.93 876 48.0 4940 0.08 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-b-Ala-Cys)-NH2 0.995 287 4.80 766 0.21 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.848 184 3.76 956 0.23 54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 1.10 228 7.58 859 0.15 54
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2 0.659 98.9 2.55 4.19 0.26 28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2 4.12 445 50.6 4300 0.08 28
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 111 1710 47.7 694 2.33 55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 262 2500 96.4 1460 2.72 55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 199 5990 96.7 > 10000 2.06 56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 132 4560 40.7 8810 3.24 56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 9.12 1130 22.1 2860 0.41 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-b-Ala-Cys)-NH2 1.00 227 5.55 496 0.18 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.536 169 3.12 358 0.17 57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH 32.1 330 17.4 165 1.84 29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2 10.6 41.1 7.69 54.9 1.38 30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2 13.0 104 10.1 40 1.29 30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2 4.28 38.5 9.0 12.5 0.48 30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2 1.60 6.82 4.13 5.57 0.39 30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2 12.0 85.8 11.2 40 1.07 30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2 0.353 2.08 1.41 0.857 0.25 30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.537 86.1 5.89 2.56 0.09 31
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 0.744 178 3.51 2.69 0.21 32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.216 17.4 0.995 0.486 0.22 33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.107 9.11 0.884 0.354 0.12 33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.148 13.9 1.06 0.423 0.14 33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.254 18.5 2.13 0.714 0.12 33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.256 29.9 1.98 0.864 0.13 33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.560 39.2 2.94 2.73 0.19 33
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.186 15.2 4.93 0.537 0.04 34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2 21.1 151 10.4 92.6 2.03 35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH 30.7 152 15.6 114 1.97 36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2 5.20 150 138 20.3 0.04 37
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2 4.89 290 21.3 11.1 0.23 58
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 25.5 3.82 7.61 102 3.35 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2 32.5 5.85 2.53 94.6 12.85 16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2 22.2 12.7 16.6 125 1.34 20
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2 1.17 1.56 0.277 3.24 4.22 38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-b-Ala-Lys)-NH2 0.648 2.78 0.329 1.4 1.97 38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2 0.393 1.86 0.375 1.11 1.05 39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2 0.333 2.91 0.998 0.366 0.33 39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 0.461 2.45 0.931 1.37 0.50 40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 0.576 3.98 2.82 3.91 0.20 40
화합물 Ki
hMC1-R		 Ki
hMC3-R		 Ki
hMC4-R		 Ki
hMC5-R		 Ki
hMC1-R
/MC4-R		 서열번호
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 17.9 1.68 0.256 23.4 69.9 49
표 8 - 9: 선택 화합물의 방사능리간드 결합 분석 데이타
화합물 Ki hMC1-R Ki hMC3-R Ki hMC4-R Ki hMC5-R
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 49.9 9.00 0.569 218
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2 (서열번호 60) 11.9 38.1 5.70 11.8
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2 (서열번호 61) 3.46 16.6 6.65 4.88
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly
-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 62)		 0.614 5.09 2.31 3.23
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 62) 1.56 14.1 5.17 7.12
H-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 63) 1.10 1.58 6.00 0.629
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 64) 0.0868 0.751 0.0944 0.147
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 65) 1.66 4.80 0.250 9.62
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 66) 0.0452 0.298 0.169 0.386
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 67) 0.0808 0.396 0.0747 0.311
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 68) 4.41 4.23 0.455 12.9
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 1.25 0.661 0.292 5.94
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 71) 1.89 0.546 0.166 6.06
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 87.8 9.08 1.20 359
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 124 17.8 1.11 348
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 163 23.0 0.586 844
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 701) 0.144 0.352 0.0845 0.415
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg
-NH2 (서열번호 71) 		1.74 0.590 0.170 4.38
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 83) 3.86 4.97 0.192 38.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 73) 12.8 15.9 0.950 165
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg
-NH2 (서열번호 74)		 3.07 4.05 0.498 31.1
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-bAla-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH2 (서열번호 75) 0.792 0.570 0.162 4.18
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Gln-Arg-Arg-Arg-Arg-Arg-NH2 (서열번호 76) 0.726 0.474 0.209 5.12
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-Arg-Arg-Arg-Arg-Arg-
NH2 (서열번호 77)		 0.857 0.580 0.209 4.42
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Gln-Arg-
NH2 (서열번호 78)		 0.813 0.675 0.269 4.20
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Aib-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 79) 7.84 10.2 0.783 91.8
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 80) 2.93 9.07 0.293 59.0
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 80) 2.42 6.56 0.238 41.7
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 81) 6.66 19.3 0.819 88.8
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 82) 2.63 2.09 0.0737 11.6
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 82) 2.48 1.21 0.209 9.17
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 81) 3.65 2.26 0.261 12.1
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 83) 7.32 11.0 0.659 78.0
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 84) 4.11 7.26 0.302 48.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 283) 6.77 14.3 0.781 84.0
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Gln-Arg-Arg-NH2 (서열번호 2685) 3.04 3.22 0.230 3.85
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-Lys-Lys-Arg-Arg-Arg-Arg-Arg-NH2 (서열번호 86) 3.24 2.66 0.208 5.96
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Arg-Gln-NH2 (서열번호 87) 1.58 1.43 0.275 2.97
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 4.59 6.28 0.588 22.6
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 6.46 5.22 0.380 15.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 88) 4.62 5.68 0.505 45.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 89) 2.12 3.99 0.352 27.5
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 88) 3.41 0.975 0.549 11.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 90) 4.18 1.12 0.223 15.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 91) 2.71 0.732 0.202 5.53
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 92) 5.66 1.40 0.446 6.23
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (136) 0.211 0.665 0.635 118
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH2 (서열번호 137) 0.351 0.891 0.503 102
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 136) 0.209 0.699 0.596 137
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 138) 0.439 1.52 0.476 115
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 138) 0.821 2.50 0.700 148
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 139) 0.406 1.11 0.602 131
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-Arg-NH2 (서열번호 139) 1.27 4.63 1.51 220
화합물 Ki hMC1-R Ki hMC3-R Ki hMC4-R Ki hMC5-R
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 270) 2058 113 10.7 239
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 270) 1818 306 5.87 979
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 95) 1.75 1.74 0.15 16.8
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 96) 1.50 1.61 0.301 10.4
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 97) 1.81 2.08 0.305 19.3
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 92) 2.69 2.59 0.243 19.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 99) 2.25 0.62 0.303 2.77
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 101) 1.49 0.604 0.865 3.13
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 105) 3.28 1.95 0.575 15.5
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 100) 2.24 1.57 0.437 16.4
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 101) 2.14 1.12 0.624 11.9
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 102) 2.50 1.59 0.573 15.7
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 104) 3.00 1.70 0.442 15.5
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 103) 4.29 2.15 0.425 15.5
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 141) 0.410 0.837 0.246 56.3
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 142) 0.572 1.07 0.210 63.6
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 141) 0.475 0.800 0.196 53.8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 142) 0.779 1.21 0.293 56.0
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 143) 0.212 1.23 0.484 58.5
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 144) 0.778 1.22 0.468 47.0
표 10: 식 (V)의 화합물 예들의 결합 상수
식 (V) 화합물 Ki
hMC1		 Ki
hMC3		 Ki
hMC4		 Ki
hMC5
c[히단토인(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 271) 230 7590 126 7020
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2 (서열번호 276) 72.6 1920 45.2 >10000
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2 (서열번호 276) 60.4 2840 52.4 >10000
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2 (서열번호 276) 28 90.5 12.7 877
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2 (서열번호 276) 16.4 863 4.97 >10000
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2 (서열번호 273) 37.7 576 7.81 6400
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2 (서열번호 273) 66.6 1820 19.9 >10000
c[히단토인(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 200 68.8 6.63 142
c[히단토인(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 9028 2628 35.8 1156
c[히단토인(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 9938 2390 44.6 1103
c[히단토인(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 2170 1479 16.5 451
c[히단토인(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 1276 2756 266 1096
c[히단토인(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2 (서열번호 275) 7567 1922 420 2879
식 (VI) 화합물 예들의 결합 상수
식 (VI) 화합물 Ki
hMC1		 Ki
hMC3		 Ki
hMC4		 Ki
hMC5
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 14.3 198 5.76 67.8
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 11.9 311 5.41 73.9
히단토인(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 31.6 224 19.6 2500
히단토인(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 16.0 63.9 8.64 1820
히단토인(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 33.7 132 40.2 3210
히단토인(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 48.3 534 74.1 3290
히단토인(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 40.8 870 137 3560
히단토인(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) 17.7 73.6 8.40 2120
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 7.92 46.4 6.70 21.3
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 20.9 69.7 8.32 50.0
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 (서열번호 280) 12.9 38.5 3.53 27.1
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 (서열번호 280) 127 811 10.4 381
히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 13.9 38.4 5.73 18.9
히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 11.7 73.1 4.28 34.7
히단토인(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 36.8 290 13.7 133
히단토인(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 15.3 160 8.66 33.4
히단토인(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 11.6 194 11.5 28.9
히단토인(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 19.3 331 26.7 44.6
히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 9.49 124 2.95 2260
히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 287) 4.30 78.0 1.77 4540
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 8.59 94.1 2.44 7760
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 285) 5.68 55.5 2.44 4220
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 2.65 41.3 4.17 650
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 3.52 48.7 5.78 872
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 288) 3.51 29.2 6.04 914
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 286) 1.14 01.7 4.53 783
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 (서열번호 282) 11.9 7.43 0.195 14.6
식 (VII) 화합물 예들의 결합 상수
식 (VII) 화합물 Ki
hMC1		 Ki
hMC3		 Ki
hMC4		 Ki
hMC5
c[히단토인(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) 47.6 1100 47.1 >10000
c[히단토인(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) 21.2 730 34.5 >10000
c[히단토인(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) 47.4 1550 27.9 >10000
c[히단토인(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) 53.4 1760 41.6 >10000
c[히단토인(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) 38.5 1760 53.2 9270
c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 291) 15.6 305 8.92 3070
선택 화합물의 방사능리간드 결합 분석 데이타
화합물 Ki
hMC1-R		 Ki
hMC3-R		 Ki
hMC4-R		 Ki
hMC5-R
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 8.53 21.2 3.72 714
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 6.09 34.9 2.02 864
Ac-1-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 6.27 36.4 1.53 888
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 1.48 14.8 2.34 491
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 4.7 42 2.25 1470
Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 0.323 1.33 1.95 786
멜라노코르틴 기능적 활성 및 선택성
본 발명의 화합물은 다른 멜라노코르틴 수용체 대비 MC-4에 대해 선호적으로(즉, 선택적으로) 상호작용할 것이다. 선택성은, 화합물을 인간이나 그외 동물에게 투여하였을 때 이의 투여와 관련있는 다수의 부작용을 최소화하기 위해 특히 중요하다. 화합물의 MC-4 선택성은 본원에서 MC3에 대한 화합물의 EC50 에 대한 MC-1 수용체(EC50-MC-1)에 대한 화합물의 EC50 비, (EC50-MC-3)/MC-4 (EC50-MC-4)로 나타내며, EC50 값은 전술한 바와 같이 측정한다. 식은 다음과 같다:
MC -3 선택성 = [ EC 50 - MC -1]/[ EC 50 - MC -3]
MC -4 선택성 = [ EC 50 - MC -1]/[ EC 50 - MC -4]
상기 "MC-3-선택성" 비가 약 10 이상, 바람직하게는 약 100 이상, 보다 바람직하게는 약 500 이상이면, 화합물은 "MC-3 수용체에 대해 선택적"인 것으로 규정된다.
상기 "MC-4-선택성" 비가 약 10 이상, 바람직하게는 약 100 이상, 보다 바람직하게는 약 500 이상이면, 화합물은 "MC-4 수용체에 대해 선택적"인 것으로 규정된다.
당업자는 본원에 기술된 유사한 공정을 이용하여 본 발명의 화합물의 멜라노코르틴 수용체 분자에 대한 결합 활성을 분석할 수 있음을 알 것이다.
사이클릭 AMP 생분석
세포내 사이클릭 AMP(cAMP) 농도를 전자화학발광(ECL) 분석(Meso Scale Discovery®, Gaithersburg, MD; 이하 MSD라 함)으로 측정하였다. hMC 수용체 서브타입을 안정적으로 발현하는 CHO-K1 세포를 RMPI 1640® 분석 완충액(RMPI 1640 완충액은 0.5 mM 이소부틸메틸크산틴(IBMX) 및 0.2% 단백질 칵테일(MSD blocker A)을 포함함)에 현탁하였다. hMC 수용체 서브타입 1, 3, 4 또는 5를 안정적으로 발현하는 CHO-K1 형질전환주를, 통합형 탄소 전극이 장착되어 있으며 항-cAMP 항체로 코팅된 384웰 멀티-어레이®에 약 7,000 세포/웰의 밀도로 넣었다. 테스트 화합물을 농도를 증가시키면서 첨가하고, 세포를 약 40분간 약 37 ℃에서 배양하였다. 배양한 후, 0.2% 단백질 칵테일 및 2.5 nM TAGTM 루테늄-표지된 cAMP (MSD)이 함유된 라이시스 완충액(MgCl2 및 Triton X-100®이 첨가된 HEPES-완충화된 염수 용액, pH 7.3)을 첨가하여, 세포를 실온에서 약 90분간 배양하였다. 이차 배양한 후, 리딩 완충액(ECL 공-시약 및 X-100가 함유된 Tris-완충화된 용액, pH 7.8)을 첨가하고, Sector Imager 6000 reader®(MSD)를 이용한 ECL 검출에 의해 즉시 세포 라이세이트(cell lysate)에서의 cAMP 농도를 측정하였다. 데이타는 컴퓨터를 이용한 비선형 회귀 분석(XL fit; IDBS)으로 분석하였고, EC50 수치 또는 Kb 값 중 어느 하나로 기록하였다.
EC50은 최대 반응의 50%, 예컨대 전술한 분석으로 이용하여 결정된 cAMP의 최대 농도의 50%를 수득하는데 필요한 작용제 화합물의 농도이다. Kb 값은 길항제의 효능을 나타내며, Schild 분석에 의해 결정한다. 간략하게는, 길항제의 농도를 증가시키면서 작용제의 농도-반응 곡선을 구하였다. Kb 값은 작용제에 대한 농도-반응 곡선에서 2배수 변화(shift)를 만드는 길항제의 농도이다. 이는 Schild 플롯에서 y-축에서 0에 라인을 외삽하여 계산한다.
선택한 화합물을 상기 분석으로 테스트하고, 선택 화합물에 대한 cAMP 생분석 데이타는 표 14 - 25에 나타내었다.
표 14 - 17: 선택 화합물의 cAMP 바이오분석 데이타
화합물 EC50
hMC1-R		 EC50
hMC3-R		 EC50
hMC4-R		 EC50
hMC5-R		 EC50
hMC1-R/MC4-R		 서열번호
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 5.79 5.25 0.313 1630 18.0 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 6.17 5.6 0.397 1020 16.0 50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 26.5 10.5 0.493 2440 54.0 51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 8.43 32.4 0.959 2140 9.0 52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 4.23 8.09 0.719 23.2 6.0 52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 48.3 13.3 0.79 10000 61.0 51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 1.48 5.76 0.078 297 19.0 53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 1.39 2.89 0.055 467 25.0 53
ND = 검출 안됨
화합물 EC50
hMC1-R		 EC50
hMC3-R		 EC50
hMC4-R		 EC50
hMC5-R		 EC50
hMC1-R
/MC4-R		 서열번호
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 2.4 0.33 0.078 420 31 7
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-b-Ala-D-Cys)-Thr-NH2 0.35 1.1 0.11 0.37 3 24
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 0.31 0.27 0.018 3.1 17 27
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 0.28 0.24 0.028 3.9 10 32
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 0.37 0.1 0.021 1.7 18 34
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-b-Ala-Lys)-NH2 0.834 0.145 0.128 2.79 6.52 1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 0.76 0.199 0.0492 1.73 15.45 2
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 3.26 0.189 0.0949 30.2 34.35 6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 1.37 0.628 0.131 3.48 10.46 6
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 2.27 3.32 7.24 415 0.31 11
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ND 1.89 0.531 ND ND 21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 14.3 2.03 0.183 2240 78.14 22
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-b-Ala-D-Cys)-Thr-NH2 0.345 2.71 5376 2.38 0.06 24
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-b-Ala-D-Cys)-Thr-NH2 0.685 81.8 86.9 31.8 0.01 26
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2 0.931 3.22 1.65 >10000 0.56 28
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2 3.24 0.465 0.0915 78.5 35.41 30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2 0.819 0.541 0.453 45.3 1.81 30
ND = 검출 안됨
화합물 EC50 hMC1-R Kb hMC3-R Kb MC4-R EC50 hMC5-R 서열번호
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 17.6 12.4 38.8 11.8 16
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2 0.619 2.98 0.109 0.189 38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-b-Ala-Lys)-NH2 0.913 0.536 0.346 0.489 38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2 0.231 18.4 0.782 0.153 39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2 0.581 10.8 0.967 0.126 39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 0.413 9.32 0.824 0.307 40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 1.27 3.02 0.442 0.736 40
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2 383 61.5 53.6 2842 16
화합물 EC50 hMC1-R Kb hMC3-R Kb MC4-R EC50 hMC5-R 서열번호
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 193 5.72 1.58 1111 49
화합물 EC50 hMC1-R Kb hMC3-R Kb hMC4-R EC50 hMC5-R
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 66.1 33.4 0.687 6.84
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2 (서열번호 60) ND 4500 105 ND
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2 (서열번호 61) ND 395 16.8 ND
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 62) ND 207 18.5 ND
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 62) ND 220 4.07 ND
H-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 63) ND 261 3.11 ND
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 64) ND 14.1 22.8 ND
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 65) ND 233 26.0 ND
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 66) 1.39 16.2 7.94 0.839
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 67) 3.65 19.4 3.73 1.61
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 68) ND 17.7 1.49 ND
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 69) 6.3 70.0 1.66 38.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 69) 12.1 30.3 1.81 70.0
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 33.6 140 12.2 66.9
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 269 105 5.92 104
Ac-c Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 269) 690 70.7 4.56 177
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 70) 3.23 8.97 4.61 2.86
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 72) 52.0 170 6.14 328
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 73) 146 104 32.0 1400
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 74) 114 44.6 28.4 879
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Aib-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 79) 67.1 439 46.5 582
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 80) 144 116 8.93 819
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 80) 36.0 46.5 11.4 56.1
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 81) 93.0 71 15.9 > 10000
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 82) 39.7 30.9 6.66 501
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 82) 35.2 22.9 12.6 199
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 81) 29.1 13.6 13.4 204
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 83) 86.1 41.7 19.4 2360
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 84) 38.3 20.2 21.2 > 10000
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 83) 68.6 153 33.2 > 10000
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 88) 70.4 286 18.6 > 10000
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 89) 33.1 65.1 15.3 1720
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 88) 88.2 10.6 17.4 514
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 90) 58.7 39.3 10.3 460
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 91) 45.4 12.7 12.7 162
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 92) 309 22.8 17.1 570
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 139) 7.86 10.5 0.843 4900
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 29.7 25.6 7.37 82.9
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-bAla-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH2 (서열번호 75) 15.2 14.6 4.52 36.8
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Gln-Arg-Arg-Arg-Arg-Arg-NH2 (서열번호 76) 6.7 9.38 11.7 46.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-Arg-Arg-Arg-Arg-Arg-NH2 (서열번호 77) 7.9 41.7 10.9 62.4
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Gln-Arg-NH2 (서열번호 78) 16.9 36.0 7.12 58.9
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Gln-Arg-Arg-NH2 (서열번호 85) 16.4 20.8 7.31 44.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-Lys-Lys-Arg-Arg-Arg-Arg-Arg-NH2 (서열번호 86) 12.0 13.7 9.38 54.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Arg-Gln-NH2(서열번호 87) 7.5 12.2 7.61 51.7
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 43.3 215 5.87 1286
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 71) 37.9 112 41.1 1798
ND = 검출 안됨
화합물 EC 50 hMC1 -R EC 50 hMC3 -R EC 50 hMC4 -R EC 50 hMC5 -R
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 136) 4.70 4.56 0.634 147
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH2 (서열번호 137) 5.90 7.73 1.02 2890
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 136) 0.481 7.32 0.964 2010
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 138) 7.15 9.37 1.25 1570
화합물 EC 50 hMC1 -R Kb hMC3 -R Kb hMC4 -R EC 50 hMC5 -R
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 270) ND ND ND ND
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-Pro-Pro-Lys-Asp-NH2 (서열번호 270) 770 221 4.52 869
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 95) 29 22.6 16.7 173
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 96) 102 26.3 14.6 261
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 97) 26.6 101 9.34 351
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 92) 45.5 181 6.35 149
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 99) 23.7 9.22 5.87 39.7
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 101) 34.7 15.0 8.68 28.2
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 105) 19.1 106 4.59 100
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 100) 19.8 37.8 8.43 158
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 101) 11.2 52.1 9.45 95.7
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 102) 33.8 93.6 4.42 89.5
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2(서열번호 104) 232 68.8 10.0 250
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 103) 32.2 98.3 5.23 194
ND = 검출 안됨
화합물 EC 50 hMC1 -R EC 50 hMC3 -R EC 50 hMC4 -R EC 50 hMC5 -R
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 141) 5.66 4.70 0.422 1551
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 142) 7.57 4.18 0.600 1792
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 141) 2.36 2.74 0.260 500
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 142) 2.81 3.29 0.298 566
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 143) 1.86 1.39 0.367 165
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH2 (서열번호 144) 2.06 1.61 0.394 199
표 22 - 24: 식 (I) 화합물 예들의 세포내 사이클릭 AMP ( cAMP )의 농도
식 (V) 화합물 EC50
hMC1		 EC50
hMC3		 EC50
hMC4		 EC50
hMC5
c[히단토인(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 271) - 218 5.42 -
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2 (서열번호 276) - 22.3 3.62 -
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2 (서열번호 276) - 39.2 4.94 -
c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2 (서열번호 276) 56.7 18.2 0.182 >10000
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2 (서열번호 273) 56.6 88.6 4.50 9300
c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2 (서열번호 273) - 49.3 2.12 -
식 (VI) 화합물 EC50
hMC1		 EC50
hMC3		 EC50
hMC4		 EC50
hMC5
히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 54.3 12.2 0.177 >10000
히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 124 8.05 0.214 >10000
히단토인(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) - 4.89 1.80 -
히단토인(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) - 2.56 1.47 -
히단토인(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) - 4.61 0.977 -
히단토인(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) - 9.68 1.83 -
히단토인(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 284) - 9.97 13.9 -
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 14.2 2.46 0.336 201
히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 (서열번호 280) 17.0 21.5 0.584 352
히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 (서열번호 280) 40.2 8.90 0.495 8300
히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 17.6 2.23 0.241 516
히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 4.70 2.22 0.309 355
히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 18.0 17.1 0.160 2710
히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 287) 12.9 10.3 0.125 7440
히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 8.83 7.86 0.0979 4010
히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 285) 9.97 3.63 0.0687 335
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 8.81 18.2 0.503 3560
히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 279) 11.5 23.2 0.513 3950
히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 288) 7.53 11.6 0.435 9840
히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 286) 8.85 5.17 0.599 3610
히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 (서열번호 282) 96.6 13.1 21.2 103
식 (VII) 화합물 EC50
hMC1		 EC50
hMC3		 EC50
hMC4		 EC50
hMC5
c[히단토인(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) - 6.28 0.407 -
c[히단토인(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) - 3.77 0.214 -
c[히단토인(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) - 4.72 0.428 -
c[히단토인(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) - 8.51 1.85 -
c[히단토인(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 290) - 5.66 1.72 -
c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2 (서열번호 291) 14.5 21.8 0.576 1780
선택 화합물의 cAMP 바이오분석 데이타
화합물 EC50
hMC1-R		 EC50
hMC3-R		 EC50
hMC4-R		 EC50
hMC5-R
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 6.42 2.39 0.194 1540
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 9.66 6.11 0.275 1730
Ac-1-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 8.67 4.21 0.363 1320
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 292) 5.78 3.95 0.219 2580
생체내 연구
본 발명의 화합물은 하기 과정에 따라 인슐린 내성 및/또는 체중에 대한 효과를 테스트할 수 있으며, 테스트하였다. 당업자라면 본원에 기재된 방법과 유사한 방법을 이용하여 인슐린 내성 및/또는 체중에 대한 본 발명의 화합물의 효과를 분석할 수 있음을 알 것이다.
생체내 분석에서 조사한 멜라노코르틴 수용체를 활성화하는 리간드 화합물은 다음과 같다(표 26).
리간드 코드 구조
화합물 A Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 50)
화합물 B 히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278)
단기 급식 실험(금식)
Sprague Dawley 수컷 랫(250g)을 각각의 케이지에서 넣어, 12:12 시간의 주:야 조건하에 유지시켰다. 랫은 실험을 개시하기 전에 18시간동안 절식시켰으며 물을 자유롭게 식이가능하게 하였다. 0 시간에, 랫에 선택 화합물을 선정한 투여량 100 nmole/kg으로 또는 비히클을 피하(sc) 주사하고, 음식물을 제공하였다. 개별 음식물 섭취량은 주사 후 약 2, 4 및 6시간에 측정하였다. 본 발명의 선택 화합물의 데이타는 도 1에 나타낸다.
장기 급식 실험
실험하기 전 10주간 정상 식이(300g; Research Diets 12450) 또는 고지방 식이(400g; Research Diet 12451)를 제공한, Sprague Dawley 수컷 랫을, 각각의 케이지에서 넣어, 12:12 시간의 주:야 조건하에 유지시고, 음식물과 물을 자유롭게 식이가능하게 하였다. 랫을 마취시키고, 삼투 미니 펌프(Alzet, Cupertino, CA)를 이용하여 피하 이식하였다. 펌프는 화합물 A 또는 화합물 B를 75, 300 또는 1200 nmole/kg/day으로, 또는 비히클을 7일간 전달하였다. 각각의 체중과 음식물 섭취량을 매일 측정하였다.
7일째에, 랫을 마취하고, 경구 우측 동맥 캐뉼러를 끼웠다. 8일에, iv 글루코스 내성 테스트를 수행하였고, 혈액 샘플을 헤파린 처리한 시린지로 -10 및 0 시간에 채혈하였다. 0시간대 혈액 샘플을 채혈한 후 바로, 랫에게 내재 캐뉼러를 통해 글루코스(1g/kg)을 주입하였다. 이후, 혈액 샘플을 2.5, 5, 10, 20 및 40분 후에 채혈하였다. 혈장내 글루코스(Diagnostic Chemicals Limited) 및 인슐린(Alpco) 수준을 통상적인 시판 키트로 결정하였다. 그 결과는 도 2A-D 및 3A-D에 나타낸다.
글루코스 내성 테스트
실험하기 전 12주간 정상 식이(30g; Research Diets 12450) 또는 고지방 식이(45g; Research Diet 12452)를 제공한, Sprague Dawley 수컷 랫을, 각각의 케이지에서 넣어, 12:12 시간의 주:야 조건하에 유지시고, 음식물과 물을 자유롭게 식이가능하게 하였다. 랫을 마취하고, 삼투 미니 펌프(Alzet, Cupertino, CA)를 이용하여 피하 이식하였다. 펌프는 화합물 A를 200, 600 또는 1800 nmole/kg/day로, 또는 비히클을 14일간 전달하였다. 14일째에, 랫을 18시간 또는 밤새 금식시켰다. 15일에, 랫에 글루코스(2g/kg)를 복막내 주입하여 글루코스 내성을 테스트하였다. 글루코스 주입 후, 0, 15, 30, 60 및 180 분에, 혈액 샘플을 꼬리에서 채혈하여, Accu-Chek 글루코스 측정기로 혈당을 측정하였다. 결과는 도 4에 나타낸다.
수컷 Lepob/Lepob 마우스(50g)를 12:12시간의 주야 주시 조건 하에 그룹 사육하고, 음식물과 물을 자유롭게 섭취할 수 있도록 하였다. 마우스를 18시간 또는 밤새 금식시킨 다음, 복막내 글루코스 내성 테스트를 수행하였다. -15분에, 마우스에 화합물 A를 6.4 μole/kg 투여량으로 복막내 주입하고, 혈액 샘플을 꼬리에서 채혈하였다. 0시간에, 마우스에 글루코스(1g/kg)를 복막내 주입하고, 0, 15, 30, 60 및 90분 후에 꼬리에서 혈액 샘플을 채혈하고, 혈당을 Glucometer Elite XL (Bayer Corporation)로 측정하였다. 결과는 도 5에 나타낸다.
투여 및 용도
본 발명의 펩타이드는 약학적으로 하용가능한 염 형태로 제공될 수 있다. 그러한 염의 예로는, 유기산(예, 아세트산, 락트산, 말레산, 시트르산, 말산, 아스코르브산, 숙신산, 벤조산, 메탄설폰산, 톨루엔설폰산 또는 파모산), 무기산(예, 염산, 황산, 또는 인산) 및 폴리머산(예, 탄닌산, 카르복시메틸 셀룰로스, 폴리락트산, 또는 폴리락트산-글리콜산의 공중합체)과 형성된 염이 있으나, 이로 한정되는 것은 아니다. 본 발명의 펩타이드 염을 제조하는 전형적인 방법은 당업계에 잘 알려져 있으며, 표준적인 염 교환 방법에 의해 달성될 수 있다. 따라서, 본 발명의 펩타이드의 TFA 염(분취용 HPLC 및 TFA가 함유된 완충액에 의한 용출로, 펩타이드 정제하여 수득되는 TFA 염)은, 0.25 N 아세트산 수용액 소량에 펩타이드를 용해시킴으로써, 아세테이트 염과 같은 다른 염으로 변환시킬 수 있다. 수득되는 용액은 세미-분취용 HPLC 컬럼(Zorbax®, 300 SB, C-8)에 적용한다. 컬럼은, (1) 0.1 N 암모늄 아세테이트 수용액으로 0.5시간; (2) 0.25 N 아세트산 수용액으로 0.5시간; 및 (3) 유속 4 ml/min로 선형 농도 구배(용액 B를 30분간 20%에서 100%로 농도 구배(용액 A는 0.25 N 아세트산 수용액이고, 용액 B는 아세토니트릴/물, 80:20 중의 0.25 N 아세트산 수용액임)로 용출시킨다.
당업자들에게 잘 알려져 있는 바와 같이, 멜라노코르틴 수용체(MC-R) 작용제 또는 길항제 활성을 가질 펩타이드의 공지된 용도 및 잠재적인 용도는 다양하고 다채로워, 작용제 작용을 도출하기 위한 목적으로 본 발명의 화합물을 투여하면 멜라노코르틴 그 자체와 동일한 효과 및 용도를 가질 수 있다.
따라서, 본 발명은 활성 성분으로서 식 (I)의 화합물 1종 이상을 약학적으로 허용가능한 담체와 조합하여 포함하는, 약학 조성물을 포함한다.
본 발명의 조성물에서 활성 성분의 투여량은 다양할 수 있지만, 활성 성분의 양은 적합한 투약 형태를 수득할 수 있어야 한다. 선택되는 투여량은 원하는 치료 효과, 투여 경로 및 치료 기간에 따라 결정된다. 대게, 본 발명의 활성에 있어 유효량은 1x10-7 내지 200 mg/kg/day, 바람직하기로는 1x10-4 내지 100 mg/kg/day이며, 이는 단일 투약으로서 투여하거나 또는 다중 투약으로 분할하여 투여할 수 있다.
본 발명의 화합물은 경구, 비경구(예, 근육내, 복막내, 정맥내 또는 피하내 주입 또는 이식), 비내, 질, 직장, 설하 또는 국소 투여 경로에 의해 투여될 수 있으며, 각 투여 경로에 적합한 투약 형태를 제공하기 위해 약제학적으로 허용가능한 담체와 함께 제형화될 수 있다.
경구 투여를 위한 고형의 투약 형태로는, 캡슐제, 정제, 환제(pills), 산제 및 과립제를 포함한다. 상기 고형의 투약 형태에서, 활성 화합물은 하나 이상의 약학적으로 허용가능한 불활성 담체, 예컨대 자당, 유당 또는 전분과 혼합된다. 상기 투약 형태는 또한 통상 실시되는 바와 같이, 상기한 불활성 희석제 이외의 부가적인 물질, 예컨대 마그네슘 스테아레이트와 같은 윤활제를 포함할 수 있다. 캡슐제, 정제 및 환제의 경우, 투약 형태는 또한 완충제를 포함할 수도 있다. 정제와 환제는 부가적으로 장내 코팅형태(entteric coating)로 제조될 수 있다.
경구 투여를 위한 액상 투약 형태는, 약학적으로 허용가능한 유제, 액제, 현탁제, 시럽제, 물과 같이 당해분야에서 일반적으로 사용되는 불활성의 희석제를 함유하는 엘릭실제를 포함한다. 이러한 불활성의 희석제 이외에, 조성물은 또한 습윤제, 유화제, 현탁제, 감미제, 향미제 및 향료와 같은 보강제(adjuvant)를 더 포함할 수 있다.
본 발명의 비경구 투여용 조제물은, 무균 수용액 또는 비수성 용액, 현탁제 또는 유제를 포함한다. 비수성 용액 또는 비히클의 예로는, 프로필렌 글리콜, 폴리에틸렌 글리콜, 올리브 오일 및 옥수수 오일과 같은 식물성 오일, 젤라틴 및 에틸 올레이트와 같은 주사가능한 유기 에스테르를 포함한다. 이러한 투약 형태는 또한 보존제, 습윤제, 유화제 및 분산제와 같은 보강제를 포함할 수 있다. 이는, 예컨대 박테리아 체류 필터를 통한 여과, 조성물내 멸균제 첨가, 조성물에 방사선 조사 또는 조성물의 열처리에 의해 멸균시킬 수도 있다. 또한, 이는 사용하기 바로 전에 멸균수 또는 주입가능한 기타 멸균 매질에 용해될 수 있는 고형의 멸균 조성물의 형태로 제조될 수 있다.
직장 또는 질 투여용 조성물은 바람직하기로는 활성 성분과 더불어 코코아 버터나 좌제 왁스와 같은 부형제를 포함할 수도 있는 좌제이다.
비내 또는 설하 투여용 조성물은 또는 당해분야에 잘 알려진 표준적인 부형제가 부가된 형태로 제조된다.
또한, 본 발명의 화합물은 하기 특허 및 특허 출원에 개시된 바와 같이 서방형 조성물 형태로 투여될 수 있다. 미국 특허 제 5,672,659호에는, 생활성제와 폴리에스테르로 구성된 서방형 조성물이 개시되어 있다. 미국 특허 제 5,595,760호에는 생활성제로 구성된 젤 형태의 서방형 조성물이 개시되어 있다. 미국 특허 제 5,821,221호에는 생활성제 및 키토산으로 구성된 폴리머성 서방형 조성물이 개시되어 있다. 미국 특허 제 5,916,883호에는 생활성제 및 사이클로덱스트린으로 구성된 서방형 조성물이 개시되어 있다. 이러한 특허 및 출원의 내용은 원용에 의해 본 명세서에 포함된다.
SEQUENCE LISTING <110> SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES S.A.S. BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURE AND MECHANICAL COLLEGE Halem, Heather Culler, Michael Butler, Andrew <120> USE OF MELANOCORTINS TO TREAT INSULIN SENSITIVITY <130> 183P/PCT2 <150> US 61/001933 <151> 2007-11-05 <160> 293 <170> PatentIn version 3.5 <210> 1 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala or 1-amino-1-cyclohexanecarboxylic acid (A6c) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 1 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 2 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 6-aminohexanoic acid (Ahx) or 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 2 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 3 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 3 Xaa Cys His Xaa Arg Trp Xaa Xaa Thr 1 5 <210> 4 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 4 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 5 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = 1-amino-1-cyclohexanecarboxylic acid (A6c) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 5 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 6 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal), beta-cyclohexylAla (Cha) or Nle, all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 6 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 7 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric acid (Aib) or Gly <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 7 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 8 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = Ala, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric acid (Aib) or Gly <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 8 Xaa Xaa Xaa His Xaa Arg Trp Cys 1 5 <210> 9 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric acid (Aib) or Gly <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 9 Xaa Cys Xaa His Xaa Arg Trp Xaa 1 5 <210> 10 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = Ala, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba) or alpha-aminoisobutyric acid (Aib) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 10 Xaa Xaa Xaa His Xaa Arg Trp Xaa 1 5 <210> 11 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = octahydroindole-2-carboxylic acid (Oic), cyclohexylGly (Chg), homo-cyclohexylAla (hCha), D-Cha,nipecotic acid (Nip), hPro, hLeu, Phe, D-Phe, D-Chg, hPhe, beta-homoMet, or 4-aminobutyric acid (Gaba), all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 11 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 12 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = beta-cyclohexylAla (Cha) modified with n-butanoyl <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 12 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 13 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = beta-cyclohexylAla (Cha), homo-cyclohexylAla (hCha), Leu, homo-Leu (hLeu) or Phe, all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 13 Xaa Asp His Xaa Arg Xaa Ala Lys 1 5 <210> 14 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), 7-aminoheptanoic acid (Aha) or 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 14 Xaa Asp His Xaa Arg Xaa Xaa Lys 1 5 <210> 15 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn), 4-aminobutyric acid (Gaba), 6-aminohexanoic acid (Ahx), beta-Ala, or D-Ala <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 15 Xaa Cys His Xaa Arg Xaa Xaa Cys 1 5 <210> 16 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Trp, beta-(2-naphthyl)Ala (2-Nal) or beta-(1-naphthyl)Ala (1-Nal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 16 Xaa Cys Xaa His Xaa Arg Xaa Cys 1 5 <210> 17 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with n-butanoyl <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or Trp <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 17 Xaa Cys Xaa His Xaa Arg Xaa Cys 1 5 <210> 18 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylAla (Bal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 18 Xaa Cys Xaa His Xaa Arg Xaa Cys 1 5 <210> 19 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = D-Ala <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 19 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 20 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-beta-2-naphthylAla (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 20 Xaa Cys Xaa His Xaa Arg Xaa Cys 1 5 <210> 21 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 21 Xaa Xaa Xaa His Xaa Arg Trp Cys 1 5 <210> 22 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = Cys or penicillamine (Pen) <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 22 Xaa Xaa Xaa His Xaa Arg Trp Xaa 1 5 <210> 23 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 23 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr 1 5 <210> 24 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = Arg or homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 24 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr 1 5 <210> 25 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 25 Xaa Cys His Xaa Arg Xaa Xaa Xaa Thr 1 5 <210> 26 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe or D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 26 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr 1 5 <210> 27 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 27 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 28 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Trp or 3-benzothienylAla (Bal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 28 Xaa Asp Xaa His Xaa Arg Xaa Lys 1 5 <210> 29 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) or Cys <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 29 Xaa Cys Xaa His Xaa Arg Trp Xaa 1 5 <210> 30 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-alpha-aminobutyric acid (D-Abu), D-Val, D-Ile, D-Leu, D-tert-Leu (D-Tle) or D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 30 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 31 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 31 Xaa Xaa His Xaa Arg Trp Xaa Cys 1 5 <210> 32 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = Cys or penicillamine (Pen) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 32 Xaa Xaa His Xaa Arg Trp Xaa Xaa 1 5 <210> 33 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Leu, beta-cyclohexylAla (Cha), Ile, Phe, Val or beta-(2-naphthyl)Ala (2-Nal), all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 33 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 34 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle or Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 34 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 35 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = beta-(3-pyridiyl)Ala (3-Pal) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 35 Xaa Cys Xaa Xaa Arg Trp Xaa Cys 1 5 <210> 36 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 36 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 37 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 37 Xaa Cys His Phe Arg Xaa Xaa Cys 1 5 <210> 38 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Ala or beta-Ala <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 38 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 39 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) or 6-aminohexanoic acid (Ahx) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 39 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 40 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-Phe (hPhe) or beta-cyclohexylAla (Cha), both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 40 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 41 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala or 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 41 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 42 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 6-aminohexanoic acid (Ahx) or 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 42 Xaa Cys His Xaa Arg Trp Xaa Cys 1 5 <210> 43 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MOD_RES <222> (9)..(9) <223> C-terminus is the free acid <400> 43 Xaa Cys His Xaa Arg Trp Xaa Xaa Thr 1 5 <210> 44 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = beta-cyclohexylAla (Cha), Nle, cyclohexylGly (Chg), D-Cha, homo-cyclohexylAla (hCha), D-Chg or homo-Phe (hPhe), all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 44 Xaa Asp His Xaa Arg Trp Xaa Lys 1 5 <210> 45 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba), 6-aminohexanoic acid (Ahx), beta-Ala or D-Ala <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 45 Xaa Cys His Xaa Arg Xaa Xaa Cys 1 5 <210> 46 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Trp, beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylalanine (Bal) <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 46 Xaa Cys Xaa His Xaa Arg Xaa Cys 1 5 <210> 47 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 47 Xaa Xaa Xaa His Xaa Arg Trp Cys 1 5 <210> 48 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (8)..(8) <223> C-terminus is the free acid <400> 48 Xaa Cys His Xaa Arg Trp Xaa Xaa 1 5 <210> 49 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 49 Arg Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 50 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Arg or D-Arg, both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 50 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 51 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Arg or Arg, both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 51 Xaa Cys Xaa His Xaa Arg Trp Xaa 1 5 <210> 52 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Arg or Arg, both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 52 Xaa Cys His Xaa Arg Trp Xaa Xaa 1 5 <210> 53 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Arg or Arg, both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 53 Xaa Asp His Xaa Arg Trp Ala Lys 1 5 <210> 54 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(9) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = Gly, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba) or 5-aminopentanoic acid (Apn) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 54 Xaa Cys Xaa His Xaa Arg Trp Xaa Cys 1 5 <210> 55 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = Trp or beta-(2-naphthyl)alanine (2-Nal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 55 Cys Glu His Xaa Arg Xaa Ala Cys 1 5 <210> 56 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = Trp or beta-(2-naphthyl)Ala (2-Nal) <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 56 Cys Xaa His Xaa Arg Xaa Ala Cys 1 5 <210> 57 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(9) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 57 Xaa Cys Xaa His Xaa Arg Trp Xaa Cys 1 5 <210> 58 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(9) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 58 Xaa Asp Xaa His Xaa Arg Xaa Ala Lys 1 5 <210> 59 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> Cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Glu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 59 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 60 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (12)..(12) <223> Xaa = Nle <220> <221> DOMAIN <222> (13)..(18) <223> cyclic <220> <221> MISC_FEATURE <222> (15)..(15) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 60 Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Xaa Asp His Xaa Arg 1 5 10 15 Trp Lys <210> 61 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (12)..(12) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = Nle <220> <221> DOMAIN <222> (14)..(19) <223> cyclic <220> <221> MISC_FEATURE <222> (16)..(16) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 61 Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Xaa Xaa Asp His Xaa 1 5 10 15 Arg Trp Lys <210> 62 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle or Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 62 Xaa Asp His Xaa Arg Trp Lys Xaa Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 63 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 63 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Lys Lys Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 64 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 64 Xaa Asp His Xaa Arg Trp Lys Pro Pro Lys Asp Tyr Gly Arg Lys Lys 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 65 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 65 Cys Glu His Xaa Arg Trp Gly Cys Pro Pro Lys Asp Tyr Gly Arg Lys 1 5 10 15 Lys Arg Arg Gln Arg Arg Arg 20 <210> 66 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 66 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Lys Lys Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 67 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (12)..(12) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 67 Xaa Asp His Xaa Arg Trp Lys Pro Pro Lys Asp Xaa Tyr Gly Arg Lys 1 5 10 15 Lys Arg Arg Gln Arg Arg Arg 20 <210> 68 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 68 Cys Glu His Xaa Arg Trp Gly Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Gln Arg Arg Arg 20 <210> 69 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala or 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 69 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Gln Arg Arg Arg 20 <210> 70 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 70 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Lys Lys Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 71 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 71 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Gln Arg Arg Arg 20 <210> 72 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 72 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 73 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 73 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 74 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 74 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg 20 <210> 75 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 75 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Gln Arg Arg Arg Arg 20 <210> 76 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 76 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Gln Arg Arg Arg Arg Arg 20 <210> 77 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 77 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Gln Lys Arg Arg Arg Arg Arg 20 <210> 78 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 78 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Arg Gln Arg 20 <210> 79 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (15)..(15) <223> Xaa = alpha-aminoisobutyric acid (Aib) <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 79 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Xaa Arg 1 5 10 15 Lys Lys Arg Arg Gln Arg Arg Arg 20 <210> 80 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Arg or Lys <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 80 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 81 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) or beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 81 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 82 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Arg or Lys <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 82 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 83 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Arg or Lys <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 83 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 84 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 84 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Arg Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 85 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 85 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Gln Arg Arg 20 <210> 86 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 86 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Gln Lys Lys Arg Arg Arg Arg Arg 20 <210> 87 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 87 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Arg Arg Gln 20 <210> 88 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) or beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 88 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 89 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 89 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 90 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 90 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Lys Arg Arg Gln Arg Arg Arg 20 <210> 91 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 91 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg 1 5 10 15 Lys Arg Arg Gln Arg Arg Arg 20 <210> 92 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 92 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Lys 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 93 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 93 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 94 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 94 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 95 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 95 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Lys Arg Arg Gln Arg Arg Arg 20 <210> 96 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 96 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Arg Arg Arg Gln Arg Arg Arg 20 <210> 97 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 97 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg 1 5 10 15 Lys Arg Arg Gln Arg Arg Arg 20 <210> 98 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 98 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 99 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 99 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 100 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 100 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Lys Arg Arg Gln Arg Arg Arg 20 <210> 101 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 101 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Arg Arg Arg Gln Arg Arg Arg 20 <210> 102 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 102 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg 1 5 10 15 Lys Arg Arg Gln Arg Arg Arg 20 <210> 103 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 103 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Lys 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 104 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 104 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 105 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 105 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 106 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 106 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Gln Arg Arg Arg Arg 20 <210> 107 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 107 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Gln Arg Arg Arg Arg Arg 20 <210> 108 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 108 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Gln Lys Arg Arg Arg Arg Arg 20 <210> 109 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 109 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Gln Lys Lys Arg Arg Arg Arg Arg 20 <210> 110 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 110 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Gln Arg Arg 20 <210> 111 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 111 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Arg Gln Arg 20 <210> 112 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 112 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg 1 5 10 15 Lys Lys Arg Arg Arg Arg Arg Gln 20 <210> 113 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 113 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 114 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 114 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg 20 <210> 115 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 115 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 116 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 116 Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg Arg 20 25 <210> 117 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 117 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 118 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 118 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 119 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 119 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 120 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 120 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg 20 <210> 121 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 121 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg Arg 20 25 <210> 122 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(1-naphthyl)Ala (1-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 122 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Arg Gln Arg Arg Arg 20 25 <210> 123 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 123 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 124 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 124 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 125 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 125 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 126 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 126 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg 20 <210> 127 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 127 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Arg Gln Arg Arg Arg 20 25 <210> 128 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 128 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg Arg 20 25 <210> 129 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 129 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 130 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 130 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 131 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 131 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 132 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 132 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg 1 5 10 15 Arg Arg Arg Gln Arg Arg Arg 20 <210> 133 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (24)..(24) <223> AMIDATION <400> 133 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg 20 <210> 134 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 134 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Gln Arg Arg Arg Arg 20 25 <210> 135 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 3-benzothienylAla (Bal) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Lys or Arg <220> <221> MISC_FEATURE <222> (13)..(13) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (25)..(25) <223> AMIDATION <400> 135 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg 1 5 10 15 Arg Arg Arg Arg Arg Gln Arg Arg Arg 20 25 <210> 136 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 136 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Lys Lys Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 137 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 137 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Tyr Gly Arg Lys Lys Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 138 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 138 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 139 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 139 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 140 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 140 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Gly Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 141 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 141 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Lys Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 142 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 142 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Lys Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 143 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 143 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Arg Arg Lys Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 144 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 144 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Arg Lys Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 145 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 145 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Tyr Gly Arg Lys Lys Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 146 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 146 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Tyr Gly Arg Lys Lys Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 147 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 147 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 148 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 148 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 149 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 149 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 150 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 150 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 151 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 151 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 152 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 152 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 153 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 153 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 154 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 154 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 155 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 155 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 156 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 156 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 157 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 157 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 158 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 158 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 159 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 159 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 160 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 160 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 161 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 161 Xaa Asp His Xaa Arg Trp Ala Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 162 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 162 Xaa Asp His Xaa Arg Trp Ala Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 163 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 163 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 164 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 164 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 165 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 165 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 166 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 166 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Gly Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 167 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 167 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 168 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 168 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 169 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 169 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg Arg <210> 170 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 170 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 171 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 171 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 172 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 172 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg Arg <210> 173 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 173 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 174 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 174 Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 175 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 175 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 176 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 176 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 177 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 6-aminohexanoic acid (Ahx) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 177 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 178 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 6-aminohexanoic acid (Ahx) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 178 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 179 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 179 Xaa Cys His Xaa Arg Trp Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 180 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 180 Xaa Cys His Xaa Arg Trp Xaa Xaa Thr Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 181 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 181 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 182 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 182 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 183 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = beta-cyclohexylAla (Cha), homo-cyclohexylAla (hCha), or Nle, all modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 183 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 184 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = beta-cyclohexylAla (Cha) or homo-cyclohexylAla (hCha), both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 184 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 185 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle or cyclohexylGly (Chg), both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 185 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 186 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = cyclohexylGly (Chg) or homo-cyclohexylAla (hCha), both modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 186 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 187 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 187 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 188 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 188 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 189 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 189 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 190 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 190 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 191 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 191 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 192 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 192 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 193 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 193 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 194 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-cyclohexylAla (hCha) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 194 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 195 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-cyclohexylGly (D-Chg) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 195 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 196 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-cyclohexylGly (D-Chg) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 196 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 197 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-phenylAla (hPhe) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 197 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 198 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = homo-phenylAla (hPhe) modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 198 Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 199 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) or 6-aminohexanoic acid (Ahx) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 199 Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 200 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) or 6-aminohexanoic acid (Ahx) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 200 Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 201 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 201 Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 202 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Trp <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 202 Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 203 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 203 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 204 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 204 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 205 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 205 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 206 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 206 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 207 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 207 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 208 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = penicillamine (Pen) <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 208 Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 209 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 209 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 210 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (18)..(18) <223> AMIDATION <400> 210 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg <210> 211 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 211 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln Arg 1 5 10 15 Arg Arg Arg <210> 212 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 212 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 213 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Gly or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 213 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 214 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 214 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 215 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = Tyr or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 215 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 216 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 216 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 217 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 217 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 218 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 218 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 219 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 219 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 220 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 220 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 221 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 221 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 222 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 222 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 223 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 223 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 224 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (23)..(23) <223> AMIDATION <400> 224 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg Arg 20 <210> 225 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 225 Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg Arg 20 <210> 226 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 226 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 227 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 227 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 228 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 228 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 229 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 229 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 230 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 230 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 231 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(11) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 231 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg 1 5 10 15 Arg Arg Gln Arg Arg Arg 20 <210> 232 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = homo-Arg (hArg) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = 4,4'-biphenylAla (Bip) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (11)..(11) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 232 Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg 1 5 10 15 Gln Arg Arg Arg 20 <210> 233 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 233 Xaa Cys Xaa His Xaa Arg Trp Gly Cys Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 234 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 234 Xaa Cys Xaa His Xaa Arg Trp Gly Cys Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 235 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 235 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 236 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 236 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 237 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 237 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 238 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 238 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 239 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 239 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 240 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 240 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 241 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 241 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 242 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 5-aminopentanoic acid (Apn) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 242 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 243 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 243 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 244 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 244 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 245 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 245 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 246 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 246 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 247 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 247 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 248 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 248 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 249 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 249 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 250 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Leu <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 250 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 251 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 251 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 252 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 252 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 253 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 253 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 254 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 254 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 255 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 255 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 256 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 256 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 257 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 257 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 258 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle modified with acyl (Ac) <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-cyclohexylAla (D-Cha) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 258 Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 259 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 259 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 260 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 260 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 261 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 261 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 262 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = beta-Ala or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 262 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 263 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (21)..(21) <223> AMIDATION <400> 263 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg 20 <210> 264 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (19)..(19) <223> AMIDATION <400> 264 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg <210> 265 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (22)..(22) <223> AMIDATION <400> 265 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg 1 5 10 15 Arg Gln Arg Arg Arg Arg 20 <210> 266 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Nle <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = 4-aminobutyric acid (Gaba) <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) <220> <221> MISC_FEATURE <222> (10)..(10) <223> Xaa = 8-amino-3,6-dioxaoctanoic acid (Doc) or absent <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 266 Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 267 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Phe <220> <221> DOMAIN <222> (2)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-(Et)Tyr <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala <220> <221> MISC_FEATURE <222> (8)..(8) <223> Xaa = D-Cys <220> <221> MISC_FEATURE <222> (9)..(10) <223> Xaa = beta-Ala <220> <221> MOD_RES <222> (20)..(20) <223> AMIDATION <400> 267 Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln 1 5 10 15 Arg Arg Arg Arg 20 <210> 268 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-4-bromo-phenylAla (D-4-Br-Phe) <220> <221> MOD_RES <222> (12)..(12) <223> AMIDATION <400> 268 Cys Glu His Xaa Arg Trp Gly Cys Pro Pro Lys Asp 1 5 10 <210> 269 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = Trp, beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylAla (Bal) <220> <221> MOD_RES <222> (12)..(12) <223> AMIDATION <400> 269 Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp 1 5 10 <210> 270 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with acyl (Ac) <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal) <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = beta-(2-naphthyl)Ala (2-Nal) <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = beta-Ala or alpha-aminoisobutyric acid (Aib) <220> <221> MOD_RES <222> (12)..(12) <223> AMIDATION <400> 270 Cys Glu His Xaa Arg Xaa Xaa Cys Pro Pro Lys Asp 1 5 10 <210> 271 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(7) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Cys or homocyteine (hCys) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (7)..(7) <223> AMIDATION <400> 271 Xaa Xaa His Xaa Arg Trp Cys 1 5 <210> 272 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(7) <223> Cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Cys or homocysteine (hCys) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (7)..(7) <223> AMIDATION <400> 272 Xaa Xaa His Xaa Arg Trp Cys 1 5 <210> 273 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(7) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Lys, ornithine (Orn), 2,4-diaminobutyric acid (Dab), or 2,3-diaminopropionic acid (Dap) <220> <221> MOD_RES <222> (7)..(7) <223> AMIDATION <400> 273 Asp Xaa His Xaa Arg Trp Xaa 1 5 <210> 274 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (1)..(6) <223> cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = His, 1-amino-1-cyclopropanecarboxylic acid (A3c), 1-amino-1cyclopentanecarboxylic acid (A5c), 1-amino-1-cyclohexanecarboxylic acid (A6c), 2-aminoindan-2-carboxylic acid (Aic), or Apc <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (6)..(6) <223> AMIDATION <400> 274 Asp Xaa Xaa Arg Trp Lys 1 5 <210> 275 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(6) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = His, 1-amino-1-cyclopropanecarboxylic acid (A3c), 1-amino-1cyclopentanecarboxylic acid (A5c), 1-amino-1-cyclohexanecarboxylic acid (A6c), 2-aminoindan-2-carboxylic acid (Aic), or Apc <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (6)..(6) <223> AMIDATION <400> 275 Asp Xaa Xaa Arg Trp Lys 1 5 <210> 276 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (1)..(7) <223> cyclic <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (7)..(7) <223> Xaa = Lys, ornithine (Orn), 2,4-diaminobutyric acid (Dab), or 2,3-diaminopropionic acid (Dap) <220> <221> MOD_RES <222> (7)..(7) <223> AMIDATION <400> 276 Glu Xaa His Xaa Arg Trp Xaa 1 5 <210> 277 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(6) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (6)..(6) <223> AMIDATION <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = Lys or 2,3-diaminopropionic acid (Dap) <400> 277 Glu His Xaa Arg Trp Xaa 1 5 <210> 278 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Arg, norleucine (Nle), Gly, or D-Arg <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 278 Xaa Gly Cys Glu His Xaa Arg Trp Cys 1 5 <210> 279 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = norleucine (Nle), Gly, Ala, D-Ala, alpha-aminoisobutyric acid (Aib), Val, Ile, Leu, D-Arg, or Arg <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 279 Xaa Gly Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 280 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = norleucine (Nle) or Gly <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MISC_FEATURE <222> (9)..(9) <223> Xaa = penicillamine (Pen) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 280 Xaa Gly Cys Xaa His Xaa Arg Trp Xaa 1 5 <210> 281 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = norleucine (Nle) or Gly <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 281 Xaa Gly Cys Glu His Xaa Arg Trp Cys 1 5 <210> 282 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = D-Arg or Arg <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 282 Xaa Gly Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 283 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Ala, Val, or Gly <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = norleucine (Nle) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 283 Xaa Xaa Cys Glu His Xaa Arg Trp Cys 1 5 <210> 284 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = 1-amino-1-cyclohexanecarboxylic acid (A6c), Gly, Ala, D-Ala, Val, Leu, beta-cyclohexylalanine (Cha), or alpha-aminoisobutyric acid (Aib) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = norleucine (Nle) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 284 Xaa Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 285 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe or D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 285 Gly Arg Cys Glu His Xaa Arg Trp Cys 1 5 <210> 286 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe or D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 286 Gly Arg Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 287 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Arg <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 287 Gly Xaa Cys Glu His Xaa Arg Trp Cys 1 5 <210> 288 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (2)..(2) <223> Xaa = D-Arg <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe or D-beta-(2-naphythyl)alanine (D-2-Nal) <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 288 Gly Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 289 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = norleucine (Nle) <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 289 Xaa Ala Cys Glu His Xaa Arg Trp Cys 1 5 <210> 290 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = norleucine (Nle), Ala, D-Ala, alpha-aminoisobutyric acid (Aib), Val, alpha-aminobutyric acid (Abu), Leu, Ile, beta-cyclohexylalanine (Cha), 1-amino-1-cyclohexanecarboxylic acid (A6c), Phe, or Gly <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MISC_FEATURE <222> (3)..(3) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 290 Xaa Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 291 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (1)..(8) <223> cyclic <220> <221> MOD_RES <222> (1)..(1) <223> modified with hydantoin(CO) <220> <221> MISC_FEATURE <222> (5)..(5) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (8)..(8) <223> AMIDATION <400> 291 Gly Cys Glu His Xaa Arg Trp Cys 1 5 <210> 292 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> MISC_FEATURE <222> (1)..(1) <223> Xaa = Tyr, beta-(2-naphthyl)alanine (2-Nal), beta-(1-naphthyl)alanine (1-Nal), Phe, Trp, (S)-pentafluorophenylalanine (Pff), or His, all modified with acyl group (Ac) <220> <221> DOMAIN <222> (3)..(9) <223> cylic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 292 Xaa Arg Cys Xaa His Xaa Arg Trp Cys 1 5 <210> 293 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Melanocortin receptor ligand to treat insulin sensitivity <220> <221> DOMAIN <222> (3)..(9) <223> cyclic <220> <221> MISC_FEATURE <222> (4)..(4) <223> Xaa = D-Ala <220> <221> MISC_FEATURE <222> (6)..(6) <223> Xaa = D-Phe <220> <221> MOD_RES <222> (9)..(9) <223> AMIDATION <400> 293 His Arg Cys Xaa His Xaa Arg Trp Cys 1 5

Claims (35)

  1. 필요한 개체에서 인슐린 내성을 치료하기 위한 방법으로서, 유효량의 멜라노코르틴 수용체 4 작용제를 상기 개체에게 말초 투여하는 단계를 포함하는 인슐린 내성의 치료 방법.
  2. 제1항에 있어서, 인슐린 내성을 치료하기 위해 사용가능한 상기 멜라노코르틴 수용체 4 작용제는 하기 화합물 또는 그것의 약학적으로 허용가능한 염으로 이루어진 군으로부터 선택되는 것을 특징으로 하는 치료 방법:
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trpβ-Ala-Lys)-NH2; 서열번호 1
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; 서열번호 1
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; 서열번호 2
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2; 서열번호 3
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 3
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; 서열번호 3
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 2
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; 서열번호 4
    Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 5
    Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
    Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 6
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
    Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
    Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
    Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
    Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 7
    Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 8
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
    Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
    Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
    Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
    Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 9
    Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
    Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
    Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
    Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
    Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; 서열번호 10
    Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    n-부타노일-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 12
    Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; 서열번호 11
    Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
    Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
    Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
    Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
    Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; 서열번호 13
    Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; 서열번호 14
    Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; 서열번호 14
    Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; 서열번호 14
    Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; 서열번호 14
    Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; 서열번호 14
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; 서열번호 15
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 15
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; 서열번호 15
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; 서열번호 15
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; 서열번호 15
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 16
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; 서열번호 16
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; 서열번호 16
    n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 17
    n-부타노일-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 17
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; 서열번호 18
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; 서열번호 18
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; 서열번호 18
    Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 59
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2; 서열번호 19
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; 서열번호 20
    Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 21
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
    Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 22
    D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 23
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
    D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 25
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; 서열번호 24
    D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; 서열번호 26
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 27
    Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2; 서열번호 28
    Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; 서열번호 28
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; 서열번호 29
    Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 30
    Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 31
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
    Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 32
    Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 33
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
    Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 34
    Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 36
    Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; 서열번호 37
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; 서열번호 38
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; 서열번호 38
    Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; 서열번호 39
    Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2; 서열번호 39
    Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
    Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; 서열번호 40
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; 서열번호 41
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; 서열번호 42
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; 서열번호 43
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; 서열번호 43
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; 서열번호 43
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; 서열번호 42
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; 서열번호 41
    Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; 서열번호 44
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; 서열번호 45
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; 서열번호 45
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; 서열번호 45
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; 서열번호 45
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; 서열번호 46
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; 서열번호 46
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; 서열번호 46
    Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; 서열번호 46
    Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; 서열번호 47
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; 서열번호 48
    Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; 서열번호 49
    Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
    Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; 서열번호 50
    Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
    Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
    Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; 서열번호 52
    Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; 서열번호 51
    Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
    Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; 서열번호 53
    Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 35
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2; 서열번호 54
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2; 서열번호 54
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; 서열번호 54
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; 서열번호 54
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; 서열번호 54
    Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 55
    Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 55
    Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 56
    Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; 서열번호 56
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; 서열번호 57
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; 서열번호 57
    Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2; 서열번호 58
    Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 60)
    Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2; (서열번호 61)
    Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 62)
    Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 63)
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 64)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 65)
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 66)
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 67)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 68)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 69)
    Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 70)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 72)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 73)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 74)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 75)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2; (서열번호 76)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2; (서열번호 77)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2; (서열번호 78)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 79)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro) 2 -Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 80)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 82)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 81)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 84)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 83)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2; (서열번호 85)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2; (서열번호 86)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2; (서열번호 87)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 71)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 89)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 88)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 90)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 91)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 95)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 96)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 97)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 92)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 98)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 99)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 104)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 105)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 100)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 101)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 102)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 103)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 113)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 114)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 115)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 116)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 118)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 119)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 120)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 121)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 122)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2; (서열번호 124)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 125)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 126)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 127)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 128)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 130)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 133)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 134)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2; (서열번호 135)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2; (서열번호 137)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2; (서열번호 136)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 138)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 139)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 140)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 141)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 142)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2; (서열번호 143)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2; (서열번호 144)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 148)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149);
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 149)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 150)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 151)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 152)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 153)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 154)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 155)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 156)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 157)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 158)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 159)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 160)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 161)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 162)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 163)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 164)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 165)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 166)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 167)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 168)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 169)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 169)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 170)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 171)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 172)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 173)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 174)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 175)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 176)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 177)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 178)
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 179)
    D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 180)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 181)
    Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 182)
    Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
    Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 184)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 183)
    Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
    Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
    Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 185)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 186)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 187)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 188)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 189)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 190)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 191)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 192)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 193)
    Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 194)
    Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 195)
    Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 196)
    Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 197)
    Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 198)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 199)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 200)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 201)
    Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 202)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 203)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 204)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 205)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 206)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 207)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 208)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 210)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 209)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 211)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 212)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 213)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 267)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 214)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 216)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 215)
    D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 217)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 218)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 219)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 220)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 221)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 222)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 223)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 224)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 225)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 226)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 227)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 228)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 229)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 230)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 231)
    D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 232)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 233)
    Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 234)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 235)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 236)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 237)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 238)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 239)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 240)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 241)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 242)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 243)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 244)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 245)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 246)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 247)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 248)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 249)
    Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 250)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 251)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 252)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 253)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 254)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 255)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 256)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 257)
    Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 258)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 259)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 260)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 261)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 262)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (서열번호 263)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (서열번호 264)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (서열번호 265)
    Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (서열번호 266)
    Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2 ; (서열번호 268)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 269)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 210)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270)
    Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2; (서열번호 270)
    c[히단토인(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
    c[히단토인(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 271)
    c[히단토인(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
    c[히단토인(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2; (서열번호 272)
    c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 273)
    c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 273)
    c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 273)
    c[히단토인(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 273)
    c[히단토인(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인 (C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2; (서열번호 274)
    c[히단토인(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2; (서열번호 275)
    c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2; (서열번호 276)
    c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; (서열번호 276)
    c[히단토인(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 276)
    c[히단토인(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2; (서열번호 277)
    히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
    히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
    히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
    히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
    히단토인(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (서열번호 280)
    히단토인(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
    히단토인(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 281)
    히단토인(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 278)
    히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 279)
    히단토인(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
    히단토인(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 282)
    히단토인(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
    히단토인(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
    히단토인(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 283)
    히단토인(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 284)
    히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 285)
    히단토인(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 285)
    히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 286)
    히단토인(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 286)
    히단토인(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 287)
    히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 288)
    히단토인(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; (서열번호 288)
    히단토인(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 289)
    c[히단토인(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2, (서열번호 290)
    c[히단토인(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 290)
    c[히단토인(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2; (서열번호 291)
    Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
    Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
    Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2; (서열번호 292)
    Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
    Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
    Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292)
    H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 293)
    Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (서열번호 292).
  3. 제2항에 있어서, 상기 화합물이 Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 50) 또는 그것의 약학적으로 허용가능한 염인 것을 특징으로 하는 치료 방법.
  4. 제2항에 있어서, 상기 화합물이 히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 또는 그것의 약학적으로 허용가능한 염인 것을 특징으로 하는 치료 방법.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 개체는 비만 개체인 것을 특징으로 하는 치료 방법.
  6. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 개체는 과체중 개체인 것을 특징으로 하는 치료 방법.
  7. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 개체는 정상 체중 개체인 것을 특징으로 하는 치료 방법.
  8. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 개체는 저체중 개체인 것을 특징으로 하는 치료 방법.
  9. 제5항에 있어서, 상기 비만 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  10. 제6항에 있어서, 상기 과체중 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  11. 제7항에 있어서, 상기 정상 체중 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  12. 제8항에 있어서, 상기 저체중 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  13. 제1항에 있어서, 상기 말초 투여는 경구, 피하, 복막내, 근육내, 정맥내, 직장, 경피 또는 코내 투여인 것을 특징으로 하는 치료 방법.
  14. 제13항에 있어서, 상기 투여는 연속적으로, 매시간, 매일 4회, 매일 3회, 매일 2회, 매일 1회, 이틀에 1회, 매주 2회, 매주 1회, 2주에 1회, 매달 1회, 또는 2달에 1회 투여인 것을 특징으로 하는 치료 방법.
  15. 제14항에 있어서, 상기 투여는 연속 투여인 것을 특징으로 하는 치료 방법.
  16. 제14항에 있어서, 상기 투여는 매일 1회 투여인 것을 특징으로 하는 치료 방법.
  17. 제14항에 있어서, 상기 투여는 매주 1회 투여인 것을 특징으로 하는 치료 방법.
  18. 제14항에 있어서, 상기 투여는 2주에 1회 투여인 것을 특징으로 하는 치료 방법.
  19. 제14항에 있어서, 상기 투여는 매달 1회 투여인 것을 특징으로 하는 치료 방법.
  20. 제14항에 있어서, 상기 투여는 2달에 1회 투여인 것을 특징으로 하는 치료 방법.
  21. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 필요한 개체에서 인슐린 내성을 치료하기 위한 유효량의 멜라노코르틴 수용체 4 작용제의 말초 투여는 상기 개체의 체중도 감소시키는 것을 특징으로 하는 치료 방법.
  22. 제21항에 있어서, 상기 화합물이 Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 50) 또는 그것의 약학적으로 허용가능한 염인 것을 특징으로 하는 치료 방법.
  23. 제21항에 있어서, 상기 화합물이 히단토인(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (서열번호 278) 또는 그것의 약학적으로 허용가능한 염인 것을 특징으로 하는 치료 방법.
  24. 제21항 내지 제23항 중 어느 한 항에 있어서, 상기 개체는 비만 개체인 것을 특징으로 하는 치료 방법.
  25. 제21항 내지 제23항 중 어느 한 항에 있어서, 상기 개체는 과체중 개체인 것을 특징으로 하는 치료 방법.
  26. 제24항에 있어서, 상기 비만 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  27. 제25항에 있어서, 상기 과체중 개체는 II형 당뇨병을 앓고 있는 것을 특징으로 하는 치료 방법.
  28. 제21항에 있어서, 상기 말초 투여는 경구, 피하, 복막내, 근육내, 정맥내, 직장, 경피 또는 코내 투여인 것을 특징으로 하는 치료 방법.
  29. 제28항에 있어서, 상기 투여는 연속적으로, 매시간, 매일 4회, 매일 3회, 매일 2회, 매일 1회, 이틀에 1회, 매주 2회, 매주 1회, 2주에 1회, 매달 1회, 또는 2달에 1회 투여인 것을 특징으로 하는 치료 방법.
  30. 제29항에 있어서, 상기 투여는 연속 투여인 것을 특징으로 하는 치료 방법.
  31. 제29항에 있어서, 상기 투여는 매일 1회인 것을 특징으로 하는 치료 방법.
  32. 제29항에 있어서, 상기 투여는 매주 1회인 것을 특징으로 하는 치료 방법.
  33. 제29항에 있어서, 상기 투여는 2주에 1회인 것을 특징으로 하는 치료 방법.
  34. 제29항에 있어서, 상기 투여는 매달 1회인 것을 특징으로 하는 치료 방법.
  35. 제29항에 있어서, 상기 투여는 2달에 1회인 것을 특징으로 하는 치료 방법.
KR1020147036380A 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도 KR20150013339A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US193307P 2007-11-05 2007-11-05
US61/001,933 2007-11-05
PCT/US2008/012490 WO2009061411A2 (en) 2007-11-05 2008-11-05 Use melanocortins to treat insulin sensitivity

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
KR1020137011647A Division KR101662044B1 (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도

Publications (1)

Publication Number Publication Date
KR20150013339A true KR20150013339A (ko) 2015-02-04

Family

ID=40626385

Family Applications (3)

Application Number Title Priority Date Filing Date
KR1020147036380A KR20150013339A (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도
KR1020137011647A KR101662044B1 (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도
KR1020107012327A KR101290623B1 (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도

Family Applications After (2)

Application Number Title Priority Date Filing Date
KR1020137011647A KR101662044B1 (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도
KR1020107012327A KR101290623B1 (ko) 2007-11-05 2008-11-05 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도

Country Status (21)

Country Link
US (6) US9155777B2 (ko)
EP (2) EP2214693B1 (ko)
JP (3) JP2011502987A (ko)
KR (3) KR20150013339A (ko)
CN (2) CN101980717A (ko)
AR (1) AR069461A1 (ko)
AU (1) AU2008325194B2 (ko)
BR (1) BRPI0819188B1 (ko)
CA (2) CA2952095C (ko)
DK (1) DK2214693T3 (ko)
ES (2) ES2690556T3 (ko)
HK (3) HK1146242A1 (ko)
HU (1) HUE026842T2 (ko)
IL (2) IL205554A (ko)
NZ (1) NZ585131A (ko)
PL (1) PL2214693T3 (ko)
PT (2) PT2214693E (ko)
RU (1) RU2453328C2 (ko)
TR (1) TR201815292T4 (ko)
TW (1) TWI374030B (ko)
WO (1) WO2009061411A2 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11763106B2 (en) 2018-06-05 2023-09-19 The Research Foundation For The State University Of New York Method for passive wireless channel estimation in radio frequency network and apparatus for same

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8563000B2 (en) * 2007-05-25 2013-10-22 Ipsen Pharma S.A.S. Melanocortin receptor ligands modified with hydantoin
TR201815292T4 (tr) 2007-11-05 2018-11-21 Board Of Supervisors Of Louisiana State Univ And Agriculture And Mechanical College İnsüli̇n duyarliliğinin tedavi̇si̇nde melanokorti̇nleri̇n kullanimi.
JP5805632B2 (ja) 2009-06-08 2015-11-04 パラティン テクノロジーズ, インコーポレイテッドPalatin Technologies, Inc. メラノコルチン受容体に特異的なペプチド
WO2010144341A2 (en) 2009-06-08 2010-12-16 Palatin Technologies, Inc. Lactam-bridged melanocortin receptor-specific peptides
CA2769883A1 (en) * 2009-08-05 2011-02-10 Ipsen Pharma S.A.S. Use of melanocortins to treat dyslipidemia
CA2809803A1 (en) * 2009-08-31 2011-03-03 Tensive Controls, Inc. Stabilized melanocortin ligands
US9314509B2 (en) 2009-11-16 2016-04-19 Ipsen Pharma S.A.S. Pharmaceutical compositions of melanocortin receptor ligands
NZ599774A (en) 2009-11-23 2014-11-28 Palatin Technologies Inc Melanocortin-1 receptor-specific cyclic peptides
EA201290295A1 (ru) 2009-11-23 2013-01-30 Палатин Текнолоджиз, Инк. Специфичные к рецептору меланокортина-1 линейные пептиды
MX341642B (es) * 2011-06-14 2016-08-29 Ipsen Pharma Sas Composicion de liberacion sostenida que contiene peptidos como ingredientes activos.
PT2797615T (pt) * 2011-12-29 2019-07-11 Rhythm Pharmaceuticals Inc Método de tratamento de distúrbios associados ao recetor de melanocortina-4 em portadores heterozigóticos
WO2013138340A1 (en) 2012-03-13 2013-09-19 Tensive Controls Inc. Melanocortin analogs having enhanced activity and transport
KR102378943B1 (ko) 2013-03-15 2022-03-25 리듬 파마슈티컬즈, 인코포레이티드 약학적 조성물
EP3450449A3 (en) 2013-03-15 2019-06-12 Rhythm Pharmaceuticals, Inc. Peptide compositions
US10314883B2 (en) 2015-02-13 2019-06-11 University Of Virginia Patent Foundation Compositions and methods for regulating blood pressure
WO2017019952A1 (en) 2015-07-29 2017-02-02 University Of Virginia Patent Foundation Compositions and methods for regulating leukocyte adhesion
WO2017049140A2 (en) 2015-09-18 2017-03-23 Wake Forest University Health Sciences Angiotensin (1-7) analogs and methods relating thereto
US11124541B2 (en) * 2016-10-18 2021-09-21 Regents Of The University Of Minnesota Chimeric melanocortin ligands and methods of use thereof
US11332499B2 (en) 2018-08-16 2022-05-17 Regents Of The University Of Minnesota Cyclic peptides and methods of use thereof

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5672659A (en) 1993-01-06 1997-09-30 Kinerton Limited Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides
US5595760A (en) 1994-09-02 1997-01-21 Delab Sustained release of peptides from pharmaceutical compositions
US5665702A (en) 1995-06-06 1997-09-09 Biomeasure Incorporated Ionic molecular conjugates of N-acylated derivatives of poly(2-amino-2-deoxy-D-glucose) and polypeptides
US5916883A (en) 1996-11-01 1999-06-29 Poly-Med, Inc. Acylated cyclodextrin derivatives
EP1322954A4 (en) * 2000-09-13 2005-08-03 Eleanor Roosevelt Inst METHOD FOR TREATING INSULIN RESISTANCE IN OVERWEIGHT AND DIABETES
JP2005531583A (ja) * 2002-05-23 2005-10-20 カイロン コーポレイション 置換キナゾリノン化合物
ES2286345T3 (es) * 2003-03-20 2007-12-01 Santhera Pharmaceuticals (Schweiz) Ag Derivados de piperidina y piperazina substituidos como moduladores del receptor de melanocortina-4.
EP1610789B1 (en) 2003-03-26 2010-07-21 Merck Sharp & Dohme Corp. Bicyclic piperidine derivatives as melanocortin-4 receptor agonists
CA2523408A1 (en) 2003-05-09 2004-11-18 Novo Nordisk A\S Peptides for use in treating obesity
CN1784423A (zh) * 2003-05-09 2006-06-07 诺沃挪第克公司 用于治疗肥胖的肽
KR20060026011A (ko) * 2003-05-09 2006-03-22 노보 노르디스크 에이/에스 비만 치료용 펩티드
US20070105759A1 (en) * 2003-06-19 2007-05-10 Eli Lilly And Company Melanocortin receptor 4 (mc4) agonists and their uses
WO2005102377A1 (en) * 2004-03-29 2005-11-03 Eli Lilly And Company Uses of melanocortin-4 receptor (mc4r) agonist peptides administered by continuous infusion
EP1807102A2 (en) * 2004-10-29 2007-07-18 Merck & Co., Inc. Compositions and methods for the treatment of obesity and sexual dysfunction
KR20080041639A (ko) * 2005-07-08 2008-05-13 소시에떼 더 콘세이유 더 레세르세 에 다플리까띠옹 시엔띠피끄, 에스.아.에스. 멜라노코르틴 수용체의 리간드
HUE037147T2 (hu) * 2005-07-08 2018-08-28 Ipsen Pharma Melanokortin-receptor ligandumai
EP2135603B1 (en) 2005-11-22 2013-01-02 Orexigen Therapeutics, Inc. Compositions and methods for increasing insulin sensitivity
US8563000B2 (en) * 2007-05-25 2013-10-22 Ipsen Pharma S.A.S. Melanocortin receptor ligands modified with hydantoin
US20100173834A1 (en) 2007-06-15 2010-07-08 Zheng Xin Dong Cyclic peptide melanocortin receptor ligands
TR201815292T4 (tr) * 2007-11-05 2018-11-21 Board Of Supervisors Of Louisiana State Univ And Agriculture And Mechanical College İnsüli̇n duyarliliğinin tedavi̇si̇nde melanokorti̇nleri̇n kullanimi.
CA2769883A1 (en) 2009-08-05 2011-02-10 Ipsen Pharma S.A.S. Use of melanocortins to treat dyslipidemia

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11763106B2 (en) 2018-06-05 2023-09-19 The Research Foundation For The State University Of New York Method for passive wireless channel estimation in radio frequency network and apparatus for same

Also Published As

Publication number Publication date
PT2979703T (pt) 2018-10-31
KR20130065725A (ko) 2013-06-19
ES2690556T3 (es) 2018-11-21
US9155777B2 (en) 2015-10-13
US20220339239A1 (en) 2022-10-27
JP2013144690A (ja) 2013-07-25
NZ585131A (en) 2012-10-26
WO2009061411A3 (en) 2010-04-15
JP5964767B2 (ja) 2016-08-03
KR101662044B1 (ko) 2016-10-04
KR20100075680A (ko) 2010-07-02
CA2704651A1 (en) 2009-05-14
EP2214693B1 (en) 2015-09-09
IL205554A0 (en) 2010-12-30
JP2011502987A (ja) 2011-01-27
AR069461A1 (es) 2010-01-27
TR201815292T4 (tr) 2018-11-21
HK1221147A1 (zh) 2017-05-26
US9439943B2 (en) 2016-09-13
CN103316345A (zh) 2013-09-25
US20180303899A1 (en) 2018-10-25
KR101290623B1 (ko) 2013-08-07
CA2952095C (en) 2020-02-18
TW200932258A (en) 2009-08-01
BRPI0819188A2 (pt) 2015-09-01
CA2704651C (en) 2017-03-07
EP2979703B1 (en) 2018-07-18
IL205554A (en) 2017-01-31
PL2214693T3 (pl) 2016-03-31
PT2214693E (pt) 2015-12-07
US20150366934A1 (en) 2015-12-24
US20100311647A1 (en) 2010-12-09
US20160354429A1 (en) 2016-12-08
IL249998A0 (en) 2017-03-30
EP2979703A1 (en) 2016-02-03
EP2214693A4 (en) 2012-04-11
CA2952095A1 (en) 2009-05-14
ES2555522T3 (es) 2016-01-04
TWI374030B (en) 2012-10-11
HK1146242A1 (en) 2011-05-27
CN101980717A (zh) 2011-02-23
JP2015131827A (ja) 2015-07-23
AU2008325194A1 (en) 2009-05-14
CN103316345B (zh) 2016-05-18
EP2214693A2 (en) 2010-08-11
BRPI0819188B1 (pt) 2021-06-22
HK1184692A1 (zh) 2014-01-30
WO2009061411A2 (en) 2009-05-14
DK2214693T3 (en) 2015-11-30
RU2010122897A (ru) 2011-12-20
US9827286B2 (en) 2017-11-28
AU2008325194B2 (en) 2012-04-19
RU2453328C2 (ru) 2012-06-20
US20190111105A1 (en) 2019-04-18
HUE026842T2 (en) 2016-08-29
IL249998B (en) 2018-07-31

Similar Documents

Publication Publication Date Title
KR101662044B1 (ko) 인슐린 민감성을 치료하기 위한 멜라노코르틴의 용도
KR20080041639A (ko) 멜라노코르틴 수용체의 리간드
KR20080049711A (ko) 멜라노코르틴 수용체 리간드
US20130331324A1 (en) Use of melanocortins to treat dyslipidemia

Legal Events

Date Code Title Description
A107 Divisional application of patent
A201 Request for examination
E902 Notification of reason for refusal
E90F Notification of reason for final refusal
WITB Written withdrawal of application