KR102497726B1 - 인슐린 저항성에 대한 개선된 펩티드 제약 - Google Patents
인슐린 저항성에 대한 개선된 펩티드 제약 Download PDFInfo
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Abstract
Description
추가로, 도 1의 표 1은 도 1의 표 1에 제시된 바와 같이, 각각 서열 번호 4-129를 가지는 화합물 EU-A300 내지 EU-A425에 대한 서열 번호를 제공한다. 도 1의 표 1의 화합물, 및 도 1의 표 1에 제시된 그의 각각의 서열 번호는 본원에서 출원된 명세서에 포함된다.
도 2. 도 2의 표 2는 본원에 기술된 방법에 의해 제조된 화합물을 도시한 것이다. 본 명세서는 서열 번호 1-3 및 서열 번호 318-343에 대한 서열을 제공한다. 추가로, 도 2의 표 2는 도 2의 표 2에 제시된 바와 같이, 각각 서열 번호 130-317을 가지는 화합물 EU-A426 내지 EU-599에 대한 서열 번호를 제공한다. 도 2의 표 2의 화합물, 및 도 2의 표 2에 제시된 그의 각각의 서열 번호는 본원에서 출원된 명세서에 포함된다.
도 3. 도 3은 GLP-1 수용체의 세포외 도메인의 결합 부위에 대한 x선 결정 구조(문헌 [Runge, S., et al. (2008) J Biol Chem 283: 11340-7])를 도시한 것이고, 본 발명의 펩티드 상의 계면활성제의 소수성 1'-알킬 부분에 의해 모사 및 치환되는 리간드 엑센딘-4(Val19*, Phe22*, Trp25*, Leu26*) 및 수용체의 임계 소수성 결합 요소를 도시한 것이다.
Claims (57)
- 링커 아미노산 U 및 서열 번호 1의 아미노산 잔기 aa1-aa20을 포함하는 펩티드에 공유 결합되어 있는, 계면활성제 X를 포함하는 펩티드 생성물:
<화학식(I-A)>
상기 식에서,
계면활성제 X는 하기 1-알킬 글리코시드이고:
상기 식에서,
A는 치환된 또는 비치환된 C8-C20 알킬기인 소수성기이고;,
B는 링커 아미노산 U(Lys)을 통해 펩티드에 공유 결합되는 친수성 글루쿠론산이고;
aa1은 His이고;
aa2는 Aib이고;
aa3은 Gln이고;
aa4는 Gly이고;
aa5는 Thr이고;
aa6은 Phe이고;
aa7은 Thr이고;
aa8은 Ser이고;
aa9는 Asp이고;
aa10은 Tyr이고;
aa11은 Ser이고;
aa12는 Lys이고;
aa13은 Tyr이고;
aa14는 Leu이고;
aa15는 Asp이고;
aa16은 Glu이고;
aa17은 U(Lys)이고;
aa18은 Ala이고;
aa19는 Ala이고;
aa20은 Lys이고;
aa17(Lys)은 계면활성제 X에의 공유 결합에 사용되고;
aa16과 aa20은 그의 측쇄를 통해 환화됨으로써 락탐 결합을 형성한다. - 삭제
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- 제1항에 있어서, 1-알킬 글리코시드가 O 연결된, S 연결된, N 연결된 또는 C 연결된 알킬 글리코시드인 것인 펩티드 생성물.
- 제1항에 있어서, 계면활성제 X가 1-에이코실 베타-D-글루쿠론산, 1-옥타데실 베타-D-글루쿠론산, 1-헥사데실 베타-D-글루쿠론산, 1-테트라데실 베타-D-글루쿠론산, 1-도데실 베타 D-글루쿠론산, 1-데실 베타-D-글루쿠론산, 1-옥틸 베타-D-글루쿠론산, 1-에이코실 베타-D-디글루쿠론산, 1-옥타데실 베타-D-디글루쿠론산, 1-헥사데실 베타-D-디글루쿠론산, 1-테트라데실 베타-D-디글루쿠론산, 1-도데실 베타-D-디글루쿠론산, 1-데실 베타-D-디글루쿠론산, 또는 1-옥틸 베타-D-디글루쿠론산을 포함하는 것인 펩티드 생성물.
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- 치료적 유효량의, 제1항에 따른 펩티드 생성물, 또는 이의 허용되는 염, 및 1 이상의 약학적으로 허용되는 담체 또는 부형제를 포함하는, 인슐린 저항성, 당뇨병, 심혈관 질환, 대사 증후군 또는 비만을 치료하는데 사용하기 위한 약학 조성물.
- 제14항에 있어서, 펩티드가 체중 감소를 초래하는 것인 약학 조성물.
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