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GLUCAGON-LIKE PEPTIDE-1 ANALOGUE MONOMER AND DIMER, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

机译:葡聚糖样肽-1类似物单体和二聚体,其制备方法及其应用

摘要

Provided are a glucagon-like peptide-1 (GLP-1) analogue monomer and dimmer, a preparation method therefor, and an application thereof. The GLP-1 analogue monomer comprises therein one cysteine; and the dimer is formed by two monomer molecules connected via an intermolecular disulfide bond formed by the cysteine. The cysteine-comprising GLP-1 monomer has the following general formula: 7HAEX10TFTSX15VSSYLEX22X23AAKEFIX30WLX33KGRG37, where X10 is a glycine or a cysteine, X15 is an aspartate or a cysteine, X22 is a glycine or a cysteine, X23 is a glutamyl thalidomide or a cysteine, X30 is an alanine or a cysteine, and X33 is a valine or a cysteine; and only one among X10, X15, X22, X23, X30, and X33 is cysteine. The GLP-1 analogue dimer of the present invention has an in vivo half-life of more than eight to 96 hours, thus facilitating clinical promotion and application.
机译:提供了一种胰高血糖素样肽-1(GLP-1)类似物单体和二聚体,其制备方法及其应用。 GLP-1类似物单体在其中包含一个半胱氨酸;所述二聚体由通过半胱氨酸形成的分子间二硫键连接的两个单体分子形成。包含半胱氨酸的GLP-1单体具有以下通式: 7 HAEX 10 TFTSX 15 VSSYLEX 22 X 23 AAKEFIX 30 WLX 33 KGRG 37 ,其中X 10 是甘氨酸或半胱氨酸,X 15 是天冬氨酸或半胱氨酸,X 22 是甘氨酸或半胱氨酸,X 23 是谷氨酰沙利度胺或半胱氨酸,X 30 是丙氨酸或半胱氨酸,X 33 是缬氨酸或半胱氨酸; X 10 ,X 15 ,X 22 ,X 23 ,X 30 < / Sub>,而X 33 是半胱氨酸。本发明的GLP-1类似物二聚体的体内半衰期超过8至96小时,因此有利于临床推广和应用。

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