胰岛素的脂肪链定位修饰及产物的表征

• 作 者: 何明磊 赵轶男 权春善 张伟 孙天竹
• 机 构: 大连民族学院生命科学学院,
• 出 处: 药物生物技术
• 发表日期: 2009年05期
• 关键词: 人胰岛素 脂肪链 定位 修饰

介绍了一种胰岛素修饰方法。该方法是在人胰岛素B链的C末端残基的α-羧基上共价连接一条脂肪链。其做法是以人胰岛素为起始原料,使用羧肽酶A在适当的溶液中将上述胰岛素B链C末端第一个氨基酸残基切掉,然后在有机相中以胰蛋白酶为催化剂,将一个连有脂肪链的氨基酸衍生物通过酶促反应连接到上述的去掉C末端第一个氨基酸的胰岛素上(此时C末端为赖氨酸)使之成为B链C末端上连接了脂肪链的新型胰岛素衍生物。该衍生物具有潜在的口服功能及长效功能。

An insulin modification method is introduced. This method involves the covalent attachment of a fatty chain to the alpha-carboxy group of the C-terminal residue of the human insulin B chain. Its approach is to use human insulin as a starting material, carboxypeptidase A in the appropriate solution will be the first of the C-terminal insulin B chain amino acid residues cut off, and then trypsin in the organic phase as a catalyst, a An amino acid derivative with an attached fatty chain is enzymatically linked to the above-described insulin with the C-terminal first amino acid (in this case C-terminal lysine) to be a new type of fatty chain with a C-terminal aliphatic chain Insulin derivatives. The derivatives have potential oral and long-acting functions.