赖氨酸辅助三聚氯氰连接子环化α-芋螺毒素[A10L]PnIA  

Cyclization ofα-conotoxin[A10L]PnIA with lysine assisted cyanuric chloride linker

作　　者：任茅茅 张宝建 孙鑫 杨芳 长孙东亭[1] 董帅 罗素兰[1] REN Mao-mao;ZHANG Bao-jian;SUN Xin;YANG Fang;ZHANGSUN Dong-ting;DONG Shuai;LUO Su-lan(Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou 570228,China)

机构地区：[1]海南大学热带生物资源教育部重点实验室,药学院,海南海口570228

出　　处：《药学学报》2021年第9期2567-2572,共6页Acta Pharmaceutica Sinica

基　　金：海南省自然科学基金项目(219QN150);海南大学教育教学改革研究项目(hdjy2045)。

摘　　要：三聚氯氰类连接子可用于环化多肽分子,但其并未应用于富含二硫键且氨基酸残基更多的α-芋螺毒素中。本研究通过赖氨酸辅助三聚氯氰连接子以28.92%~52.00%的产率高效合成环肽c[A10L]PnIA-1~4;活性评价结果表明c[A10L]PnIA-1对α7和α3β2烟碱型乙酰胆碱受体的IC50值相比于本体肽分别有5倍与7倍的升高,其亚型选择性得到保持;圆二色谱结果表明,环化后多肽二级结构无显著变化。该方法与芋螺毒素常用的首尾环化方法相比,具有反应快且产率高的优点,有望进一步应用于多种α-芋螺毒素的环化研究。The cyanuric chloride linkers have been used for cyclizing polypeptide,but not used forα-conotoxin,the peptides with rich disulfide bonds and more amino acid residues.In this study,cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00%yields.The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 againstα7 andα3β2 nAChR subtypes were 5 and 7 times higher than[A10L]PnIA respectively,and the subtype selectivity was maintained.The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure.Compared with the commonly used head-to-tail cyclization in conotoxin cyclization,this method has the advantages of rapid reaction and high yield,which is expected to be further applied to the cyclization study of variousα-conotoxins.

关 键 词：芋螺毒素[A10L]PnIA 多肽环化 三聚氯氰连接子 烟碱型乙酰胆碱受体 

分 类 号：R9I6[医药卫生—药学]