药学学报, 2021, 56(9): 2567-2572
引用本文:
任茅茅, 张宝建, 孙鑫, 杨芳, 长孙东亭, 董帅*, 罗素兰*. 赖氨酸辅助三聚氯氰连接子环化α-芋螺毒素[A10L]PnIA[J]. 药学学报, 2021, 56(9): 2567-2572.
REN Mao-mao, ZHANG Bao-jian, SUN Xin, YANG Fang, ZHANGSUN Dong-ting, DONG Shuai*, LUO Su-lan*. Cyclization of α-conotoxin[A10L]PnIA with lysine assisted cyanuric chloride linker[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2567-2572.

赖氨酸辅助三聚氯氰连接子环化α-芋螺毒素[A10L]PnIA
任茅茅, 张宝建, 孙鑫, 杨芳, 长孙东亭, 董帅*, 罗素兰*
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
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。
关键词:    α-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     
Cyclization of α-conotoxin[A10L]PnIA with lysine assisted cyanuric chloride linker
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
Abstract:
The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-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 against α7 and α3β2 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 various α-conotoxins.
Key words:    α-conotoxin[A10L] PnIA    peptide cyclization    cyanuric chloride linker    nAChRs   
收稿日期: 2021-05-18
DOI: 10.16438/j.0513-4870.2021-0750
基金项目: 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).
通讯作者: 董帅,Tel:86-898-66289538;E-mail:dongshuai_1024@163.com;罗素兰,E-mail:luosulan2003@163.com
Email: dongshuai_1024@163.com;luosulan2003@163.com
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