Cyclization of α-conotoxin A10LPnIA with lysine assisted cyanuric chloride linker

VernacularTitle:赖氨酸辅助三聚氯氰连接子环化α-芋螺毒素[A10L]PnIA
Author: Mao-mao REN ; Bao-jian ZHANG ; Xin SUN ; Fang YANG ; Dong-ting ZHANGSUN ; Shuai DONG ; Su-lan LUO
Publication Type:Research Article
Keywords: italic>α-conotoxin [A10L] PnIA; peptide cyclization; cyanuric chloride linker; nAChRs
From: Acta Pharmaceutica Sinica 2021;56(9):2567-2572
CountryChina
Language:Chinese
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.