基于 TRPV1 离子通道激动剂 RhTx 的肽抑制剂的设计、合成与功能验证。
Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.
机构信息
Department of Biophysics, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
出版信息
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Apr 25;53(2):201-207. doi: 10.3724/zdxbyxb-2023-0465.
OBJECTIVES
To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function.
METHODS
Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells.
RESULTS
Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively.
CONCLUSIONS
It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.
目的
设计并合成靶向瞬时受体电位香草酸 1 型（TRPV1）离子通道的肽类抑制剂，并验证其功能。
方法
基于先前对红头毒素（RhTx）的分子结构与功能关系的研究，我们设计并合理合成了一系列带正电荷氨基酸的肽类物质，这些正电荷氨基酸连接到 RhTx 的 N 端。通过活细胞内的膜片钳记录来验证这些 N 端加 RhTx 的肽类物质的功能。
结果
在所合成的 8 种 N 端加 RhTx 的肽类物质中，有 4 种肽类物质能够抑制由辣椒素激活的 TRPV1 离子通道，其半数抑制浓度（IC）分别为（188.3±4.7）、（193.6±18.0）、（282.8±11.9）和（299.5±6.4）µmol/L。
结论
基于 RhTx N 端残基的合理设计，开发 TRPV1 肽类抑制剂是可行的。
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