Design,synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx
10.3724/zdxbyxb-2023-0465
- VernacularTitle:靶向瞬时受体电位香草酸亚型1离子通道的Nplus-RhTx多肽抑制剂理性设计及功能验证
- Author:
Heng ZHANG
1
;
Jiawei WANG
;
Fan YANG
Author Information
1. 浙江大学医学院基础医学院生物物理系,浙江 杭州 310058
- Keywords:
Transient receptor potential vanilloid 1;
Ion channels;
Peptides;
Rational design;
Electrophysiology
- From:
Journal of Zhejiang University. Medical sciences
2024;53(2):201-206
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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 IC50 of(188.3±4.7),(193.6±18.0),(282.8±11.9)and(299.5±6.4)μmol/L,respectively.Conclusion:It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.
