Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.

Q2 Medicine

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences Pub Date : 2024-04-25 DOI:10.3724/zdxbyxb-2023-0465

Heng Zhang, Jiawei Wang, Fan Yang

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引用次数: 0

Abstract

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 IC₅₀ 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.

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基于 TRPV1 离子通道激动剂 RhTx 的多肽抑制剂的设计、合成和功能验证。

研究目的方法：基于瞬时受体电位香草素1（TRPV1）离子通道激动剂红头毒素（RhTx），设计合成多肽抑制剂，并验证其功能：方法：根据以往对 RhTx 分子结构与功能关系的研究，合理设计并合成了一系列肽，这些肽的 N 端连接了带正电荷的氨基酸。这些 Nplus-RhTx 肽通过活细胞膜片钳记录进行了功能验证：结果：在合成的 8 种 Nplus-RhTx 肽中，有 4 种能抑制辣椒素激活的 TRPV1 离子通道，其 IC50 分别为（188.3±4.7）、（193.6±18.0）、（282.8±11.9）和（299.5±6.4）µmol/L：通过合理设计 RhTx 的 N 端残基，开发 TRPV1 肽抑制剂是可行的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences Medicine-Medicine (all)

CiteScore

3.80

自引率

0.00%

发文量