Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx. / é¶å‘çž¬æ—¶å—ä½“ç”µä½é¦™è‰é ¸äºšåž‹1离子通道的Nplus-RhTx多肽抑制剂理性设计及功能验证.

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.