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

OBJECTIVES:To design and synthesize peptide inhibitors based on transient receptor potential vanilloid 1 (TRPV1) ion channel agonist red head toxin (RhTx), and to validate their function. METHODS:Based on previous studies on the relation of molecular structure and function of 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, 4 of them 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 rationally design the N terminal residues in RhTx.