Synthesis and biological activity study of the retro-isomer of RhTx against TRPV1

Abstract

TRPV1 is a ligand-gated ion channel and plays an important role in detecting noxious heat and pain. A new TRPV1 antagonist RL-RhTx was discovered.

DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

“…The trends of CD spectra of different folded peptides were basically identical, which was consistent with previous studies (Figure 4B). 34 The CD spectrum of linear peptide 1 was significantly different from those of folded RhTx, which indicates that disulfide bonds were necessary for maintaining the structure of RhTx.…”

“…Using CHO cells overexpressing TRPV1, the agonistic effects of The time courses of TRPV1 currents showed that the folded peptides could induce the similar trend of the TRPV1 currents, which were comparable with the previous studies (Figure 5A-I). 34 Besides, linear peptide 1 could not activate TRPV1 channel, indicating the necessity of disulfide bonds (Figure 5J). There was no significant difference between the normalized currents induced by the folded peptides (Figure 5K).…”

“…The novel centipede toxin RhTx that is recently isolated from the venom of the Chinese red‐headed centipede contains 27 amino acid residues and two pairs of disulfide bonds (Figure 1). 33–35 …”

“…[30][31][32] The novel centipede toxin RhTx that is recently isolated from the venom of the Chinese red-headed centipede contains 27 amino acid residues and two pairs of disulfide bonds (Figure 1). [33][34][35] RhTx could rapidly target and activate the extracellular domain of TRPV1 with high specificity and affinity, inducing conformational rearrangement and causing severe pain. These properties make RhTx an especial tool for further mechanism studies of TRPV1.…”