Roles of Hyp Residues in the Folding and Activity of μ-Conotoxin GIIIA, a Peptide Blocker of Muscle Sodium Channels

Abstract

Attempts were made to synthesize seven analogs of µ-conotoxin GIIIA, a specific blocker of muscle sodium channels, by replacing the three Hyp residues (Hyp6, Hyp7, and Hyp17) with various amino acids. Replacement with Ala residue at these positions resulted in a very low isolation yield, suggesting that these three Hyp residues are essential for the folding of the molecule. CD spectra of the synthesized analogs suggest that, once synthesized, the replacement did not affect the three dimensional structure. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the hydroxyl group at side chains of Hyp residues are not essential for the activity.