Primary and secondary structure of conotoxin GI, a neurotoxic tridecapeptide from a marine snail

Abstract

To determine the mode of disulphide bond formation in conotoxin GI, a tridecapeptide amide with 4 Cys residues, all 3 of its peptides having different modes of disulphide-bond formation were synthesized by solution procedure using selectively removable protective groups at the Cys residues. After deprotection with HF, one pair of acetamidomethyl groups was left unremoved, and then two sets of disulphide bonds were formed selectively. The toxic potency in mice of one product was comparable with that reported for native conotoxin GI and was almost 10-fold as high as that of the other two products. The toxicity of the native toxin reportedly is not regenerated upon reduction and reoxidation, but this study showed that the most toxic product was the most readily formed one.