Distinct disulfide isomers of μ-conotoxins KIIIA and KIIIB block voltage-gated sodium channels.

ABSTRACT: In the preparation of synthetic conotoxins containing multiple disulfide bonds, oxidative folding can produce numerous permutations of disulfide bond connectivities. Establishing the native disulfide connectivities thus presents a significant challenge when the venom-derived peptide is not available, as is increasingly the case when conotoxins are identified from cDNA sequences. Here, we investigate the disulfide connectivity of μ-conotoxin KIIIA, which was predicted originally to have a [C1-C9,C2-C15,C4-C16] disulfide pattern based on homology with closely related μ-conotoxins. The two major isomers of synthetic μ-KIIIA formed during oxidative folding were purified and their disulfide connectivities mapped by direct mass spectrometric collision-induced dissociation fragmentation of the di

SUBMITTER: Khoo KK 

PROVIDER: S-EPMC4131687 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature