Cysteine [2,4] Disulfide Bond as a New Modifiable Site of α-Conotoxin TxIB.

ABSTRACT: α-Conotoxin TxIB, a selective antagonist of α6/α3β2β3 nicotinic acetylcholine receptor, could be a potential therapeutic agent for addiction and Parkinson's disease. As a peptide with a complex pharmacophoric conformation, it is important and difficult to find a modifiable site which can be modified effectively and efficiently without activity loss. In this study, three xylene scaffolds were individually reacted with one pair of the cysteine residues ([1,3] or [2,4]), and iodine oxidation was used to form a disulfide bond between the other pair. Overall, six analogs were synthesized with moderate isolated yields from 55% to 65%, which is four times higher than the traditional two-step oxidation with orthogonal protection on cysteines. The cysteine [2,4] modified analogs, with higher stabil

SUBMITTER: Zhang B 

PROVIDER: S-EPMC7926623 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature