Raising the Bar On-Bead: Efficient On-Resin Synthesis of α-Conotoxin LvIA.

ABSTRACT: α4/7-Conotoxin LvIA is an isoform-selective inhibitor of the α3β2 nicotinic acetylcholine receptor. An efficient strategy for the synthesis of this toxin is critical to advancing its utility as a probe for receptor function and as a potential pharmaceutical lead target. On-resin methods for peptide synthesis offer potential synthetic advantages; however, strategies for on-resin formation of multiple disulfides have historically been low-yielding. Here, we harness the reactivity of the Allocam protecting group and employ 3-amino acid spacer strategy to synthesize α4/7-conotoxin LvIA via three different on-resin strategies, each of which results in an isolated yield higher than prior fully on-resin approaches.

SUBMITTER: Kondasinghe TD 

PROVIDER: S-EPMC6764457 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature