Synthesis of full-length homodimer αD-VxXXB that targets human α7 nicotinic acetylcholine receptors.

ABSTRACT: αD-Conotoxin VxXXB is a pseudo-homodimer that allosterically inhibits nicotinic acetylcholine receptors (nAChRs) with high potency and selectivity. However, challenges in synthesizing αD-conotoxins have hindered further structure-function studies on this novel class of peptides. To address this gap, we synthesized and characterized its C-terminal domain (CTD) and N-terminal domain (NTD). The CTD inhibited α7 nAChRs (IC₅₀ of 23 nM, measured via FLIPR assays) and bound at the acetylcholine binding protein (Ls-AChBP) through an allosteric binding mode determined from radioligand binding assays. The anti-parallel dimeric NTD synthesised via a regioselective strategy also inhibited α7 nAChRs but with reduced potency (IC₅₀ of 30 μM). The α-ketoacid-hydr

SUBMITTER: Ho TNT 

PROVIDER: S-EPMC9667780 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature