PeIA-5466: A Novel Peptide Antagonist Containing Non-natural Amino Acids That Selectively Targets α3β2 Nicotinic Acetylcholine Receptors.

ABSTRACT: Pharmacologically distinguishing α3β2 nicotinic acetylcholine receptors (nAChRs) from closely related subtypes, particularly α6β2, has been challenging due to the lack of subtype-selective ligands. We created analogs of α-conotoxin (α-Ctx) PeIA to identify ligand-receptor interactions that could be exploited to selectively increase potency and selectivity for α3β2 nAChRs. A series of PeIA analogs were synthesized by replacing amino acid residues in the second disulfide loop with standard or nonstandard residues and assessing their activity on α3β2 and α6/α3β2β3 nAChRs heterologously expressed in Xenopus laevis oocytes. Asparagine¹¹ was found to occupy a pivotal position, and when replaced with negatively charged amino acids, selectivity for α3β2 over α6/α3β2β3 nAChRs was

SUBMITTER: Hone AJ 

PROVIDER: S-EPMC7342494 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature