Chiral Recognition of Flexible Melatonin Receptor Ligands Induced by Conformational Equilibria.

ABSTRACT: N-anilinoethylamides are a class of melatoninergic agents with the aniline portion mimicking the indole ring of the natural ligand and the ethylamide chain reproducing that of melatonin. The simplest compound in this class, N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (UCM793), has nanomolar binding affinity for MT₁ and MT₂ membrane receptors. To explore the effect of chain conformation on receptor binding, a methyl group was inserted on the methylene alpha or beta to the amide nitrogen and conformational equilibria were investigated by NMR spectroscopy and molecular dynamics simulations. Receptor affinity was conserved only for the beta-methyl derivative, which also showed significant stereoselectivity, with the (S) enantiomer being the eut

SUBMITTER: Elisi GM 

PROVIDER: S-EPMC7570888 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature