Referenced in: none

Automatically associated channels: Kir2.3

Title: Differential Binding of Rimantadine Enantiomers to Influenza A M2 Proton Channel.

Authors: Anna K Wright, Paratchata Batsomboon, Jian Dai, Ivan Hung, Huan-Xiang Zhou, Gregory B Dudley, Timothy A Cross

Journal, date & volume: J. Am. Chem. Soc., 2016 Feb 10 , 138, 1506-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26804976

Abstract
Rimantadine hydrochloride (α-methyl-1-adamantane-methalamine hydrochloride) is a chiral compound which exerts antiviral activity against the influenza A virus by inhibiting proton conductance of the M2 ion channel. In complex with M2, rimantadine has always been characterized as a racemic mixture. Here, we report the novel enantioselective synthesis of deuterium-labeled (R)- and (S)-rimantadine and the characterization of their protein-ligand interactions using solid-state NMR. Isotropic chemical shift changes strongly support differential binding of the enantiomers to the proton channel. Position restrained simulations satisfying distance restraints from (13)C-(2)H rotational-echo double-resonance NMR show marked differences in the hydrogen-bonding pattern of the two enantiomers at the binding site. Together these results suggest a complex set of interactions between (R)-rimantadine and the M2 proton channel, leading to a higher stability for this enantiomer of the drug in the channel pore.