Interaction between an amantadine analogue and the transmembrane portion of the influenza A M2 protein in liposomes probed by 1H NMR spectroscopy of the ligand

Antonios Kolocouris; Raino K Hansen; R William Broadhurst

doi:10.1021/jm0496685

Interaction between an amantadine analogue and the transmembrane portion of the influenza A M2 protein in liposomes probed by 1H NMR spectroscopy of the ligand

J Med Chem. 2004 Sep 23;47(20):4975-8. doi: 10.1021/jm0496685.

Authors

Antonios Kolocouris¹, Raino K Hansen, R William Broadhurst

Affiliation

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, Athens 15 771, Greece.

PMID: 15369403
DOI: 10.1021/jm0496685

Abstract

1H NMR spectroscopy of a fluoroamantadine ligand was used to probe the pH dependence of binding to the transmembrane peptide fragment of the influenza A M2 proton channel (M2TM) incorporated into 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes. Above pH 7.5, when M2TM bound the ligand, fluoroamantadine resonances became too broad to be detected. Fluoroamantadine interacted weakly with the liposomes, indicating it may first bind to the bilayer and then block target channels after diffusion across the membrane surface.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amantadine / analogs & derivatives*
Amantadine / metabolism*
Amino Acid Sequence
Antiviral Agents / chemistry
Antiviral Agents / metabolism*
Cell Membrane / metabolism
Dimyristoylphosphatidylcholine / chemistry
Hydrogen-Ion Concentration
Ligands
Liposomes / chemistry*
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Protein Structure, Tertiary
Viral Matrix Proteins / chemistry
Viral Matrix Proteins / metabolism*

Substances

Antiviral Agents
Ligands
Liposomes
M-protein, influenza virus
M2 protein, Influenza A virus
Viral Matrix Proteins
Amantadine
Dimyristoylphosphatidylcholine