title: Exploring organosilane amines as potent inhibitors and structural probes of influenza a virus M2 proton channel.
abstract: We describe the use of organosilanes as inhibitors and structural probes of a membrane protein, the M2 proton channel from influenza A virus. Organosilane amine inhibitors were found to be generally as potent as their carbon analogues in targeting WT A/M2 and more potent against the drug-resistant A/M2-V27A mutant. In addition, intermolecular NOESY spectra with dimethyl-substituted organosilane amine inhibitors clearly located the drug binding site at the N-terminal lumen of the A/M2 channel close to V27.
authors.affiliation: Department of Chemistry, School of Medicine, University of Pennsylvania, Philadelphia, 19104-6059, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Chunlong
authors.initials: C
authors.lastname: Ma
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Pinto
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D024882:Drug Resistance, Viral; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy; D008958:Models, Molecular; D009154:Mutation; D054328:Proton Pump Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017494:Proton Pumps / Q000235:genetics / Q000378:metabolism*; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000588:Amines; D000998:Antiviral Agents; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D012821:Silanes; D014764:Viral Proteins