title: Probing the cation binding modes of macrocyclic HCV protease inhibitor BILN 2061 by multinuclear NMR.
abstract: The ability of the macrocyclic HCV protease inhibitor BILN 2061 to bind different classes of cations has been studied by (15)N, (13)C, and (1)H NMR. (15)N NMR experiments were performed at natural abundance or with isotopically labeled materials. Three classes of cations: alkali metals, alkaline earth metals, and transition metals, were examined, using two members of each class. The behavior of each cation class was found to be different, and provided insight into how metal ions interact with the molecular scaffold. These specific interactions were uncovered by examining coordination shifts, NOE correlations, and line broadening across all three nuclei.
authors: Chemical Development and Analytical Development, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., Ridgefield, CT 06877, USA. carl.busacca@boehringer-ingelheim.com
authors: Carl A
authors: CA
authors: Busacca
authors: Paul-James
authors: PJ
authors: Jones
authors: Scot J
authors: SJ
authors: Campbell
authors: Anjan K
authors: AK
authors: Saha
authors: Nina C
authors: NC
authors: Gonnella
authors: Chris H
authors: CH
authors: Senanayake
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008672:Metals, Alkali / Q000737:chemistry*; D008673:Metals, Alkaline Earth / Q000737:chemistry*; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology; D028561:Transition Elements / Q000737:chemistry*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D002412:Cations; D047028:Macrocyclic Compounds; D008672:Metals, Alkali; D008673:Metals, Alkaline Earth; D011480:Protease Inhibitors; D011804:Quinolines; D013844:Thiazoles; D028561:Transition Elements; D017361:Viral Nonstructural Proteins; C479555:BILN 2061; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases