ABSTRACT
Synthesis and stereochemical characterization of enantiomerically pure CPSMeG derivatives by NMR methods are reported. The effect of 5'-dimethoxytrityl on the conformational properties is described. It was found that in P-diastereomers the conformational differences about the C3'-O3' bond, as discernible from the delta J values, are enhanced by the presence of this protecting group.
Subject(s)
Cytosine/chemical synthesis , Dinucleoside Phosphates/chemical synthesis , Guanine/chemical synthesis , Magnetic Resonance Spectroscopy , Chromatography, Gel , Chromatography, Thin Layer , Cytosine/analogs & derivatives , Guanine/analogs & derivatives , Organophosphonates/chemistry , StereoisomerismABSTRACT
The binding of influenza A virus hemagglutinin to its cell surface receptor, alpha-linked 5-N-acetylneuraminic acid (sialic acid), was studied in solution. The effect of structural modifications introduced into the N-acetyl group of the sialic acid on the binding was monitored by determining the dissociation constants by proton nuclear magnetic resonance (1H NMR) spectroscopy. Methyl alpha-glycoside of N-thioacetylneuraminic acid showed high, whereas the corresponding N-methylcarbamoylneuraminic acid exhibited relatively low binding affinity towards the hemagglutinin.
Subject(s)
Glycosides/pharmacology , Influenza A virus/drug effects , Neuraminic Acids/pharmacology , Electrophoresis, Polyacrylamide Gel , Hemagglutinin Glycoproteins, Influenza Virus , Hemagglutinins, Viral/metabolism , Magnetic Resonance Spectroscopy , N-Acetylneuraminic Acid , Neuraminic Acids/chemistry , Sialic Acids/metabolism , SolutionsABSTRACT
The solution conformation of the disaccharide of avermectin B1a was examined by combining NMR data with theoretical conformational energy calculations. Carbon and proton resonances were assigned unambiguously using high-field, high-resolution 2D NMR correlation spectroscopy. 3JHH coupling constants were determined at 600 MHz. The minimum-energy conformation was attained through an extended hard-sphere exo-anomeric effect (HSEA) approach. The HSEA conformation was refined by considering the experimental nuclear Overhauser enhancement contacts. The resulting three-dimensional structure was confirmed by comparing its glycosidic dihedral angles to those calculated from experimental 3JCOCH coupling constants. Differences has been found in the glycosidic dihedral angles between the solution conformation and the X-ray structure.
