RESUMEN
Quinolinate phosphoribosyltransferase was examined for susceptibility to different chemical modification reagents. Loss of enzyme activity with trinitrobenzenesulfonate (TNBS) occurred when 1.1 lysines per subunit were modified. Tryptic digestion of the modified enzyme followed by HPLC-MS analysis of the peptides showed Lys70 reacts with TNBS. Based on x-ray studies, this amino acid participates in a conformational change distant from the active site.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Escherichia coli/enzimología , Lisina/química , Pentosiltransferasa/antagonistas & inhibidores , Pentosiltransferasa/metabolismo , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Secuencia Conservada , Inhibidores Enzimáticos/metabolismo , Lisina/metabolismo , Espectrometría de Masas , Datos de Secuencia Molecular , Estructura Molecular , Pentosiltransferasa/química , Alineación de SecuenciaRESUMEN
Derivatives of 3'-deoxythymidine (ddT) and 3'-deoxy-2',3'-didehydrothymidine (d4T) were prepared in which the 5'-hydroxyl group of the nucleoside was esterified to a bis-ketol phosphate. The resulting phosphate triesters are postulated to be prodrugs of the corresponding 5'-mononucleotides, which are formed intracellularly by the hydrolysis of the two ketol ester groups. The triesters were tested for anti-HIV activity with the result that those derived from ddT showed enhanced antiviral activity when compared to the parent nucleoside.
