Synthesis of 2',3'-dideoxynucleosides by enzymatic trans-glycosylation.
Recently, several pyrimidine and purine 2',3'-dideoxynucleosides have been shown to inhibit the replication of the human immunodeficiency virus-1 (HIV), the causative agent of the acquired immune deficiency syndrome (AIDS). These compounds are usually prepared by reduction of the corresponding 2'-deoxynucleosides. The present experiments demonstrate that 2',3'-dideoxynucleosides can also be made by enzymatic trans-glycosylation, using the trans-N-deoxyribosylase from Lactobacillus helveticus. The broad specificity of this enzyme makes it possible to synthesize for metabolic studies radiochemically pure 2',3'-dideoxynucleosides, using diverse purine and pyrimidine base acceptors.
Carson
D A
DA
Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Wasson
D B
DB
D000998:Antiviral Agents / Q000032:analysis*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000096:biosynthesis; D003853:Deoxyribonucleosides / Q000096:biosynthesis*; D016048:Dideoxyadenosine; D006031:Glycosylation; D006678:HIV / Q000187:drug effects; D007700:Kinetics; D007778:Lactobacillus / Q000201:enzymology; D010430:Pentosyltransferases / Q000378:metabolism*; D013379:Substrate Specificity
D000998:Antiviral Agents; D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D016048:Dideoxyadenosine; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase