title: The 2',3'-dideoxyriboside of 2,6-diaminopurine and its 2',3'-didehydro derivative inhibit the deamination of 2',3'-dideoxyadenosine, an inhibitor of human immunodeficiency virus (HIV) replication.
abstract: The 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) and its 2',3'-didehydro derivative (ddeDAPR) are poor substrates for adenosine deaminase (ADA) but potent inhibitors of the enzyme. Their Km values for ADA are of the same order of magnitude as those of the natural adenosine (Ado) and 2'-deoxyadenosine (dAdo), but their Vmax values are 35-fold (ddDAPR) to 350-fold (ddeDAPR) lower than those of Ado and dAdo. The Ki/K values of ADA for ddeDAPR (as inhibitor) and Ado, 2',3'-dideoxyadenosine (ddAdo) and 9-beta-D-arabinofuranosyladenine (araA) as the substrates are 0.17, 0.05 and 0.06, respectively. ddDAPR is about 3-fold less potent as an inhibitor of ADA than ddeDAPR. The 2,6-diaminopurine derivatives ddeDAPR and ddDAPR [which is also a potent inhibitor of human immunodeficiency virus (HIV)], may hold great promise, from a chemotherapeutic viewpoint, in combination with other adenosine analogues such as ddAdo and araA, which have been recognized and/or being pursued as either anti-retrovirus or anti-herpesvirus agents.
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004261:DNA Replication / Q000187:drug effects*; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives; D015224:Dideoxynucleosides; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D007422:Intestines / Q000201:enzymology; D007700:Kinetics; D009700:Nucleoside Deaminases / Q000378:metabolism*; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects
chemical_list: D003839:Deoxyadenosines; D015224:Dideoxynucleosides; C052692:2,6-diaminopurine 2',3'-dideoxyriboside; C052693:2,6-diaminopurine 2',3'-didehydro-2',3'-dideoxyriboside; D016048:Dideoxyadenosine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase