The Acyclic 2,4-Diaminopyrimidine Nucleoside Phosphonate Acts as a Purine Mimetic in HIV-1 Reverse Transcriptase DNA Polymerization

0343318 - ÚOCHB 2011 RIV US eng J - Journal Article
Herman, B. D. - Votruba, Ivan - Holý, Antonín - Sluis-Cremer, N. - Balzarini, J.
The Acyclic 2,4-Diaminopyrimidine Nucleoside Phosphonate Acts as a Purine Mimetic in HIV-1 Reverse Transcriptase DNA Polymerization.
Journal of Biological Chemistry. Roč. 285, č. 16 (2010), s. 12101-12108. ISSN 0021-9258. E-ISSN 1083-351X
Grant - others:NIH(US) R01 AI81571; KU Leuven(BE) GOA Kredit 05/19
Institutional research plan: CEZ:AV0Z40550506
Keywords : acyclic nucleotide analogue * purine open ring * HIV-1 RT * antiviral * antimetabolite
Subject RIV: CC - Organic Chemistry
Impact factor: 5.328, year: 2010

HIV-1 RT recognizes diphosphate of the acyclic pyrimidine nucleoside phosphonate (ANP) phosphonylmethoxyethoxydiaminopyrimidine (PMEO-DAPym) as purine nucleotide analogue. Molecular modeling demonstrates that PMEO-DAPym-pp fits into the active site of HIV-1 RT and incorporates opposite to thymine (in DNA). The data revealed that PMEODAPym represents the prototype compound of a novel class of pyrimidine acyclic nucleoside phosphonates and should form the rational basis for the design and development of novel purine nucleo(s)(t)ide mimetics as potential antiviral or antimetabolic agents.
Permanent Link: http://hdl.handle.net/11104/0185824