N6-methyl-AMP aminohydrolase activates N6-substituted purine acyclic nucleoside phosphonates
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16513094
DOI
10.1016/j.bcp.2006.01.013
PII: S0006-2952(06)00065-7
Knihovny.cz E-resources
- MeSH
- Adenine metabolism MeSH
- Aminohydrolases isolation & purification metabolism MeSH
- Electrophoresis, Polyacrylamide Gel MeSH
- Guanine analogs & derivatives metabolism MeSH
- Liver enzymology MeSH
- Catalysis MeSH
- Rats MeSH
- Organophosphonates metabolism MeSH
- Organophosphorus Compounds metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Prodrugs metabolism MeSH
- In Vitro Techniques MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 9-((2-phosphonylmethoxy)ethyl)guanine MeSH Browser
- Adenine MeSH
- Aminohydrolases MeSH
- Guanine MeSH
- N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Browser
- Organophosphonates MeSH
- Organophosphorus Compounds MeSH
- Prodrugs MeSH
In this study we present the identification and characterization of the enzyme involved in the N6-cyclopropyl-2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (N6-cyclopropyl-PMEDAP) conversion to biologically active 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) as well as abacavir 5'-phosphate to carbovir 5'-phosphate. This enzyme was purified from rat liver to homogeneity; it appears to be composed from six 42 kDa subunits and its native form has the molecular weight 260 kDa. This so far unknown enzyme catalyzes conversion of both N6-methyl-AMP and N6-methyl-dAMP to IMP and/or dIMP, respectively. The enzyme acts as 6-(N-substituted amino)purine 5'-nucleotide aminohydrolase with the reaction mechanism very similar to AMP deaminase. The enzyme does not deaminate AMP and dAMP, or the corresponding nucleosides. It is inhibited by deoxycoformycin 5'-phosphate but not by deoxycoformycin or erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA).
References provided by Crossref.org
Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects
