114088-58-3Relevant articles and documents
Human N6-methyl-AMP/dAMP aminohydrolase (abacavir 5-monophosphate deaminase) is capable of metabolizing N6-substituted purine acyclic nucleoside phosphonates
Schinkmanova, Marketa,Votruba, Ivan,Shibata, Riri,Han, Bin,Liu, Xiaohong,Cihlar, Tomas,Holy, Antonin
, p. 275 - 291 (2008)
Recombinant human abacavir monophosphate deaminase (hABC-MP deaminase) was compared with the recently described rat N6-methyl-AMP (meAMP) aminohydrolase. hABC-MP deaminase, a 42 kDa polypeptide, exists predominantly as a monomer under non-denaturing conditions. Similar to the rat enzyme, hABC-MP deaminase efficiently catalyzes the hydrolytic deamination of natural substrates meAMP (5), N6,N6-dimethyl-AMP (13) and medAMP (6). Acyclic nucleoside phosphonate (ANP) N6-cyclopropyl-2,6-diamino-9-[2- (phosphonomethoxy)ethyl]purine (cPrPMEDAP) (1), an intermediate intracellular metabolite of antileukemic agent GS-9219, was effectively converted to the corresponding active guanine analog by hABC-MP deaminase. In addition to cPrPMEDAP (1), a number of other biologically active N6-substituted purine ANPs are alternative substrates for hABC-MP deaminase. The efficiency of their deamination depends on the character of N6-substitution in the adenine and/or 2,6-diaminopurine ring. ANPs with N6-cyclic substituents are deaminated more readily than corresponding compounds with aliphatic substituents of the same length. The deamination of ANPs is also influenced by modifications at the phosphonoalkyl side chain. Among 9-[2-(phosphonomethoxy)propyl] ANPs, (S)-enantiomers are preferred to (R)-enantiomers. Alternatively, the presence of extended 9-[2-(phosphonoethoxy) ethyl] moiety leads to a moderate increase in the reaction velocity compared to cPrPMEDAP (1). Comparison of hABC-MP deaminase and the rat meAMP aminohydrolase across a broad spectrum of N6-substituted substrates revealed a strong correlation of their substrate specificities. Similar to the rat meAMP aminohydrolase, hABC-MP deaminase was highly sensitive to deoxycoformycin monophosphate, but not to the guanine product of cPrPMEDAP (1) deamination. Together, these data demonstrate that hABC-MP deaminase is human meAMP aminohydrolase involved in the intracellular activation of biologically active N6-substituted nucleotide analogs.
NUCLEOTIDE ANALOGS
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Paragraph 0197; 0198, (2017/04/11)
Disclosed herein, inter alia, are acyclic nucleotide analogs and methods of using an acyclic nucleotide analog for treating and/or ameliorating a papillomavirus infection.
Microwave-assisted hydrolysis of phosphonate diesters: An efficient protocol for the preparation of phosphonic acids
Jansa, Petr,Baszczynski, Ondrej,Prochazkova, Eliska,Dracinsky, Martin,Janeba, Zlatko
supporting information; experimental part, p. 2282 - 2288 (2012/09/08)
A new highly efficient method for the hydrolysis of acyclic nucleoside phosphonate diesters (or generally of any organophosphonates) to the corresponding phosphonic acids has been developed. This novel methodology employs inexpensive hydrochloric acid in equimolar amounts to the number of ester groups present in the molecule and thus, avoids using trimethylsilyl halogenides, the standard reagents for these types of transformations. Moreover, simple and easy work-up of the reaction mixture affords very clean products in high yields (usually 77-93%). Another advantage of the described hydrolysis of phosphonate diesters is the fact that the course of the reaction can be instantly monitored through pressure changes in the reaction vessel. This 'green' method has also been successfully used for the preparation of otherwise synthetically difficult to access (phosphonomethoxy)ethyl (PME) derivatives of guanine (PMEG) and hypoxanthine (PMEHx), and furthermore, the method gains access to important novel acyclic nucleoside phosphonates derived from 2-chlorohypoxanthine and from xanthine (e.g. PMEX).
