180187-93-3Relevant academic research and scientific papers
Potential application of thymidylate kinase in nucleoside analogue activation in Plasmodium falciparum
Cui, Huaqing,Ruiz-Pérez, Luis M.,González-Pacanowska, Dolores,Gilbert, Ian H.
experimental part, p. 7302 - 7309 (2010/11/18)
Plasmodium falciparum thymidylate kinase (PfTMPK) shows a broad range of substrate tolerance when compared to the corresponding human enzyme. Besides 2′-deoxythymidine monophosphate (dTMP), PfTMPK can phosphorylate 3′-azido-2′,3′-dideoxythymidine monophos
Protease-mediated enzymatic hydrolysis and activation of aryl phosphoramidate derivatives of stavudine
Venkatachalam,Samuel,Qazi,Uckun
, p. 452 - 466 (2007/10/03)
Several proteases are capable of hydrolyzing the aryl substituted phosphoramidate derivatives of stavudine resulting in the formation of the active metabolite, alaninyl d4T monophosphate. Subtilisin Protease A, Subtilisin Griseus, Subtilisin Carlsberg, Papaya, Bacillus were amongst the most effective proteases in hydrolyzing stavudine derivatives and specificity of their activity was confirmed using several protease inhibitors to block the hydrolysis of these phosphoramidate derivatives. We found that these proteases exhibit chiral selectivity at the phosphorus center of stavudine derivatives. Our results indicate that cellular proteases may be responsible for the activation of these phosphoramidate derivatives. In addition, we show that the enzymatic hydrolysis takes place at the carboxymethyl ester side chain of these pro-drugs and the direct attack on the phosphorus center by these enzymes does not occur. Finally, we describe a novel activation pathway hitherto unknown for the activation and viral inhibitory characteristic shown by these phosphoramidate derivatives of stavudine.
Stereochemical influence on lipase-mediated hydrolysis and biological activity of stampidine and other stavudine phosphoramidates
Venkatachalam,Samuel,Uckun
, p. 1763 - 1773 (2008/02/02)
Stampidine and other halogen substituted stavudine phosphoramidates can be activated by lipase-mediated hydrolysis. The target site for the lipase appears to be the methyl ester group of the L-alanine side chain. Accordingly, the D-amino acid substituted
Aryl phosphate derivatives of d4T having anti-HIV activity
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Page column 4-5, (2008/06/13)
Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.
