Lipid conjugates of antiretroviral agents: release of antiretroviral nucleoside monophosphates by a nucleoside diphosphate diglyceride hydrolase activity from rat liver mitochondria.
The release of the 5'-monophosphates of the antiretroviral nucleoside analogs 3'-azido-3'-deoxythymidine, 3'-deoxythymidine and 2',3'-dideoxycytidine from the corresponding nucleoside diphosphate diglycerides as a result of rat liver mitochondrial enzymatic activity is shown. The three analogs appeared to be about equally active as substrate for this pyrophosphatase activity which showed maximum conversion rates of 3-6 nmol min-1 mg protein-1 at substrate concentrations between 500 to 800 microM. These results may contribute to the biochemical explanation for the observed anti-HIV activity of this type of phospholipid conjugates in vitro.
van Wijk
G M
GM
Centre for Biomembranes and Lipid Enzymology, University of Utrecht, The Netherlands.
Hostetler
K Y
KY
van den Bosch
H
H
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism*; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006868:Hydrolysis; D050356:Lipid Metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011755:Pyrophosphatases / Q000378:metabolism*; D051381:Rats; D013942:Thymine Nucleotides; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000378:metabolism
D000998:Antiviral Agents; D002308:Cardiolipins; D004075:Diglycerides; D013942:Thymine Nucleotides; D015215:Zidovudine; D011755:Pyrophosphatases