Synthesis, characterization and some properties of dideoxynucleoside analogs of cytidine diphosphate diacylglycerol.
Phospholipid conjugates of antiretroviral nucleoside analogs have been proposed to have several advantageous features when compared to the parent drugs (Hostetler, K.Y. et al. (1990) J. Biol. Chem. 265, 6112-6117). Here we report on the synthesis of one such type of lipid conjugates, i.e., nucleosides diphosphate diacylglycerols. The syntheses of 3'-azido-3'-deoxythymidine diphosphate diacylglycerol, 3'-deoxythymidine diphosphate diacylglycerol and 2',3'-dideoxycytidine diphosphate diacylglycerol (with different acyl chains) were performed starting from phosphatidic acid and the antiviral nucleoside. A high-performance liquid chromatography procedure for a single step purification of the compounds is presented. The compounds were characterized biochemically, using rat liver enzymes and chemically by phosphorus, fatty acid, ultraviolet, IR and 1H-NMR analyses. Preliminary data on the behaviour in aqueous solution of some of the compounds are presented.
van Wijk
G M
GM
Center for Biomembranes and Lipid Enzymology, University of Utrecht, Netherlands.
Hostetler
K Y
KY
Suurmeijer
C N
CN
van den Bosch
H
H
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004075:Diglycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D006678:HIV / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
D000998:Antiviral Agents; D003845:Deoxycytosine Nucleotides; D004075:Diglycerides; D013942:Thymine Nucleotides