Metabolic properties of phosphonate esters.
The object of the present work was to investigate the difference in the metabolism of the phosphonate derivatives of primary or secondary hydroxyl groups. To study the phosphorolytic cleavage of such P-O bonds, zidovudine (AZT) hexanoyloxymethyl-methylphosphonate (HOM-AZT-P), an ester of a primary OH functionality, and methyl-pivaloyloxymethyl-testosterylphosphonate (POM-T-P), an ester of a secondary OH functionality, were prepared. The actions of pure enzymes such as alkaline phosphatase and phosphodiesterase on the corresponding phosphonate compounds (AZT-P and T-P) were investigated at various pH values. The phosphonate derivative of the secondary hydroxyl group of testosterone proved completely resistant to such phosphorolytic attacks, and release of free testosterone could not be detected. The phosphonate derivative of the primary hydroxyl group of zidovudine proved resistant to phosphodiesterase, but not to alkaline phosphatase, and in this second case, release of free zidovudine could be detected.
Somogyi
G
G
Institute of Forensic Medicine, University of Debrecen, Medical and Health Science Center, Hungary. gsomogyi@jaguar.dote.hu
Buchwald
P
P
Bodor
N
N
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004952:Esters / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D063065:Organophosphonates / Q000378:metabolism*; D015215:Zidovudine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism
D019380:Anti-HIV Agents; D004952:Esters; D063065:Organophosphonates; D015215:Zidovudine; D000469:Alkaline Phosphatase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4