Synthesis of two diastereoisomeric p-nitrophenyl phosphodiesters of 2',3'-secouridine and their affinity for phosphodiesterases.
The synthesis of the p-nitrophenyl esters of the 5'- and 3'-phosphates of the nucleoside analogue 2',3'-secouridine are described. Unlike the corresponding diesters of thymidine, these two compounds are diastereoisomers. Their affinity for phosphodiesterases types I and II were investigated. Both analogues were hydrolysed very slowly by snake venom phosphodiesterase but their affinity for the enzyme was similar to that of the p-nitrophenyl ester of thymidine 5'-monophosphate of which they were both competitive inhibitors with Ki approximately Km. Neither compound was hydrolysed by spleen phosphodiesterase but both competitively inhibited the p-nitrophenyl ester of thymidine 3'-monophosphate, with Ki's slightly higher than the Km. Although for each enzyme the Ki of the correct analogue phosphodiester (i.e. the 5'-derivative for snake venom and the 3'-derivative for spleen) was the lower, the absolute specificity seen for the normal substrates had been lost.
D000345:Affinity Labels; D055598:Chemical Phenomena; D002621:Chemistry; D003435:Crotalid Venoms; D006868:Hydrolysis; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity; D014500:Uracil Nucleotides / Q000138:chemical synthesis*; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis
D000345:Affinity Labels; D003435:Crotalid Venoms; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D014500:Uracil Nucleotides; C049762:2',3'-secouridine 4-nitrophenyl 5'-phosphate; C049765:2',3'-secouridine 4-nitrophenyl 3'-phosphate; C008644:nitrophenylphosphate; D014542:Uridine Monophosphate; D010727:Phosphoric Diester Hydrolases