Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

The ability of monophosphates of selected acyclic nucleoside phosphonates to serve as substrates for the title NDP kinases was studied. Comparison of the kinetic constants (K_M, V_max, k_cat and k_cat/K_M) estimates indicates that the yeast enzyme catalyzes the phosphorylation of purine and pyrimidine acyclic nucleoside phosphate phosphonates of the 9-[2-(phosphonomethoxy)ethyl] and/or 9-[2-(phosphonomethoxy)propyl] series more efficiently than bovine liver NDP kinase. Yeast enzyme preferentially phosphorylates phosphates of the (phosphono- methoxyalkyl)guanines rather than their adenine counterparts; both enzymes phosphorylate R-enantiomers of the 9-[2-(phosphonomethoxy)propyl] series more efficiently than the corresponding S-enantiomers. Substitution of the aliphatic chain at the position 3 with hydroxymethyl group considerably increases the substrate activity of phosphate of acyclic nucleoside phosphonate. The resulting substrate activity (k_cat/K_M ratio) of all acyclic nucleoside phosphonate phosphates studied is three to five orders of magnitude lower than that for natural NDPs.

Keywords: Enzymatic phosphorylation; Phosphates in acyclic nucleoside phosphonates; Acyclic nucleotide analogs; NTP analogues; NDP kinase; PMEAp; (R)-PMPAp; Antivirals.

References: 21 live references.