Collect. Czech. Chem. Commun.
2000, 65, 1653-1668
https://doi.org/10.1135/cccc20001653
Phosphorylation of Purine (Phosphonomethoxy)alkyl Derivatives by Mitochondrial AMP Kinase (AK2 Type) from L1210 Cells
Romana Krejčová, Květoslava Horská, Ivan Votruba* and Antonín Holý
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
Abstract
Substrate activity of purine (phosphonomethoxy)alkyl derivatives towards mitochondrial AMP kinase (AK2 type) from L1210 cells was studied. The native AMP kinase, purified nearly to homogeneity, is a monomer with molecular weight 26 kDa. The purified AMP kinase is specific for natural adenine nucleotides (AMP and dAMP) as phosphate acceptors but has a broad specificity to nucleoside 5'-triphosphates as phosphate donors. In addition to adenine acyclic nucleotide analogues, the enzyme is capable of phosphorylating also analogous derivatives containing 2,6-diaminopurine moiety. Kinetic data show that the substrate activity of these acyclic nucleoside phosphonates towards AK2 isoenzyme decreases in the order (S)-HPMPA > (R)-PMPA > PMEA > PMEDAP > (S)-PMPDAP > (R)-PMPDAP >> (S)-PMPA. Acyclic nucleotide analogues do not exhibit any inhibitory activity towards AK2 isoenzyme.
Keywords: Enzymatic phosphorylation; Acyclic nucleotide analogues; Nucleotides; Phosphonates; Phosphates; AMP kinase; AK2; L1210 cells; PMEA; PMPA; PMEDAP; Antivirals.
References: 50 live references.
