title: Phosphorylation of 9-(2-phosphonomethoxyethyl)adenine and 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)adenine by AMP(dAMP) kinase from L1210 cells.
abstract: Acyclic nucleotide analogues 9-(2-phosphonomethoxyethyl)adenine (PMEA) and 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)adenine ((S)-HPMPA) which display potent antiviral activity are transformed in the cells to their mono- and disphosphoryl derivatives. We purified from mouse L1210 cells the enzyme that in two steps phosphorylates PMEA and (S)-HPMPA to their diphosphoryl derivatives and found that it co-purifies with AMP(dAMP) kinase activity; the best substrates of this enzyme were AMP, ADP and dAMP. Other nucleoside 5'-triphosphates or creatine phosphate could not be substituted for ATP as a phosphate donor. Our results also indicated that at least one other enzyme (creatine kinase) is capable of transforming the monophosphoryl derivatives of the studied compounds to their respective diphosphates.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague.
authors.forename: A
authors.initials: A
authors.lastname: Merta
authors.forename: I
authors.initials: I
authors.lastname: Votruba
authors.forename: J
authors.initials: J
authors.lastname: Jindrich
authors.forename: A
authors.initials: A
authors.lastname: Holý
authors.forename: T
authors.initials: T
authors.lastname: Cihlár
authors.forename: I
authors.initials: I
authors.lastname: Rosenberg
authors.forename: M
authors.initials: M
authors.lastname: Otmar
authors.forename: T Y
authors.initials: TY
authors.lastname: Herve
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000263:Adenylate Kinase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D007526:Isoelectric Point; D007939:Leukemia L1210 / Q000201:enzymology*; D051379:Mice; D008970:Molecular Weight; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism*; D013379:Substrate Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D063065:Organophosphonates; D009943:Organophosphorus Compounds; C053001:adefovir; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D003402:Creatine Kinase; D000263:Adenylate Kinase; D000225:Adenine