BIOMAT Database Logo BIOMAT Database Logo

Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity. 1992

W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Division of Experimental Therapy, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.

Two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were compared with respect to their phosphorylation and the phosphorylation of their nucleotides by mammalian enzymes. 5'-Nucleotidase catalyzed the phosphorylation of (-)-carbovir, which is active against HIV (human immunodeficiency virus), but did not phosphorylate (+)-carbovir. (-)-Carbovir monophosphate was 7,000 times more efficient as a substrate for GMP kinase than was (+)-carbovir monophosphate. Pyruvate kinase, phosphoglycerate kinase, and creatine kinase phosphorylated both enantiomers of carbovir diphosphate at similar rates. Nucleoside-diphosphate kinase preferentially phosphorylated the (-)-enantiomer. Both enantiomers of carbovir triphosphate were substrates and alternative substrate inhibitors of HIV reverse transcriptase. Thus, the contrasting HIV-inhibitory activities of carbovir enantiomers were due to differential phosphorylation by cellular enzymes and not due to enantioselectivity of HIV reverse transcriptase.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009703 Nucleoside-Phosphate Kinase An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4. Nucleoside Monophosphate Kinases,Kinase, Nucleoside-Phosphate,Kinases, Nucleoside Monophosphate,Monophosphate Kinases, Nucleoside,Nucleoside Phosphate Kinase
D010729 Phosphoenolpyruvate Carboxykinase (GTP) An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32. GTP-Dependent Phosphoenolpyruvate Carboxykinase,Carboxykinase, GTP-Dependent Phosphoenolpyruvate,GTP Dependent Phosphoenolpyruvate Carboxykinase,Phosphoenolpyruvate Carboxykinase, GTP-Dependent
D010735 Phosphoglycerate Kinase An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3. Kinase, Phosphoglycerate
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010770 Phosphotransferases A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7. Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D011770 Pyruvate Kinase ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. L-Type Pyruvate Kinase,M-Type Pyruvate Kinase,M1-Type Pyruvate Kinase,M2-Type Pyruvate Kinase,Pyruvate Kinase L,R-Type Pyruvate Kinase,L Type Pyruvate Kinase,M Type Pyruvate Kinase,M1 Type Pyruvate Kinase,M2 Type Pyruvate Kinase,Pyruvate Kinase, L-Type,Pyruvate Kinase, M-Type,Pyruvate Kinase, M1-Type,Pyruvate Kinase, M2-Type,Pyruvate Kinase, R-Type,R Type Pyruvate Kinase
D003402 Creatine Kinase A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. Creatine Phosphokinase,ADP Phosphocreatine Phosphotransferase,ATP Creatine Phosphotransferase,Macro-Creatine Kinase,Creatine Phosphotransferase, ATP,Kinase, Creatine,Macro Creatine Kinase,Phosphocreatine Phosphotransferase, ADP,Phosphokinase, Creatine,Phosphotransferase, ADP Phosphocreatine,Phosphotransferase, ATP Creatine
D003848 Deoxyguanine Nucleotides Guanine nucleotides which contain deoxyribose as the sugar moiety. Deoxyguanosine Phosphates,Nucleotides, Deoxyguanine,Phosphates, Deoxyguanosine

Related Publications

W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Phosphorylation of ganciclovir phosphonate by cellular GMP kinase determines the stereoselectivity of anti-human cytomegalovirus activity.
January 2000, Nucleosides, nucleotides & nucleic acids,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Antiviral activity of cyclosaligenyl prodrugs of acyclovir, carbovir and abacavir.
September 2001, Antiviral chemistry & chemotherapy,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Phosphorylation of acyclovir diphosphate by cellular enzymes.
December 1982, Biochemical pharmacology,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Physicochemical characterization of the various solid forms of carbovir, an antiviral nucleoside.
August 1994, Journal of pharmaceutical sciences,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Stereoselectivity of channel inhibition by secondary alkanol enantiomers at nicotinic acetylcholine receptors.
July 1993, Anesthesiology,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Species variation and stereoselectivity in the metabolism of nicotine enantiomers.
December 1988, Xenobiotica; the fate of foreign compounds in biological systems,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Stereoselectivity of paclobutrazol enantiomers to oxidative stress in wheat.
February 2024, Chirality,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Synthesis of novel 2'-methyl carbovir analogues as potent antiviral agents.
February 2007, Archives of pharmacal research,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
CK2-dependent phosphorylation determines cellular localization and stability of ataxin-3.
September 2009, Human molecular genetics,
W H Miller, and S M Daluge, and E P Garvey, and S Hopkins, and J E Reardon, and F L Boyd, and R L Miller
Stereoselectivity in the hydroxylation of propafenone enantiomers in mouse hepatic microsomes.
April 1994, Biological & pharmaceutical bulletin,
Copied contents to your clipboard!