Actions of purine analogs: enzyme specificity studies as a basis for interpretation and design.

The importance of quantitative studies of the specificities of purine-metabolizing enzymes are discussed. These data not only enable one to make predictions concerning the metabolic disposition and effectiveness of a drug in vivo , but they also help to identify its loci of action. They may also serve as a basis for understanding the selective toxicity of a compound and aid in the design of new antimetabolites.

[1]  J. Wyngaarden,et al.  PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES. , 1964, The Journal of biological chemistry.

[2]  R. Parks,et al.  Adenosine triphosphate-guanosine 5'-phosphate phosphotransferase. II. Inhibition by 6-thioguanosine 5'-phosphate of the enzyme isolated from hog brain and sarcoma 180 ascites cells. , 1969, Molecular pharmacology.

[3]  I. Fridovich,et al.  Adenine aminohydrolase. An investigation of specificity. , 1967, The Journal of biological chemistry.

[4]  V H Booth,et al.  The specificity of xanthine oxidase. , 1938, The Biochemical journal.

[5]  J. Montgomery,et al.  Purine ribonucleoside kinase activity and resistance to some analogs of adenosine. , 1966, Molecular pharmacology.

[6]  G. Lepage,et al.  METABOLISM OF PURINE NUCLEOSIDE ANALOGS. , 1965, Cancer research.

[7]  G. Hitchings,et al.  Metabolic basis for the actions of analogs of purines and pyrimidines. , 1965, Advances in chemotherapy.

[8]  D. Blair.  Adenylate and 2,6-diaminopurine ribonucleotide pyrophosphorylase activities of L cells. , 1967, Canadian journal of biochemistry.

[9]  S. Frederiksen.  Specificity of adenosine deaminase toward adenosine and 2'-deoxyadenosine analogues. , 1966, Archives of biochemistry and biophysics.

[10]  H. Shigeura,et al.  Structural Basis for Phosphorylation of Adenosine Congeners , 1967, Nature.

[11]  J. Wyngaarden,et al.  6-Mercaptopurine as substrate and inhibitor of xanthine oxidase , 1961 .

[12]  J. G. Cory,et al.  Structural Requirements of Nucleosides for Binding by Adenosine Deaminase , 1965 .

[13]  G. J. Dixon,et al.  Activity and Mechanism of Action of 6-Methylthiopurine Ribonucleoside in Cancer Cells Resistant to 6-Mercaptopurine , 1965, Nature.

[14]  J. Brink,et al.  METABOLIC EFFECTS OF 9-D-ARABINOSYLPURINES IN ASCITES TUMOR CELLS. , 1964, Cancer research.

[15]  G. Hitchings,et al.  The Identification of Guanine in Extracts of Girella Nigricans: The Specificity of Guanase. , 1944, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A. Kornberg,et al.  Enzymatic phosphorylation of adenosine and 2,6-diaminopurine riboside. , 1951, The Journal of biological chemistry.

[17]  R. Miller,et al.  Substrate binding specificity and properties of inosine monophosphate: pyrophosphate phosphoribosyltransferase (EC 2.4.2.8) from Brewers yeast. , 1969, Biochemistry.

[18]  Felix Bergmann,et al.  The action of mammalian xanthine oxidase on N-methylated purines. , 1960 .

[19]  L. Bennett,et al.  Metabolic studies with carbocyclic analogs of purine nucleosides. , 1968, Molecular pharmacology.

[20]  G. Elion,et al.  Human hypoxanthine phosphoribosyltransferase. I. Purification, properties, and specificity. , 1969, The Journal of biological chemistry.

[21]  A. Paterson,et al.  The enzymic formation of 6-(methylmercapto)purine ribonucleoside 5'-phosphate. , 1966, Canadian journal of biochemistry.

[22]  J. G. Cory,et al.  Dechloronase Activity of Adenosine Deaminase , 1965 .

[23]  M. Baliś,et al.  THE MECHANISM OF ACTION OF 6-MERCAPTOPURINE. I. BIOCHEMICAL EFFECTS. , 1965, Cancer research.

[24]  A. W. Murray,et al.  INHIBITION OF INOSINE 5'-PHOSPHATE DEHYDROGENASE FROM EHRLICH ASCITES-TUMOUR CELLS BY 6-THIONINOSINE 5'-PHOSPHATE. , 1963, The Biochemical journal.

[25]  A. Hampton.  REACTIONS OF RIBONUCLEOTIDE DERIVATIVES OF PURINE ANALOGUES AT THE CATALYTIC SITE OF INOSINE 5'-PHOSPHATE DEHYDROGENASE. , 1963, The Journal of biological chemistry.

[26]  B. Chassy,et al.  Nucleoside antibiotics. II. Biochemical tools for studying the structural requirements for interaction at the catalytic and regulatory sites of ribonucleotide reductase from Escherichia coli. , 1968, The Journal of biological chemistry.

[27]  G. Hitchings,et al.  Potentiation by inhibition of drug degradation : 6-substituted purines and xanthine oxidase , 1963 .

[28]  B. Chassy,et al.  Adenosine aminohydrolase. Binding and hydrolysis of 2-and 6-substituted purine ribonucleosides and 9-substituted adenine nucleosides. , 1967, The Journal of biological chemistry.

[29]  M. Maguire,et al.  Studies on adenosine deaminase. I. Purification and properties of ox heart adenosine deaminase. , 1966, Molecular pharmacology.

[30]  A. W. Murray,et al.  Inhibition of adenylosuccinate synthetase and adenylosuccinate lyase from Ehrlich ascites-tumour cells by 6-thioinosine 5'-phosphate. , 1964, The Biochemical journal.

[31]  D. Hill,et al.  Purification and properties of adenosine kinase from human tumor cells of type H. Ep. No. 2. , 1967, The Journal of biological chemistry.

[32]  J. L. Way,et al.  Enzymatic synthesis of 5'-phosphate nucleotides of purine analogues. , 1958, The Journal of biological chemistry.

[33]  G. Hitchings,et al.  Metabolic studies of allopurinol, an inhibitor of xanthine oxidase. , 1966, Biochemical pharmacology.

[34]  G. Hitchings,et al.  Inhibition of human purine nucleoside phosphorylase. Studies with intact erythrocytes and the purified enzyme. , 1968, The Journal of biological chemistry.

[35]  L. Lukens,et al.  Enzymic formation of 6-mercaptopurine tibo tide. , 1957, Biochimica et biophysica acta.

[36]  M. Mansoor,et al.  BRAIN GUANINE DEAMINASE: PURIFICATION, PROPERTIES AND REGIONAL DISTRIBUTION. , 1963, Biochimica et biophysica acta.

[37]  B. R. Baker.  Irreversible enzyme inhibitors. 93. Hydrophobic bonding to xanthine oxidase by some phenylpurines. , 1967, Journal of pharmaceutical sciences.

[38]  J. Mccarthy,et al.  The role of the 5'-hydroxyl group of adenosine in determining substrate specificity for adenosine deaminase. , 1967, Journal of medicinal chemistry.

[39]  A. Hampton,et al.  Inosine 5'-phosphate dehydrogenase. Site of inhibition by guanosine 5'-phosphate and of inactivation by 6-chloro- and 6-mercaptopurine ribonucleoside 5'-phosphates. , 1967, Biochemistry.

[40]  A. Sartorelli,et al.  An hypothesis on the mechanism of action of 6-thioguanine. , 1967, Biochemical pharmacology.

[41]  G. Elion.  Enzymatic and Metabolic Studies with Allopurinol , 1966, Annals of the rheumatic diseases.

[42]  K. J. Pierre,et al.  The effect of structure on nucleoside kinase activity. , 1967, Canadian journal of biochemistry.

[43]  C. A. Nichol,et al.  On the mode of action of 7-deaza-adenosine (tubercidin). , 1967, Biochimica et biophysica acta.

[44]  H. Skipper,et al.  Searches for exploitable biochemical differences between normal and cancer cells. V. Cellular conservation of purines. , 1960, Cancer research.

[45]  G. Hitchings,et al.  Thioguanine in Deoxyribonucleic Acid from Tumors of 6-Mercaptopurine-Treated Mice , 1966, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[46]  M. Baliś,et al.  THE MECHANISM OF ACTION OF 6-MERCAPTOPURINE. II. BASIS FOR SPECIFICITY. , 1965, Cancer research.

[47]  F. Bergmann,et al.  Studies on the enzymic oxidation of aminopurines. , 1960, Biochimica et biophysica acta.

[48]  L. Bennett,et al.  Conversion of 6-mercaptopurine and 6-mercaptopurine ribonucleoside to 6-methylmercaptopurine ribonucleotide in human epidermoid carcinoma no. 2. cells in culture. , 1966, Biochimica et biophysica acta.

[49]  P. Re,et al.  ADENOSINE TRIPHOSPHATE: GUANOSINE MONOPHOSPHATE PHOSPHOTRANSFERASE. PARTIAL PURIFICATION AND SUBSTRATE SPECIFICITY. , 1965, The Journal of biological chemistry.

[50]  R. K. Robins,et al.  Pyrazolopyrimidines as inhibitors and substrates of xanthine oxidase. , 1957, The Journal of biological chemistry.

[51]  G. Hitchings,et al.  Studies on Condensed Pyrimidine Systems. XXI. The Isolation and Synthesis of 6-Mercapto-2,8-purinediol (6-Thiouric Acid) , 1959 .

[52]  D. E. Duggan,et al.  6-Chloropurine and 6-chlorouric acid as substrates and inhibitors of purine-oxidizing enzymes. , 1959, The Journal of biological chemistry.

[53]  B. Chassy,et al.  Nucleoside antibiotics. I. Biochemical tools for studying the structural requirements for interaction at the catalytic and regulatory sites of ribonucleotide reductase from Lactobacillus leichmannii. , 1968, The Journal of biological chemistry.

[54]  T. Krenitsky.  Purine nucleoside phosphorylase: kinetics, mechanism, and specificity. , 1967, Molecular pharmacology.

[55]  A. Paterson,et al.  Biochemical effects of formycin, an adenosine analog. , 1967, Cancer research.