Cyclic phosphates of some antiviral acyclonucleosides: relationship between conformation and substrate-inhibitor properties in some enzyme systems

• Autorzy: Ciesla J. M. , Stolarski R. , Shugar D.
• Języki publikacji: EN

Abstrakty

Solution conformations, and substrate/inhibitor properties towards several phosphodiesterases and other nucleolytic enzymes, have been investigated for the cyclic phosphates of various acyclonucleosides, some with known antiviral activity, including 9-[(l,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and its carbocyclic congener, 9-(3,4-dihydroxybutyl)guanine (DHBG), 9-[4-hydroxy-2-(hydroxymethyl)- butyl]-guanine (2HM-HBG), and 9-(2,3-dihydroxypropyl)guanine (HPG). Conformations of the cyclic phosphate rings were derived from analysis of the 1H-1H and 1H-31P vicinal coupling constants in the n.m.r. spectra, subsequently optimalized by minimalization of the internal energy. The resulting structures were examined with respect to their ability to recognize various specific phosphodiesterases and nucleases, and some structural parameters were delineated for acyclonucleotide interactions. Qualitative data are presented for inhibitory properties of the acyclonucleoside cyclic phosphates, and, in those instances where they were substrates, kinetic constants were evaluated. An unusual finding was the apparent ability of nuclease P1 to hydrolyse a five-membered cyclic phosphate ring of an acyclonucleoside.

Słowa kluczowe

EN

acyclonucleoside; substrate inhibitor; phosphate; enzyme system; cyclic phosphate

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1993
• Tom: 40
• Numer: 2
• Opis fizyczny: p.251-260,fig.

Twórcy

autor

Ciesla J. M.

• Polish Academy of Sciences, ul.Rakowiecka 36, 02-532 Warszawa, Poland

autor

Stolarski R.

autor

Shugar D.

Bibliografia

• 1. Elion, G.B., Furman, P.A., Fyfe,J.A., deMiranda, P., Beauchamp, L. & Schaeffer, H.J. (1977) Selectivity of action of an antiherpetic agent 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. U.S.A. 74,5716 - 5720.
• 2. De Clercq, E. (1984) Biochemical aspects of the selective antiherpes activity of nucleoside analogues. Biochem. Pharmacol..33,2159 - 2169.
• 3. Shugar, D. (1985) Antiviral agents - Some current developments. Pure Appl. Chem. 57,423 -440.
• 4. Furman, P.A., St. Clair, M.H. & Spector, T. (1984) Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase. J. Biol. Chem. 259,9575 - 9579.
• 5. Shugar, D. (1992) Phosphorylating enzymes involved in activation of chemotherapeutic nucleosides and nucleotides; in Molecular Aspects of Chemotherapy. Proceedings of the Third International Symposium, Gdansk, Poland, (Shugar, D., Rode, W. & Borowski, E., eds.) pp. 239 - 271. Springer Verlag, Berlin, Polish Scientific Publishers, PWN, Warszawa.
• 6. Oliver, S., Bubley, G. & Crumpacker, C. (1985) Inhibition of HSV-transformed murine cells by nucleoside analogues, 2'-NDG and 2'-nor- cGMP: mechanism of inhibition and reversal by exogenous nucleosides. Virology 145,84 - 95.
• 7. Tolman, R.L., Field, A.K., Karkas, J.D., Wagner, A.F., Germershausen, J., Crumpacker, C. & Scolnic, E.M. (1985) 2'-nor-cGMP: a seco-cyclic nucleotide with powerful anti-DNA viral activity. Biochem. Biophys. Res. Commun. 128, 1329 -1335.
• 8. Borghi, P., Di Marzio, P., Varano, B., Conti, L., Beraldelli, F. & Gessani, S. (1992) Cyclic AMP-mediated inhibition of vesicular stomatitis virus and herpes simplex virus replication in mouse macrophage-like cells. J. Gen. Virol. 73,2949 - 2954.9. Nokta, M.A. & Pollard, R.B. (1992) Immunodefi­ciency virus replication; Modulation by cellular levels of cAMP. Aids Res. & Human Retroviruses 8,1255 -1261.
• 10. Stolarski, R., Lassota, P., Kazimierczuk, Z. & Shugar, D. (1988) Solution conformation of some acyclo nucleoside and nucleotide analogues of antiviral acyclonucleosides, and their substrate/inhibitor properties in several enzyme systems, Z. Naturforsch. 43c, 231 - 242.
• 11. Stolarski, R., Cieśla, J.M. & Shugar, D. (1990) Monophosphates and cyclic phosphates of some antiviral acyclonucleosides: synthesis, conformation and substrate/inhibitor properties in some enzyme systems. Z. Naturforsch. 45c, 293 - 299.
• 12. Litter, E., Stuart, A.D. & Chee, M.S. (1992) Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature (London) 358,160 - 162.
• 13. Sullivan, V., Talarico, C.L., Stanat, S.C., Davis, M., Coen, D.M. & Biron, K.K. (1992) A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature (London) 358,162 -164.
• 14. Giziewicz, J. & Shugar, D. (1975) Preparative enzymie synthesis of nucleoside 5'-phosphates. Acta Biochim. Polon. 22,87 - 89.
• 15. Haasnoot, C.A.G., de Leeuw, F.A.A.M. & Altona, C. (1980) The relationship between proton-proton NMR coupling constants and substituent electronegativities I. An empirical generalization of the Karplus equation. Tetrahedron 36,2783 - 2792.
• 16. Lankhorst, P.L., Haasnoot, C.A.G., Erkelens, C. & Altona, C. (1984) Carbon-13 NMR in conformational analysis of nucleic acid fragments 2. A reparametrization of the Karplus equation for vicinal NMR coupling constants in COOP and HOOP fragments. J. Biomolec. Struct. Dyn. 1, 1387-1405.
• 17. Pearlman, D.A., Case, D.A., Caldwell, J., Seibel, G.L., Singh, U.C., Weiner, P.K. & Kollman, P.A. (1991) Amber 4.0 (UCSF), University of California, San Francisco.
• 18. Zan-Kowalczewska, M., Cieśla, J.M., Sierakowska, H. & Shugar, D. (1987) Potato tuber cyclic-nucleotide phosphodiesterase: selective inactivation of activity vs nucleoside cyclic 3',5'-phosphate and properties of the native and selective inactivated enzyme. Biochemistry 26,1194 - 1200.
• 19. Kamiński, Z.W. & Domino, E.F. (1987) Computer program for calculating of kinetic and pharmacologic parameters using a "direct linear plot derived algorithm. Computer Meth. Progr. Biomed. 24,41 - 45.
• 20. Altona, C. & Sundaralingam, M. (1972) Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. ]. Am. Chem. Soc. 94,8205 - 8212.
• 21. De Leeuw, H.P.M., Haasnoot, C.A.G. & Altona, C. (1980) Empirical correlations between conformational parameters in (3-D-furanoside fragments derived from a statistical survey of crystal structures of nucleic acid constituents. Israel J. Chem. 20,108 -126.
• 22. Stolarski, R., Kazimierczuk, Z., Lassota, P. & Shugar, D. (1986) Acyclo nucleosides and nucleotides: synthesis, conformation and other properties, and behaviour in some enzyme systems, of 2',3'-seco purine nucleosides, nucleotides and 3':5'-cyclic phosphates, analogues of cAMP and cGMP. Z. Naturforsch. 41c, 758 - 770.
• 23. Tolman, R.L. (1989) Structural requirements for enzymatic activation of acyclonucleotide analogues; in Nucleotide Analogues as Antiviral Agents (Martin, J.C., ed.) ACS Symp. Series No. 401, pp. 35-50.
• 24. Schaeffer, H.J., Gurwara, S., Vince, R. & Bittner, S. (1971) Novel substrate of adenosine deaminase. J. Med. Chem. 14,367 - 369.
• 25. Holy, A. & Ivanova, G.S. (1974) Aliphatic analogues of nucleotides: synthesis and affinity towards nucleases. Nucl. Acids Res. 1,19 - 34.
• 26. Miller, J.P., Shuman, D.A., Scholten, M.B., Dimmitt, M.K., Stewart, C.M., Khwaja, T.A., Robins, R.K. & Simon, L.N. (1973) Synthesis and biological activity of adenosine 3',5'-cyclic phosphate. Biochemistry 12,1010 -1016.
• 27. Miller, J.P, Boswell, K.H., Mian, A.M., Meyer, R.B., Jr, Robins, R.K. & Khwaja, T.A. (1976) 2'-Derivatives of guanosine and inosine cyclic 3',5'-phosphates. Synthesis, enzymic activity, and the effect of 8-substituents. Biochemistry 15, 217-223.
• 28. Potter, B.V.L., Connolly, B.A. & Eckstein, F. (1983) Synthesis and configurational analysis of dinucleoside phosphate isotopically chiral at phosphorus. Stereochemical course of Penicillium citrum nuclease Pi reaction. Biochemistry 22,1369 - 1377.
• 29. Uchida, T. & Egami, F. (1971) Microbial ribonucleases with special references to RNases Ti, T2, Ni, and U2; in The Enzymes (Boyer, P.D., ed.) vol. 4, pp. 205 - 220, Academic Press, New York & London.