'Irreversible' slow-onset inhibition of orotate phosphoribosyltransferase by an amidrazone phosphate transition-state mimic

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 23, 2006, Pages 6112-6115

  Witte, John F ^a   Bray, Kathryn E ^a   Thornburg, Chelsea K ^a   McClard, Ronald W ^a  

^a REED COLLEGE   (United States)

Author keywords

Amidrazone; Oxocarbenium; Phosphoribosyltransferase; Slow onset inactivation; Transition state

Indexed keywords

AMIDRAZONE PHOSPHATE; ENZYME INHIBITOR; OROTATE PHOSPHORIBOSYLTRANSFERASE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME MECHANISM; ISOMERIZATION; NONHUMAN; PHASE TRANSITION;

ENZYME ACTIVATION; ENZYME INHIBITORS; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; OROTATE PHOSPHORIBOSYLTRANSFERASE; PYRIMIDINE NUCLEOTIDES; SACCHAROMYCES CEREVISIAE;

EID: 33750503589     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.08.109     Document Type: Article

References (31)

1. Schramm V.L., and Grubmeyer C. Prog. Nucleic Acid Res. Mol. Biol. 78 (2004) 261
2. Tao W., Grubmeyer C., and Blanchard J.S. Biochemistry 35 (1996) 14
3. Boutellier M., Horenstein B.A., Semenyaka A., Schramm V.L., and Ganem B. Biochemistry 33 (1994) 3994
4. Horenstein B.A., Zabinski R.F., and Schramm V.L. Tetrahedron Lett. 34 (1993) 7213
5. Horenstein B.A., and Schramm V.L. Biochemistry 32 (1993) 9917
6. Evans G.B., Furneaux R.H., Gainsford G.J., Schramm V.L., and Tyler P.C. Tetrahedron 56 (2000) 3053
7. Tong M.K., Papandreou G., and Ganem B. J. Am. Chem. Soc. 112 (1990) 6137
8. Ganem B., and Papandreou G. J. Am. Chem. Soc. 113 (1991) 8984
9. Tsujii E., Muroi M., Shiragami N., and Takatsuki A. Biochem. Biophys. Res. Commun. 220 (1996) 459
10. Witte J.F., and McClard R.W. Tetrahedron Lett. 32 (1991) 3927
11. Fleet W.J., and Son J.C. Tetrahedron 44 (1988) 2637 and references cited therein
12. Li C.M., Tyler P.C., Furneaux R.H., Kicska G., Xu Y., Grubmeyer C., Girvin M.E., and Schramm V.L. Nat. Struct. Biol. 6 (1999) 582
13. Shi W., Li C.M., Tyler P.C., Furneaux R.H., Grubmeyer C., Schramm V.L., and Almo S.C. Nat. Struct. Biol. 6 (1999) 588
14. Hurley, T. D. Personal communication.
15. Scapin G., Ozturk D.H., Grubmeyer C., and Sacchettini J.C. Biochemistry 33 (1994) 1287
16. McClard R.W., and Witte J.F. Bioorg. Chem. 18 (1990) 165
17. Witte J.F., and McClard R.W. Bioorg. Chem. 24 (1996) 29
18. Mitsunobu O., Kato K., and Kimura J. J. Am. Chem. Soc. 91 (1969) 6150
19. Detailed experimental procedures and chemical properties are provided in Supplementary information.
20. Witte J.F., Tsou R., and McClard R.W. Arch. Biochem. Biophys. 361 (1999) 106
21. 31P NMR over the course of the inactivation experiments.
22. McClard R.W., Holets E.A., MacKinnon A.L., and Witte J.F. Biochemistry 45 (2006) 5330
23. One referee correctly pointed out that the syntheses of compounds 10 and 12-14 involve common intermediates, which cannot therefore explain the observed inactivation of OPRTase as adventitious contaminants in 10. In addition, the one unique substance, 2-hydrazinobenzoate, when tested as a possible 2% contaminant at the highest concentration of 10 employed, produced no detectable inactivation of OPRTase over the course of eight days.
24. Umezu K., Amaya T., Yoshimoto A., and Tomita K. J. Biochem. 70 (1971) 249
25. 1.
26. Schloss J.V. Acc. Chem. Res. 21 (1988) 348
27. Schloss J.V. J. Biol. Chem. 263 (1988) 4145
28. Maurizi M.R., and Ginsburg A. J. Biol. Chem. 257 (1982) 4271
29. Morrison J.F., and Walsh C.T. Adv. Enzymol. Relat. Areas Mol. Biol. 61 (1998) 201
30. Smith J.L. Nat. Struct. Biol. 6 (1999) 502
31. Wang G.P., Cahill S.M., Liu X., Girvin M.E., and Grubmeyer C. Biochemistry 38 (1999) 284