Second-generation dimeric inhibitors of chitin synthase

Bioorganic and Medicinal Chemistry

Volumn 12, Issue 24, 2004, Pages 6451-6460

  Yeager, Adam R ^a   Finney, Nathaniel S ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Glycosyltransferase; Inhibitor; Mechanism; Phosphate mimic

Indexed keywords

ANTIFUNGAL AGENT; CHITIN SYNTHASE INHIBITOR; ENZYME INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG DESIGN; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME MECHANISM; IC 50; REACTION ANALYSIS;

ANTIFUNGAL AGENTS; CHITIN SYNTHASE; CROSS-LINKING REAGENTS; DIMERIZATION; ENZYME INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; TARTRATES; URIDINE;

EID: 8844244631     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2004.09.027     Document Type: Article

References (41)

1. For representative overviews of fungal chitin synthase (EC 2.4.1.16): C.A. Munro, and N.A.R. Gow Med. Mycol. 39 2001 41 53
2. M.H. Valdivieso, A. Duran, and C. Roncero EXS 87 1999 55 69
3. R.A. Merz, M. Horsch, L.E. Nyhlen, and D.M. Rast EXS 87 1999 9 37
4. E. Cabib Adv. Enzymol. 59 1987 59 101
5. Glycosyltransferase structural determination is a growing field, as demonstrated by the following reports: N.C. Strynadka, G. Withers Stephen, and W.W. Wakarchuk Nat. Struct. Biol. 11 2004 163 170
6. G.J. Davies Nat. Struct. Biol. 8 2001 98 100
7. S.J. Charnock, B. Henrissat, and G.J. Davies Plant Physiol. 125 2001 527 531 However, to date no structures of polymerizing transferases have been determined
8. D. Zhang, and M.J. Miller Curr. Pharm. Des. 5 1999 73 99
9. J. Grugier, J. Xie, I. Duarte, and J.-M. Valery J. Org. Chem. 65 2000 979 984
10. A. Schafer, and J. Thiem J. Org. Chem. 65 2000 24 29
11. J. Xie, A. Thellend, H. Becker, and A. Vidal-Cros Carbohydr. Res. 334 2001 177 182
12. K. Obi, J.-I. Uda, K. Iwase, O. Sugimoto, H. Ebisu, and A. Matsuda Bioorg. Med. Chem. Lett. 10 2000 1451 1454
13. J.-B. Behr, I. Gautier-Lefebvre, C. Mvondo-Evina, G. Guillerm, and N.S. Ryder J. Enzym. Inhib. 16 2001 107 112
14. R. Wang, D.H. Steensma, Y. Takaoka, J.W. Yun, T. Kajimoto, and C.-H. Wong Bioorg. Med. Chem. 5 1997 661 672
15. Yeager, A. R.; Finney, N. S. In Abstract of Papers, 221st ORGN-102, American Chemical Society, 2001, San Diego, CA, 2002
16. R. Chang, A.R. Yeager, and N.S. Finney Org. Biomol. Chem. 1 2003 39 41
17. A.R. Yeager, and N.S. Finney J. Org. Chem. 69 2004 613 618
18. For previous discussion of possible mechanisms for CS and/or other polymerizing transferases, see: I.M. Saxena, R.M. Brown Jr., M. Fevre, R.A. Geremia, and B. Henrissat J. Bacteriol. 177 1995 1419 1424
19. I.M. Saxena, R.M. Brown Jr., and T. Dandekar Phytochemistry 57 2001 1135 1148
20. I.M. Saxena, and R.M. Brown Jr. Curr. Opin. Plant Biol. 3 2000 523 531
21. E. Kamst, and P.H. Spaink Trends Glycosci. Glycotechnol. 11 1999 187 199 See also Refs. b and c
22. The peptidyl nucleoside compounds have multiple key functional groups that increase binding ability, overcoming the generally weak interaction of the native substrate. See Ref. 3 and the following representative examples: K. Isono, T. Azuma, and S. Suzuki Chem. Pharm. Bull. 19 1971 505 512
23. E. Krainer, J.M. Becker, and F. Naider J. Med. Chem. 34 1991 174 180
24. F. Naider, P. Shenbagamurthi, A.S. Steinfeld, H.A. Smith, C. Boney, and J.M. Becker Antimicrob. Agents Chemother. 24 1983 787 796
25. R.K. Khare, J.M. Becker, and F. Naider J. Med. Chem. 31 1988 650 656
26. For recent examples of synthetic studies on the polyoxins and related compounds, see: A. Dondoni, S. Franco, F. Junquera, F.L. Merchan, P. Merino, and T. Tejero J. Org. Chem. 62 1998 5497 5507
27. J.D. More, and N.S. Finney Synlett 9 2003 1307 1310
28. Previous studies of the use of the tartrate moiety as a diphosphate have provided mixed results. See Ref. 4 and J.-B. Behr, T. Gourlain, A. Helimi, and G. Guillerm Bioorg. Med. Chem. Lett. 13 2003 1713 1716
29. For a convenient preparation of 15, see Ref. b
30. Imide carbonate protection was necessary to prevent unwanted acylation of the uracil ring during amide bond formation
31. J.A. Musich, and H. Rapoport J. Am. Chem. Soc. 100 1978 4865 4872
32. B.F. Lundt, N.L. Johansen, A. Volund, and J. Markussen Int. J. Pept. Protein Res. 12 1978 258 268
33. The less expensive R,R-tartrate was chosen for dimerization, as the R,R- and S,S-amides provided inhibition within experimental error of one another
34. V. Dourtoglou, J.C. Ziegler, and B. Gross Tetrahedron Lett. 19 1978 1269 1272
35. R. Knorr, A. Trzeciak, W. Bannwarth, and D. Gillessen Tetrahedron Lett. 30 1989 1927 1930
36. 1H NMR after chromatography on silica, further purification on reverse-phase silica was essential for obtaining reproducible assay results
37. Maximum 5′-5′ distances were calculated using Chem3D 3.0 (Cambridgesoft, Cambridge, MA). The maximum distance was determined after manually adjusting dihedral angles to attain the most extended conformation possible
38. A.V. Finkelstein, and J. Janin Protein Eng. 3 1989 1 3
39. M.S. Searle, and D.H. Williams J. Am. Chem. Soc. 114 1992 10690 10697
40. M.S. Searle, D.H. Williams, and U. Gerhard J. Am. Chem. Soc. 114 1992 10697 10704
41. P. Orlean J. Biol. Chem. 262 1987 5732 5739