Macrocyclic inhibitors for peptide deformylase: A structure-activity relationship study of the ring size

Journal of Medicinal Chemistry

Volumn 47, Issue 20, 2004, Pages 4941-4949

  Hu, Xubo ^a   Nguyen, Kiet T ^a   Jiang, Vernon C ^b   Lofland, Denene ^b   Moser, Heinz E ^b   Pei, Dehua ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b Genesoft Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; HYDROXYLAMINE; MACROCYCLIC COMPOUND; METAL CHELATE; PEPTIDE DEFORMYLASE INHIBITOR;

ANTIBACTERIAL ACTIVITY; ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG BINDING SITE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; ENZYME BINDING; ENZYME INHIBITION; ENZYME STABILITY; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; IN VITRO STUDY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; RAT; STATISTICAL SIGNIFICANCE; STRUCTURE ACTIVITY RELATION;

AMIDOHYDROLASES; ANIMALS; ANTI-BACTERIAL AGENTS; BINDING SITES; DRUG EVALUATION, PRECLINICAL; DRUG STABILITY; ENZYME INHIBITORS; HETEROCYCLIC COMPOUNDS; HUMANS; MICROBIAL SENSITIVITY TESTS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 4544280990     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049592c     Document Type: Article

References (43)

1. Giglione, C.; Pierre, M.; Meinnel, T. Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents. Mol. Microbiol. 2000, 36, 1197-1205.
2. Pei, D. Peptide deformylase: A target for novel antibiotics? Emerging Ther. Targets 2001, 5, 23-40.
3. Yuan, Z.; Trias, J.; White, R. J. Deformylase as a novel antibacterial target. Drug Discovery Today 2001, 6, 954-961.
4. Clements, J. M.; Ayscough, A. P.; Keavey, K.; East, S. P. Peptide deformylase inhibitors, potential for a new class of broad spectrum antibacterials. Curr. Med. Chem. Anti-Infective Agents 2002, 1, 239-249.
5. Meinnel, T.; Mechulam, Y.; Blanquet, S. Methionine as translational start signal: A review of the enzymes of the pathway in Escherichia coli. Biochimie 1993, 75, 1061-1075.
6. Mazel, D.; Pochet, S.; Marliere, P. Genetic characterization of polypeptide deformylase, a distinctive enzyme of eubacterial translation. EMBO J. 1994, 13, 914-923.
7. Meinnel, T.; Blanquet, S. Characterization of the Thermus thermophilus locus encoding peptide deformylase and methionyl-tRNA(fMet) formyltransferase. J. Bacterial. 1994, 176, 7387-7390.
8. Margolis, P. S.; Hackbarth, C. J.; Young, D. C.; Wang, W.; Chen, D.; Yuan, Z.; White, R.; Trias, J. Peptide deformylase in S. aureus: Resistance to inhibition is mediated by mutations in the formyltransferase gene. Antimicrob. Agents Chemother. 2001, 44, 1825-1831.
9. Nguyen, K. T.; Hu, X.; Colton, C.; Chakratarti, R.; Zhu, M. X.; Pei, D. Characterization of a human peptide deformylase: Implications for antibacterial drug design. Biochemistry 2003, 42, 9952-9958.
10. Rajagopalan, P. T. R.; Yu, X. C.; Pei, D. Peptide deformylase: A new type of mononuclear iron protein. J. Am. Chem. Soc. 1997, 119, 12418-12419.
11. Groche, D.; Becker, A.; Schlichting, I.; Kabasch, W.; Schultz, S.; Wagner, A. F. V. Isolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site. Biochem. Biophys. Res. Commun. 1998, 246, 342-346.
12. Meinnel, T.; Patiny, L.; Ragusa, S.; Blanquet, S. Design and synthesis of substrate analogue inhibitors of peptide deformylase. Biochemistry 1999, 38, 4287-4295.
13. Huntington, K. M.; Yi, T.; Wei, Y.; Pei, D. Synthesis and antibacterial activity of peptide deformylase inhibitors. Biochemistry 2000, 39, 4543-4551.
14. Wei, Y.; Yi, T.; Huntington, K. M.; Chaudhury, C.; Pei, D. Identification of a potent peptide deformylase inhibitor from a rationally designed combinatorial library. J. Comb. Chem. 2000, 2, 650-657.
15. Chen, D. Z.; Patel, D. V.; Hackbarth, C. J.; Wang, W.; Dreyer, G.; Young, D.; Margolis, P. S.; Wu, C.; Ni, Z.-J.; Trias, J.; White, R.; Yuan, Z. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry 2000, 39, 1256-1262.
16. Apfel, C.; Banner, D. W.; Bur, D.; Dietz, M.; Hirata, T.; Hubschwerlen, C.; Locher, H.; Page, M. G. P.; Pirson, W.; Rosse, G.; Specklin, J.-L. Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. J. Med. Chem. 2000, 43, 2324-2331.
17. Jayasekera, M. M. K.; Kendall, A.; Shammas, R.; Dermyer, M.; Tomala, M.; Shapiro, M. A.; Holler, T. P. Novel nonpeptidic inhibitors of peptide deformylase. Arch. Biochem. Biophys. 2000, 381, 313-316.
18. Thorarensen, A.; Douglas, M. R., Jr.; Rohrer, D. C.; et al. Identification of novel potent hydroxamic acid inhibitors of peptidyl deformylase and the importance of the hydroxamic acid functionality on inhibition. Bioorg. Med. Chem. Lett. 2001, 11, 1355-1358.
19. Roblin, P. M.; Hammerschlag, M. R. In vitro activity of a new antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae. Antimicrob. Agents Chemother. 2003, 47, 1447-1448.
20. Coats, R. A.; Lee, S.-L.; Davis, K. A.; Patel, K. M.; Rhoads, E. K.; Howard, M. H. Stereochemical definition and chirospecific synthesis of the peptide deformylase inhibitor Sch 382583. J. Org. Chem. 2004, 69, 1734-1737.
21. Clements, J. M.; Beckett, R. P.; Brown, A.; Catlin, G.; Lobell, M.; Palan, S.; Thomas, W.; Wittaker, M.; Wood, S.; Salama, S.; Baker, P. J.; Rodgers, H. F.; Barynin, V.; Rice, D. W.; Hunter, M. G. Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor. Antimicrob. Agents Chemother. 2001, 45, 563-570.
22. Gross, M.; Clements, J.; Beckett, R. P.; Thomas, W.; Taylor, S.; Lofland, D.; Ramanathan-Girish, S.; Garcia, M.; Difuntorum, S.; Hoch, U.; Chen, H.; Johnson, K. W. Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide deformylase inhibitor. J. Antimicrob. Chemother. 2004, 53, 487-493.
23. Xue, C.-B.; He, X.; Roderick, J.; et al. Design and synthesis of cyclic inhibitors of matrix metalloproteases and TNF-α production. J. Med. Chem. 1998, 41, 1745-1748.
24. Wei, C.-Q.; Gao, Y.; Lee, K.; et al. Macrocyclization in the design of Grb2 SH2 domain-binding ligands exhibiting high potency in whole-cell systems. J. Med. Chem. 2003, 46, 244-254.
25. Hao, B.; Gong, W.; Rajagopalan, P. T. R.; Zhou, Y.; Pei, D.; Chan, M. K. Structural basis for the design of antibiotics targeting peptide deformylase. Biochemistry 1999, 38, 4712-4719.
26. Guilloteau, J.-P.; Mathieu, M.; Giglione, C.; Blanc, V.; Dupuy, A.; Chevrier, M.; Gil, P.; Famechon, A.; Meinnel, T.; Mikol, V. The crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types: A platform for the structure-based design of antibacterial agents. J. Mol. Biol. 2002, 320, 951-962.
27. Hu, X.; Nguyen, K. T.; Verlinde, C. L. M. J.; Hol, W. G. J.; Pei, D. Structure-based design of a macrocyclic inhibitor for peptide deformylase. J. Med. Chem. 2003, 46, 3771-3774.
28. Hu, Y. J.; Wei, Y.; Zhou, Y.; Rajagopalan, P. T. R.; Pei, D. Determination of substrate specificity for peptide deformylase through the screening of a combinatorial peptide library. Biochemistry 1999, 38, 643-650.
29. Ragusa, S.; Mouchet, P.; Lazennec, C.; Dive, V.; Meinnel, M. Substrate recognition and selectivity of peptide deformylase. Similarities and differences with metzincins and thermolysin. J. Mol. Biol. 1999, 289, 1445-1457.
30. Miller, S. J.; Blackwell, H. E.; Grubbs, R. H. Application of ringclosing metathesis to the synthesis of rigidified amino acids and peptides. J. Am. Chem. Soc. 1996, 118, 9606-9614.
31. Furstner, A. Olefin metathesis and beyond. Angew. Chem., Int. Ed. 2000, 39, 3012-3043.
32. Rajagopalan, P. T. R.; Datta, A.; Pei, D. Purification, characterization, and inhibition of peptide deformylase from Escherichia coli. Biochemistry 1997, 36, 13910-13918.
33. Lazennec, C.; Meinnel, T. Formate dehydrogenase-coupled spectrophotometric assay of peptide deformylase. Anal. Biochem. 1997, 244, 180-182.
34. Wei, Y.; Pei, D. Continuous spectrophotometric assay of peptide deformylase. Anal. Biochem. 1997, 250, 29-34.
35. Morrison, J. F.; Walsh, C. T. The behavior and significance of slow-binding enzyme inhibitors. Adv. Enzymol. 1988, 61, 201-301.
36. Nguyen, K. T.; Hu, X.; Pei, D. Slow-binding inhibition of peptide deformylase by cyclic peptidomimetics as revealed by a new spectrophotometric assay. Bioorg. Chem. 2004, 32, 178-191.
37. Wise, R.; Andrews, J. M.; Ashby, J. In vitro activities of peptide deformylase inhibitors against Gram-positive pathogens. Antimicrob. Agents Chemother. 2002, 46, 1117-1118.
38. Jones, R. N.; Rhomberg, P. R. Comparative spectrum and activity of NVP-PDF386 (VRC4887), a new peptide deformylase inhibitor. J. Antimicrob. Chemother. 2003, 51, 157-161.
39. Rajagopalan, P. T. R.; Grimme, S.; Pei, D. Characterization of cobalt(II)-substituted peptide deformylase: Function of the metal ion and the catalytic residue Glu-133. Biochemistry 2000, 39, 779-790.
40. McMartin, C.; Bohacek, R. J. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput.-Aided Mol. Des. 1997, 11, 333-344.
41. Osowska-Pacewicka, K.; Zwierzak, A. Two-carbon homologation of Grignard reagents to primary amines. Synthesis 1996, 3, 333-335.
42. Yebassa, D.; Balakrishnan, S.; Feresenbet, E.; Raghavan, D.; Start, P. R.; Hudson, S. D. Chemically functionalized clay vinyl ester nanocomposites: effect of processing parameters. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 1310-1321.
43. Fields, L. B.; Jacobsen, E. N. Synthesis and characterization of chiral bimetallic complexes bearing hard and soft Lewis acidic sites. Tetrahedron: Asymmetry 1993, 4, 2229-2240.