Targeting metalloenzymes: A strategy that works

Current Opinion in Pharmacology

Volumn 3, Issue 5, 2003, Pages 502-507

  White, Richard J ^a   Margolis, Peter S ^a   Trias, Joaquim ^a   Yuan, Zhengyu ^a  

^a Vicuron Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTINONIN; ANTIINFECTIVE AGENT; BACTERIAL ENZYME; BACTERIAL PROTEIN; BESTATIN DERIVATIVE; BETA LACTAM ANTIBIOTIC; BETA LACTAMASE INHIBITOR; CAPTOPRIL; CARBOXYLIC ACID DERIVATIVE; CHELATING AGENT; DIMERCAPROL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FOSMIDOMYCIN; HYDROLASE; HYDROXAMIC ACID; HYDROXYLAMINE; L 161 240; METALLOPROTEINASE; METALLOPROTEINASE INHIBITOR; METHIONYL AMINOPEPTIDASE; N [1 TERT BUTYL 2 OXO 2 [4 (2 THIAZOLYLMETHYL) 1 PIPERAZINYL]ETHYL] 3 CYCLOPENTYL 2 (N FORMYL N HYDROXYAMINOMETHYL)PROPIONAMIDE; N ACETYLGLUCOSAMINE; OXAZOLIDINONE DERIVATIVE; PEPTIDE DEFORMYLASE; PEPTIDE DEFORMYLASE INHIBITOR; SB 236049; UNCLASSIFIED DRUG; UNINDEXED DRUG; URIDINE DIPHOSPHATE N ACETYLGLUCOSAMINE; VRC 4887; VRC 5264;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; BACTERIAL GENOME; BACTERIAL INFECTION; CLINICAL TRIAL; DOSE RESPONSE; DRUG DESIGN; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG POTENTIATION; DRUG RESEARCH; DRUG TARGETING; ENZYME ANALYSIS; ENZYME CHEMISTRY; GENE LIBRARY; GENOMICS; HUMAN; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; PROBABILITY; PROCESS OPTIMIZATION; PROTEIN MOTIF; PROTEIN TARGETING; REVIEW; STRUCTURE ACTIVITY RELATION;

ALDOSE-KETOSE ISOMERASES; AMIDOHYDROLASES; ANTI-BACTERIAL AGENTS; BACTERIA; DRUG DESIGN; ENZYME INHIBITORS; ENZYMES; METALLOPROTEINS; MULTIENZYME COMPLEXES; OXIDOREDUCTASES;

EID: 0141535260     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1471-4892(03)00115-2     Document Type: Review

References (44)

1. Trias J. Gordon E.M. Innovative approaches to novel antibacterial drug discovery Curr. Opin. Biotechnol. 8 1997 757-762
2. Hutchison C.A. Peterson S.N. Gill S.R. Cline R.T. White O. Fraser C.M. Smith H.O. Venter J.C. Global transposon mutagenesis and a minimal mycoplasma genome Science 286 1999 2165-2169
3. Leung D. Abbenante G. Fairlie D.P. Protease inhibitors: current status and future prospects J. Med. Chem. 43 1999 305-341
4. Petrillo E.W. Jr. Ondetti M.A. Angiotensin-converting enzyme inhibitors: medicinal chemistry and biological actions Med. Res. Rev. 2 1982 1-41
5. Arigoni F. Talabot F. Peitsch M. Edgerton M.D. Meldrum E. Allet E. Fish R. Jamotte T. Curchod M.L. Loferer H. A genome-based approach for the identification of essential bacterial genes Nat. Biotechnol. 16 1998 851-856
6. Kobayashi K. Ehrlich S.D. Albertini A. Amati G. Andersen K.K. Arnaud M. Asai K. Ashikaga S. Aymerich S. Bessieres P. et al. Essential Bacillus subtilis genes Proc. Natl. Acad. Sci. USA 100 2003 4678-4683
7. BAD promoter J. Bacteriol. 177 1995 4121-4130
8. Waller A, Dudgenon T, Hars J, Johnson I, Czaplewski L, Hunter MG: A whole genome approach for validation of metalloenzyme targets to discover novel class antibiotics [abstract F2122]. 41th Annual ICAAC Meeting, Chicago, USA, 2001.Using 'signature' metalloenzyme motifs, the authors systematically searched for bacterial metalloenzymes that might be potential targets for antibacterial drug discovery.
9. Onishi H.R. Pelak B.A. Gerckens L.S. Silver L.L. Kahan F.M. Chen M.H. Patchett A.A. Galloway S.M. Hyland S.A. Anderson M.S. et al. Antibacterial agents that inhibit lipid A biosynthesis Science 274 1996 980-982
10. Yuan Z. Trias J. White R.J. Deformylase as a novel antibacterial target Drug Discov. Today 6 2001 954-961
11. Chen D.Z. Patel D.V. Hackbarth C.J. Wang W. Dreyer G. Young D.C. Margolis P.S. Wu C. Ni Z.J. Trias J. et al. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor Biochemistry 39 2000 1256-1262
12. Waller A.S. Clements J.M. Novel approaches to antimicrobial therapy: peptide deformylase Curr. Opin. Drug Discov. Dev. 5 2002 785-792
13. Clements J.M. Beckett R.P. Brown A. Catlin G. Lobell M. Palan S. Thomas W. Whittaker M. Wood S. Salama S. et al. Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor Antimicrob Agents Chemother 45 2001 563-570
14. Hackbarth C.J. Chen D.Z. Lewis J.G. Clark K. Mangold J.B. Cramer J.A. Margolis P.S. Wang W. Koehn J. Wu C. et al. N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity Antimicrob. Agents Chemother. 46 2002 2752-2764
15. Chen D, Wu C, Ni ZJ, Hackbarth CJ, Wang W, Patel DV, Trias J, White R, Yuan Z: Identification of alkyl-succinate-proline hydroxamates as peptide deformylase (PDF) inhibitors through integrated combinatorial and medicinal chemistry [abstract F1668]. 42th Annual ICAAC Meeting, San Diego, USA, 2002.
16. Margolis P.S. Hackbarth C.J. Young D.C. Wang W. Chen D. Yuan Z. White R. Trias J. Peptide deformylase in Staphylococcus aureus: resistance to inhibition is mediated by mutations in the formyltransferase gene Antimicrob. Agents Chemother. 44 2000 1825-1831
17. Margolis P. Hackbarth C. Lopez S. Maniar M. Wang W. Yuan Z. White R. Trias J. Resistance of Streptococcus pneumoniae to deformylase inhibitors is due to mutations in defB Antimicrob. Agents Chemother. 45 2001 2432-2435
18. Neckermann G, Fischer E, Pecanka R, Jain R, Sundaram S, Bracken K, Chen D, Dean K, Hackbarth C, Yuan Z: NVP-PDF386 (VRC4887), a new antibacterial peptide deformylase inhibitor: in vivo activities against S. aureus and S. pneumoniae infections in mice [abstract F1675]. 42th Annual ICAAC Meeting, San Diego, USA, 2002.
19. Azoulay-Dupuls E, Mohler J, Bedos JP, Moine P, Carbon C: Efficacy of BB-83698, a novel peptide deformylase inhibitor, against penicillin-susceptible and -resistant Streptococcus pneumoniae strains in a mouse pneumonia model [abstract F354]. 41th Annual ICAAC Meeting, Chicago, USA, 2001.
20. Wyckoff T.J. Lin S. Cotter R.J. Dotson G.D. Raetz C.R. Hydrocarbon rulers in UDP-N-acetylglucosamine acyltransferases J. Biol. Chem. 273 1998 32369-32372
21. Beall B. Lutkenhaus J. Sequence analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli J. Bacteriol. 169 1987 5408-5415
22. Akerley B.J. Rubin E.J. Novick V.L. Amaya K. Judson N. Mekalanos J.J. A genome-scale analysis for identification of genes required for growth or survival of Haemophilus influenzae Proc. Natl. Acad. Sci. USA 99 2002 966-971
23. Jackman J.E. Raetz C.R. Fierke C.A. Site-directed mutagenesis of the bacterial metalloamidase UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC). Identification of the zinc binding site Biochemistry 40 2001 514-523
24. McClure C.P. Rusche K.M. Peariso K. Jackman J.E. Fierke C.A. Penner-Hahn J.E. EXAFS studies of the zinc sites of UDP-(3-O-acyl )-N-acetylglucosamine deacetylase (LpxC) J. Inorg. Biochem. 94 2003 78-85
25. Wang W. Maniar M. Jain R. Jacobs J. Trias J. Yuan Z. A fluorescence-based homogeneous assay for measuring activity of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase Anal. Biochem. 290 2001 338-346
26. Pirrung M.C. Tumey L.N. Raetz C.R. Jackman J.E. Snehalatha K. McClerren A.L. Fierke C.A. Gantt S.L. Rusche K.M. Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal binding groups J. Med. Chem. 45 2002 4359-4370
27. Clements J.M. Coignard F. Johnson I. Chandler S. Palan S. Waller A. Wijkmans J. Hunter M.G. Antibacterial activities and characterization of novel inhibitors of LpxC Antimicrob. Agents Chemother. 46 2002 1793-1799
28. Gomez M, Hackbarth C, Rafanan N, Kubik B, Tembe V, Margolis P, Chen D, O'Dowd H, Raju B, et al.: VRC5264 a new inhibitor of LpxC, an essential gram-negative metalloenzyme [abstract F2034]. 42th Annual ICAAC Meeting, San Diego, USA, 2002.
29. Rohmer M. Knani M. Simonin P. Sutter B. Sahm H. Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate Biochem. J. 295 1993 517-524
30. Rohmer M. Isoprenoid biosynthesis via the mevalonate-independent route, a novel target for antibacterial drugs? Prog. Drug Res. 50 1998 135-154
31. Reuter K. Sanderbrand S. Jomaa H. Wiesner J. Steinbrecher I. Beck E. Hintz M. Klebe G. Stubbs M.T. Crystal structure of 1-deoxy-d-xylulose-5-phosphate reductoisomerase, a crucial enzyme in the non-mevalonate pathway of isoprenoid biosynthesis J. Biol. Chem. 277 2002 5378-5384
32. Yajima S. Nonaka T. Kuzuyama T. Seto H. Ohsawa K. Crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase complexed with cofactors: implications of a flexible loop movement upon substrate binding J. Biochem. (Tokyo) 131 2002 313-317
33. Kojo H. Shigi Y. Nishida M. FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability J. Antibiot. (Tokyo) 33 1980 44-48
34. Kuzuyama T. Shimizu T. Takahashi S. Seto H. Fosmidomycin, a specific inhibitor of 1-deoxy-d-xylulose-5 phosphate reductoisomerase in the nonmevalonate pathway for terpenoid biosynthesis Tetrahedron. Lett. 39 1998 7913-7916
35. Kuemmerle H.P. Murakawa T. Sakamoto H. Sato N. Konishi T. De Santis F. Fosmidomycin, a new phosphonic acid antibiotic. Part II: 1. Human pharmacokinetics. 2. Preliminary early phase IIa clinical studies Int. J. Clin. Pharmacol. Ther. Toxicol. 23 1985 521-528
36. Jomaa H. Wiesner J. Sanderbrand S. Altincicek B. Weidemeyer C. Hintz M. Turbachova I. Eberl M. Zeidler J. Lichtenthaler H.K. et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs Science 285 1999 1573-1576
37. Meinnel T. Mechulam Y. Blanquet S. Methionine as translation start signal: a review of the enzymes of the pathway in Escherichia coli Biochimie 75 1993 1061-1075
38. Vaughan M.D. Sampson P.B. Honek J.F. Methionine in and out of proteins: targets for drug design Curr. Med. Chem. 9 2002 385-409
39. Sandanayaka V.P. Prashad A.S. Resistance to beta-lactam antibiotics: structure and mechanism based design of beta-lactamase inhibitors Curr. Med. Chem. 9 2002 1145-1165
40. Payne D.J. Hueso-Rodriguez J.A. Boyd H. Concha N.O. Janson C.A. Gilpin M. Bateson J.H. Cheever C. Niconovich N.L. Pearson S. et al. Identification of a series of tricyclic natural products as potent broad-spectrum inhibitors of metallo-beta-lactamases Antimicrob. Agents Chemother. 46 2002 1880-1886
41. Reynolds P.E. Depardieu F. Dutka-Malen S. Arthur M. Courvalin P. Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of d-alanyl-d-alanine Mol. Microbiol. 13 1994 1065-1070
42. McCafferty D.G. Lessard I.A. Walsh C.T. Mutational analysis of potential zinc-binding residues in the active site of the enterococcal d-Ala-d-Ala dipeptidase VanX Biochemistry 36 1997 10498-10505
43. Lowther W.T. Orville A.M. Madden D.T. Lim S. Rich D.H. Matthews B.W. Escherichia coli methionine aminopeptidase: implications of crystallographic analyses of the native, mutant, and inhibited enzymes for the mechanism of catalysis Biochemistry 38 1999 7678-7688
44. Wu Z. Walsh C.T. Dithiol compounds: potent, time-dependent inhibitors of VanX, a zinc-dependent d,d-dipeptidase required for vancomycin resistance in Enterococcus faecium J. Am. Chem. Soc. 118 1996 1785-1786