Use of structure-based drug design approaches to obtain novel anthranilic acid acyl carrier protein synthase inhibitors

Journal of Medicinal Chemistry

Volumn 48, Issue 25, 2005, Pages 7960-7969

  Joseph McCarthy, Diane ^a   Parris, Kevin ^a   Huang, Adrian ^a   Failli, Amedeo ^a   Quagliato, Dominick ^a   Dushin, Elizabeth Glasfeld ^b   Novikova, Elena ^b   Severina, Elena ^b   Tuckman, Margareta ^b   Petersen, Peter J ^b   Dean, Charles ^b   Fritz, Christian C ^c   Meshulam, Tova ^c   DeCenzo, Maureen ^c   Dick, Larry ^c   McFadyen, Iain J ^a   Somers, William S ^a   Lovering, Frank ^a   Gilbert, Adam M ^b  

^a PFIZER INC   (United States)

^b WYETH RESEARCH   (United States)

^c MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL CARRIER PROTEIN; ACYL CARRIER PROTEIN SYNTHASE INHIBITOR; COENZYME A; ENZYME INHIBITOR; PANTETHEINE PHOSPHATE; SERINE; UNCLASSIFIED DRUG;

ANTIBIOTIC SENSITIVITY; ARTICLE; CATALYSIS; CELL WALL; DRUG DESIGN; DRUG STRUCTURE; ENZYME ACTIVITY; HIGH THROUGHPUT SCREENING; LIGAND BINDING; STRUCTURE ANALYSIS;

ANTHRANILIC ACIDS; ANTI-BACTERIAL AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG RESISTANCE, BACTERIAL; GRAM-POSITIVE BACTERIA; LIGANDS; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; STEREOISOMERISM; TRANSFERASES (OTHER SUBSTITUTED PHOSPHATE GROUPS);

EID: 29144518553     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050523n     Document Type: Article

References (19)

1. Magnuson, K.; Jackowski, S.; Rock, C. O.; Cronan, J. E. J. Regulation of fatty acid biosynthesis in Escherichia coli. Microbiol. Rev. 1993, 57, 522-542.
2. Elovson, J.; Vagelos, P. R. Acyl carrier protein. X. Acyl carrier protein synthase. J. BM. Chem. 1968, 243, 3603-3611.
3. Parris, K. D.; Lin, L.; Tarn, A.; Mathew, R.; Hixon, J.; et al. Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites. Struct. Folding Des. 2000, 8, 883-895.
4. Chirgadze, N. Y.; Briggs, S. L.; McAllister, K. A.; Fischl, A. S.; Zhao, G. Crystal structure of Streptococcus pneumonias acyl carrier protein synthase: An essential enzyme in bacterial fatty acid biosynthesis. EMBO J. 2000, 19, 5281-5287.
5. Prescott, D. J.; Vagelos, P. R. Acyl Carrier Protein. Adv. Enzymol. 1971, 36, 269-311.
6. Takiff, H. E.; Baker, T.; Copeland, T.; Chen, S. M.; Court, D. L. Locating essential Escherichia coli genes by using mini-Tn 10 transposons: The pdxJ operon. J. Bacteriol. 1992, 174, 1544-1553.
7. McAllister, K. A.; Peery, R. B.; Meier, T. I.; Fischl, A. S.; Zhao, G. Biochemical and molecular analyses of the Streptococcus pneumoniae acyl carrier protein synthase, an enzyme essential for fatty acid biosynthesis. J. Biol. Chem. 2000, 275, 30864-30872.
8. Gilbert, A. M.; Kirisits, M.; Toy, P.; Nunn, D. S.; Failli, A.; et al. Anthranilate 4H-oxazol-5-ones: Novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 37-41.
9. Morbidoni, H. R.; de Mendoza, D.; Cronan, J. E., Jr. Bacillus subtilis acyl carrier protein is encoded in a cluster of lipid biosynthesis genes. J. Bacteriol. 1996, 178, 4794-4800.
10. Eliseev, A. V.; Lehn, J.-M. Dynamic combinatorial chemistry: Evolutionary formation and screening of molecular libraries. Curr. Top. Microbiol. Immunol. 1999, 243, 159-172.
11. Erlanson, D. A.; Braisted, A. C.; Raphael, D. R.; Randal, M.; Stroud, R. M.; et al. Site-directed ligand discovery. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 9367-9372.
12. Krawczyk, H.; Koszuk, J.; Bodalski, R. A Useful Synthesis of Diethyl 1-Substituted Vinylphosphonates. Pol. J. Chem. 2000, 74, 1123-1128.
13. Keating, D. H.; Carey, M. R.; Cronan, J. E., Jr. The unmodified (apo) form of Escherichia coli acyl carrier protein is a potent inhibitor of cell growth. J. Biol. Chem. 1995, 270, 22229-22235.
14. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standards, M7-A5; National Committee for Clinical Laboratory Standards: Wayne, PA, 2000.
15. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997, 276, 307-326.
16. Navaza, J. AmoRe: An automated package for molecular replacement. Acta Crystallogr., Sect. A: Found. Crystallogr. 1994, 40, 157-163.
17. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; et al. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 1983, 4, 187-217.
18. McMartin, C.; Bohacek, R. S. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput.-Aided Mol. Des. 1997, 11, 333-344.
19. Figures 5, 9, and the TOC graphic were created using the program PyMOL.; Delano, W. L. The PyMOL Molecular Graphics System; DeLano Scientific LLC: San Carlos, CA. http:// www.pymol.org.