Exhaustive de novo design of low-molecular-weight fragments against the ATP-binding site of DNA-gyrase

Journal of Chemical Information and Modeling

Volumn 46, Issue 3, 2006, Pages 1168-1173

  Firth Clark, Stuart ^a   Todorov, Nikolay P ^a   Alberts, Ian L ^a   Williams, Anthony ^a   James, Timothy ^a,b   Dean, Philip M ^a  

^a De Novo Pharmaceuticals Ltd   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINETRIPHOSPHATE; BINDING ENERGY; COMPUTATIONAL METHODS; STRUCTURE (COMPOSITION);

COMPUTATIONAL DRUG DESIGN; LEAD-LIKE STRUCTURES; SYNTHETIC TRACTABILITY;

MOLECULAR WEIGHT;

ADENOSINE TRIPHOSPHATE; DNA TOPOISOMERASE (ATP HYDROLYSING);

ARTICLE; BINDING SITE; DRUG DESIGN; METABOLISM; MOLECULAR WEIGHT;

ADENOSINE TRIPHOSPHATE; BINDING SITES; DNA GYRASE; DRUG DESIGN; MOLECULAR WEIGHT;

EID: 33745348671     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci050338i     Document Type: Article

References (29)

1. Erlanson, D. A.; McDowell, R. S.; O'Brien, T. Fragment-Based Drug Discovery. J. Med. Chem. 2004, 47, 3463-3482.
2. Hartshorn, M. J.; Murray, C. W.; Cleasby, A.; Frederickson, M.; Tickle, I. J.; Jhoti, H. Fragment-Based Lead Discovery Using X-ray Crystallography. J. Med. Chem. 2005, 48, 403-413.
3. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science 1996, 274, 1531-1534.
4. Hajduk, P. J.; Sheppard, G.; Nettesheim, D. G.; Olejniczak, E. T.; Shuker, S. B.; Meadows, R. P.; Steinman, D. H.; Carrera, G. M., Jr.; Marcotte, P. A.; Severin, J.; Walter, K.; Smith, H.; Gubbins, E.; Simmer, R.; Holzman, T. F.; Morgan, D. W.; Davidsen, S. K.; Summers, J. B.; Fesik, S. W. Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR. J. Am. Chem. Soc. 1997, 119, 5818-5827.
5. Hajduk, P. J.; Boyd, S.; Nettesheim, D.; Nienaber, V.; Severin, J.; Smith, R.; Davidson, D.; Rockway, T.; Fesik, S. W. Identification of Novel Inhibitors of Urokinase via NMR-Based Screening. J. Med. Chem. 2000, 43, 3862-3866.
6. Hajduk, P. J.; Gomtsyan, A.; Didomenico, S.; Cowart, M.; Bayburt, E. K.; Solomon, L.; Severin, J.; Smith, R.; Walter, K.; Holzman, T. F.; Stewart, A.; McGaraughty, S.; Jarvis, M. F.; Kowaluk, E. A.; Fesik, S. W. Design of Adenosine Kinase Inhibitors from the NMR-Based Screening of Fragments. J. Med. Chem. 2000, 43, 4781-4786.
7. Hajduk, P. J.; Shuker, S. B.; Nettesheim, D. G.; Craig, R.; Augeri, D. J.; Betebenner, D.; Albert, D. H.; Guo, Y.; Meadows, R. P.; Xu, L.; Michaelides, M.; Davidsen, S. K.; Fesik, S. W. NMR-Based Modification of Matrix Metalloproteinase Inhibitors with Improved Bioavailability. J. Med. Chem. 2002, 45, 5628-5639.
8. Deprez, P.; Mandine, E.; Gofflo, D.; Meunier, S.; Lesuisse, D. Small Ligands Interacting with the Phosphotyrosine Binding Pocket of the Src SH2 Protein. Bioorg. Med. Chem. Lett. 2002, 12, 1295-1298.
9. Lesuisse, D.; Lange, G.; Deprez, P.; Bénard, D.; School, B.; Delettre, G.; Marquette, J.-P.; Broto, P.; Jean-Baptiste, V.; Bichet, P.; Sarubbi, E.; Mandine, E. SAR and X-ray. A New Approach Combining Fragment-Based Screening and Rational Drug Design: Application to the Discovery of Nanomolar Inhibitors of Src SH2. J. Med. Chem. 2002, 45, 2379-2387.
10. Reece, R. J.; Maxwell, A. DNA Gyrase: Structure and Function. Crit. Rev. Biochem. Mol. Biol. 1991, 26, 335-375.
11. Boehm, H.-J.; Boehringer, M.; Bur, D.; Gmuender, H.; Huber, W.; Klaus, W.; Kostrewa, D.; Kuehne, H.; Luebbers, T.; Meunier-Keller, N.; Mueller, F. Novel Inhibitors of DNA Gyrase: 3D Structure Based Biased Needle Screening, Hit Validation by Biophysical Methods, and 3D Guided Optimization. A Promising Alternative to Random Screening. J. Med. Chem. 2000, 43, 2664-2674.
12. Lewell, X. Q.; Judd, D. B.; Watson, S. P.; Hann, M. M. RECAP-Retrosynthetic Combinatorial Analysis Procedure: A Powerful New Technique for Identifying Privileged Molecular Fragments with Useful Applications in Combinatorial Chemistry. J. Chem. Inf. Comput. Sci. 1998, 38, 511-522.
13. Bemis, G. W.; Murcko, M. A. The Properties of Known Drugs. 1. Molecular Frameworks. J. Med. Chem. 1996, 39, 2887-2893.
14. Bemis, G. W.; Murcko, M. A. Properties of Known Drugs. 2. Side Chains. J. Med. Chem. 1999, 42, 5095-5099.
15. Clark, M. Generalized Fragment-Substructure Based Property Prediction Method. J. Chem. Inf. Model. 2005, 45, 30-38.
16. Stahl, M.; Todorov, N. P.; James, T.; Mauser, H.; Boehm, H.-J.; Dean, P. M. A Validation Study on the Practical Use of Automated de novo Design. J. Comput.-Aided Mol. Des. 2002, 16, 459-478.
17. Todorov, N. P.; Dean, P. M. A Branch-and-Bound Method for Optimal Atom-Type Assignment in de novo Ligand Design. J. Comput.-Aided Mol. Des. 1998, 12, 335-349.
18. Todorov, N. P.; Dean, P. M. Evaluation of a Method for Controlling Molecular Scaffold Diversity in de novo Ligand Design. J. Comput.-Aided Mol. Des. 1997, 11, 175-192.
19. Kirkpatrick, S.; Gellatt, C. D., Jr.; Vecchi, M. P. Optimization by Simulated Annealing. Science 1983, 220, 671-680.
20. Brino, L.; Urzhumtsev, A.; Mousli, M.; Bronner, C.; Mitschler, A.; Oudet, P.; Moras, D. Dimerization of Escherichia coli DNA-gyrase B Provides a Structural Mechanism for Activating the ATPase Catalytic Center. J. Biol. Chem. 2000, 275, 9468-9475.
21. Garland, S. L. New Computational Methods for the Design of Peptidomimetics. Ph.D. Thesis, University of Cambridge, U.K., 1996.
22. Press, W. H.; Teukolsky, S. A.; Vetterling, W. T.; Flannery, B. P. Numerical Recipes, 2nd ed.; Cambridge University Press: 1992.
23. Stahl, M.; Rarey, M. Detailed Analysis of Scoring Functions for Virtual Screening. J. Med. Chem. 2001, 44, 1035-1042.
24. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand Efficiency: A Useful Metric for Lead Selection. Drug Discovery Today 2004, 9, 430-431.
25. Available Chemicals Directory is available from MDL Information Systems Inc., San Leandro, CA, 94577, and contains specialty bulk chemicals from commercial sources. Website: www.mdli.com.
26. Derwent World Drug Alerts, Derwent Information, London, 2002.
27. Xvmerlin a Daylight database system and SMARTMATCH a Daylight toolkit program, Daylight Chemical Information Systems Inc., http://www.daylight.com.
28. SMARTS is substructure chemical searching language used to query chemical structures as described in the following: James, C. A.; Weininger, D.; Delany, J. Daylight Theory Manual; Daylight Chemical Information Systems Inc., April 2005; http://www.daylight.com/dayhtml/doc/theory/theory.toc.html.
29. This procedure was automated using a modified version of the smiles2smarts tool kit program kindly provided by John Bradshaw, Daylight Chemical Information Systems.