Molecular recognition: The fragment approach in lead generation

Drug Discovery Today

Volumn 9, Issue 5, 2004, Pages 229-238

  Fattori, Daniela ^a  

^a Menarini Ricerche SpA   (Italy)

Author keywords

Chemical Biology; Drug Discovery; Fragment approach; Hydrophobic collapse; Lead generation; Molecular Medicine; Molecular recognition; Pharmaceutical Science

Indexed keywords

AQUEOUS SOLUTION; BINDING AFFINITY; BINDING SITE; CHEMICAL BOND; DRUG RESEARCH; EXPERIMENTATION; HYDROGEN BOND; MOLECULAR INTERACTION; MOLECULAR MECHANICS; MOLECULAR RECOGNITION; MOLECULAR SIZE; MOLECULE; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN TARGETING; REVIEW; STRUCTURE ANALYSIS;

CHEMISTRY, PHARMACEUTICAL; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 1242271305     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6446(03)03007-1     Document Type: Review

References (43)

1. Bohm H-J., Klebe G. What can we learn from molecular recognition in protein-ligands complexes for the design of new drugs? Angew. Chem., Int. Ed. Engl. 35:1996;2588-2614.
2. Connelly P.R., et al. Enthalpy of hydrogen bond formation in a protein-ligand binding reaction. Proc. Natl. Acad. Sci. U. S. A. 91:1994;1964-1968.
3. Klebe G., Boehm H.J. Energetic and entropic factors determining binding affinity in protein-ligand complexes. J. Recept. Signal Transduction Res. 17:1997;459-473.
4. Hunter C.A., et al. Aromatic interactions. J. Chem. Soc., Perkin Trans. 2:2001;651-669.
5. Jennings W.B., et al. Attractive intramolecular edge-to-face aromatic interactions in flexible organic molecules. Acc. Chem. Res. 34:2001;885-894.
6. Levitt M., Perutz M.F. Aromatic rings act as hydrogen bond acceptors. J. Mol. Biol. 201:1988;751-754.
7. Hunter, C.A. (1994) Meldola lecture. The role of aromatic interactions in molecular recognition. Chem. Soc. Rev. 101-109.
8. Teague S.J. Implications of protein flexibility for drug discovery. Nat. Rev. Drug Discov. 2:2003;527-541.
9. Stout T.J., et al. The additivity of substrate fragments in enzyme-ligand binding. Structure. 6:1998;839-848.
10. Gao J., et al. Increasing binding constants of ligands to carbonic anhydrase by using 'greasy tails'. J. Med. Chem. 38:1995;2292-2301.
11. Schneider H.J., et al. The incremental approach to non-covalent interactions: Coulomb and Van der Waals effect in organic ion pairs. J. Am. Chem. Soc. 114:1992;7698-7703.
12. Rishton G.M. Reactive compounds and in vitro false positives in HTS. Drug Discov. Today. 2:1997;382-384.
13. McGovern S.L., et al. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45:2002;1712-1722.
14. Roche O., et al. Development of a virtual screening method for identification of 'frequent hitters' in compounds libraries. J. Med. Chem. 45:2002;137-142.
15. Teague S.J., et al. The design of lead-like combinatorial libraries, Angew. Chem. Int. Ed. Engl. 38:1999;3743-3748.
16. Rishton G.M. Non lead-likeness and lead-likeness in biochemical screening. Drug Discov. Today. 8:2003;86-96.
17. Hann M.M., et al. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 41:2001;856-864.
18. Andrews P.R., et al. Functional group contributions to drug-receptor interactions. J. Med. Chem. 27:1984;1648-1657.
19. Rejito P.A., Verkhivker G.M. Unraveling principles of lead discovery: from unfrustrated energy landscapes to novel molecular anchors. Proc. Natl. Acad. Sci. U. S. A. 93:1996;8945-8950.
20. Rejito, P.A. and Verkhivker, G.M. (1998) Molecular anchors with large stability gaps ensure linear binding free energy relationships for hydrophobic substituents. Pac. Symp. Biocomput. 362-373.
21. Bemis J.W., Murcko M.A. The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 39:1996;2887-2893.
22. Comprehensive Medicinal Chemistry (CMC-3D) release 94.1, available from MDL Information Systems Inc., San Leandro, CA, USA.
23. Lewell X.Q., et al. 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. 38:1998;511-522.
24. Evans B.E., et al. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. J. Med. Chem. 31:1998;2235-2246.
25. Patchett A.A. 2002 Alfred Burger Award address in medicinal chemistry. Natural products and design: interrelated approaches in drug discovery. J. Med. Chem. 45:2002;5609-5616.
26. Patchett A.A., et al. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc. Natl. Acad. Sci. U. S. A. 92:1995;7001-7005.
27. Patchett A.A., et al. Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc. Natl. Acad. Sci. U. S. A. 95:1998;10836-10841.
28. Sebhat I.K., et al. Design and pharmacology of N-[(3R)-1,2,3,4- tetrahydroisoquinolinium-3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl) -2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J. Med. Chem. 45:2002;4589-4593.
29. Wiley R.A., Rich D.H. Peptidomimetic derived from natural products. Med. Res. Rev. 3:1993;327-384.
30. Patchett A.A., Nargund R.P. Privileged structures - an update. Annu. Rep. Med. Chem. 35:2000;289-297.
31. Babine R.E., Bender S.L. Molecular recognition of protein-ligand complexes: application to drug design. Chem. Rev. 97:1997;1359-1472.
32. Fabbro D., Garcia-Echeverria C. Targeting protein kinases in cancer therapy. Curr. Opin. Drug Discov. Devel. 5:2002;701-712.
33. Berg T. Modulation of protein-protein interactions with small organic molecules. Angew. Chem. Angew. Chem. Int. Ed. 42:2003;2462-2481.
34. Mueller G. Medicinal chemistry of target family-directed masterkeys. Drug Discov. Today. 8:2003;681-691.
35. McGovern S., et al. A specific mechanism of non specific inhibition. J. Med. Chem. 46:2003;4265-4272.
36. Hajduk P.J., et al. Privileged molecules for protein binding identified from NMR-based screening. J. Med. Chem. 43:2000;3443-3447.
37. Vetter D. Chemical microarrays, fragment diversity, label-free imaging by plasmon resonance - a chemical genomic approach. J. Cell. Biochem. Suppl. 39:2002;79-84.
38. Carr R., Jhoti H. Structure-based screening of low-affinity compounds. Drug Discov. Today. 7:2002;522-527.
39. Wyvratt M.J., Patchett A.A. Recent developments in the design of angiotensin-converting enzyme inhibitors. Med. Res. Rev. 5:1985;483-531.
40. Hartmann G.D., et al. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J. Med. Chem. 35:1992;4640-4642.
41. Freidinger R.M., Pettibone D.J. Small molecule ligands for oxytocin and vasopressin receptors. Med. Res. Rev. 17:1997;1-16.
42. Evans B.E., Bock M.G. Promiscuity in receptor ligand research: benzodiazepine-based cholecystokinin antagonists. Adv. Med. Chem. 2:1993;153-195.
43. Smith R.A., et al. Discovery of heterocyclic ureas as a new class of Raf Kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach. Bioorg. Med. Chem. Lett. 11:2001;2775-2778.