Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles

Proceedings of the National Academy of Sciences of the United States of America

Volumn 107, Issue 44, 2010, Pages 18787-18792

  Clemons, Paul A ^a   Bodycombe, Nicole E ^a   Carrinski, Hyman A ^a   Wilson, J Anthony ^a   Shamji, Alykhan F ^a   Wagner, Bridget K ^a   Koehler, Angela N ^a   Schreiber, Stuart L ^a,b,c  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c HARVARD UNIVERSITY   (United States)

Author keywords

Chemical diversity; Cheminformatics; Natural products; Small molecule microarrays; Small molecule probes

Indexed keywords

ALPHA TOCOPHEROL; ANTINEOPLASTIC ALKALOID; COMPLEMENTARY DNA; METHYLTRANSFERASE; RECOMBINANT ENZYME; TOCOPHEROL C METHYLTRANSFERASE; UNCLASSIFIED DRUG; VINDOLINE;

ASPIDOSPERMA; CATALYSIS; CATHARANTHUS; CONFERENCE PAPER; DRUG SYNTHESIS; ENZYME SPECIFICITY; ESCHERICHIA COLI; GENE IDENTIFICATION; GENETIC CODE; GENETIC TRANSCRIPTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN METHYLATION; SEEDLING; SEQUENCE HOMOLOGY; STRUCTURAL HOMOLOGY;

EID: 78650459806     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1012741107     Document Type: Article

References (32)

1. Iwasa J, Fujita T, Hansch C (1965) Substituent constants for aliphatic functions obtained from partition coefficients. J Med Chem 8:150-153.
2. Fujita T, Hansch C (1967) Analysis of the structure-activity relationship of the sulfonamide drugs using substituent constants. J Med Chem 10:991-1000.
3. Feher M, Schmidt JM (2003) Property distributions: Differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43:218-227.
4. Ertl P, Schuffenhauer A (2008) Cheminformatics analysis of natural products: lessons from nature inspiring the design of new drugs. Prog Drug Res 66:218-235.
5. Singh N, et al. (2009) Chemoinformatic analysis of combinatorial libraries, drugs, natural products, and molecular libraries small molecule repository. J Chem Inf Model 49:1010-1024.
6. Lipinski CA (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliver Rev 23:3-25.
7. Lipinski CA, Hopkins A (2004) Navigating chemical space for biology and medicine. Nature 432:855-861.
8. Ganesan A (2008) The impact of natural products upon modern drug discovery. Curr Opin Chem Biol 12:306-317.
9. Schuffenhauer A, Brown N, Selzer P, Ertl P, Jacoby E (2006) Relationships between molecular complexity, biological activity, and structural diversity. J Chem Inf Model 46:525-535.
10. Muchmore SW, et al. (2008) Application of belief theory to similarity data fusion for use in analog searching and lead hopping. J Chem Inf Model 48:941-948.
11. Hann MM, Leach AR, Harper G (2001) Molecular complexity and its impact on the probability of finding leads for drug discovery. J Chem Inf Comput Sci 41:856-864.
12. Koehler AN, Shamji AF, Schreiber SL (2003) Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis. J Am Chem Soc 125:8420-8421.
13. Duffner JL, Clemons PA, Koehler AN (2007) A pipeline for ligand discovery using small-molecule microarrays. Curr Opin Chem Biol 11:74-82.
14. Lovering F, Bikker J, Humblet C (2009) Escape from flatland: Increasing saturation as an approach to improving clinical success. J Med Chem 52:6752-6756.
15. Bemis GW, Murcko MA (1996) The properties of known drugs. 1. Molecular frameworks. J Med Chem 39:2887-2893.
16. Lo MM, Neumann CS, Nagayama S, Perlstein EO, Schreiber SL (2004) A library of spirooxindoles based on a stereoselective three-component coupling reaction. J Am Chem Soc 126:16077-16086.
17. Massey FJ, Jr (1951) The Kolmogorov-Smirnov Test for Goodness of Fit. J Am Stat Assoc 46:68-78.
18. Rogers D, Brown RD, Hahn M (2005) Using extended-connectivity fingerprints with Laplacian-modified Bayesian analysis in high-throughput screening follow-up. J Biomol Screen 10:682-686.
19. Rogers D, Hahn M (2010) Extended-connectivity fingerprints. J Chem Inf Model 50:742-754.
20. Bradner JE, et al. (2006) A robust small-moleculemicroarray platform for screening cell lysates. Chem Biol 13:493-504.
21. Corey EJ, Cheng X-M (1989) The Logic of Chemical Synthesis (John Wiley, New York) p 436.
22. Sharpless KB (2002) Searching for new reactivity (Nobel lecture). Angew Chem Int Ed Engl 41(12):2024-2032.
23. Grubbs RH (2006) Olefin-metathesis catalysts for the preparation of molecules and materials (Nobel lecture). Angew Chem Int Ed Engl 45:3760-3765.
24. Beeler AB, Su S, Singleton CA, Porco JA, Jr (2007) Discovery of chemical reactions through multidimensional screening. J Am Chem Soc 129:1413-1419.
25. Muratore ME, et al. (2009) Enantioselective Bronsted acid-catalyzed N-acyliminium cyclization cascades. J Am Chem Soc 131:10796-10797.
26. Verendel JJ, et al. (2010) Highly flexible synthesis of chiral azacycles via iridiumcatalyzed hydrogenation. J Am Chem Soc 132:8880-8881.
27. Dancik V, Seiler KP, Young DW, Schreiber SL, Clemons PA (2010) Distinct biological network properties between the targets of natural products and disease genes. J Am Chem Soc 132:9259-9261.
28. Weininger DA (1988) SMILES, a chemical language and information system 1: Introduction and encoding rules. J Chem Inf Comput Sci 28:31-36.
29. Weininger DA, Weininger A, Weininger JL (1989) SMILES 2: Algorithm for generation of unique SMILES notation. J Chem Inf Comput Sci 29:97-101.
30. Seiler KP, et al. (2008) ChemBank: A small-molecule screening and cheminformatics resource database. Nucleic Acids Res 36:D351-359.
31. Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:65-70.
32. Sheshkin DJ (2004) Handbook of Parametric and Nonparametric Statistical Procedures (Chapman & Hall/CRC, Boca Raton, FL), 2nd Ed, p 1016