Libraries discovery

E. A. An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries, discovery of a novel antagonist of E. coli dihydrofolate reductase. Int. J. Mass. Spectrom. 2004, 238, 77-83. 

Annis D.A., Athanasopoulos J., Curran P.J., Felsch J.S., Kalghatgi K., Lee W.H., Nash H.M., Orminati J.P.A., Rosner K.E., Shipps GW., Thaddupathy G.R.A., Tyler A.N., Vilenchik L., Wagner C.R., Wintner E.A., An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries. Discovery of a novel antagonist of E. coli dihydrofolate reductase Int. J. Mass Spectrom. 2004, 238, 77-83. 

Fowlkes, D. and McDonnell, D.P. (1999) Dissection of the LXXLL nuclear receptor— coactivator interaction motif using combinatorial peptide libraries discovery of peptide antagonists of estrogen receptors a and p. Molecular and Cellular Biology, 19, 8226-8239. 

Meseguer, B. et al., Sobd-phase synthesis and biological evaluation of a teleocidin library-discovery of a selective PKC8 down regulator, Chem. Eur. J., 6, 3943, 2000. 

R and M M Hann 2000. The In Silico World of Virtual Libraries. Drug Discovery Today 5 326-336. R and I D Kuntz 1990. Conformational Analysis of Flexible Ligands in Macromolecular eptor Sites. Journal of Computational Chemistry 13 730-748. 

E J, J M Blaney, M A Siani, D C Spellmeyer, A K Wong and W H Moos 1995. Measuring fersity Experimental Design of Combinatorial Libraries for Drug Discovery. Journal of dicinal Chemistry 38 1431-1436. 

MA Gallop, RW Baii et, WJ Dower, SPA Fodor, EM Gordon. Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J Med Chem 37 1233-1251, 1994. 

Experimental design of combinatorial libraries for drug discovery. J Med Chem 38(9) 1431-1436, 1995. 

A Polmski, RD Eemstem, S Shi, A Kuki. LiBrain Software for automated design of exploratory and targeted combinatorial libraries. In IM Chaiken, KD Janda, eds. Molecular Diversity and Combinatorial Chemistry Libraries and Drug Discovery. ACS Conf Proc Ser. Washington, DC Am Chem Soc, 1996, pp 219-232. 

Combinatorial chemistry has played an increasing role in drug discovery. Wacker et al. extended the Madelung indole process successfully to solid phase library synthesis for the preparation of 2,3-disubstituted indoles. A number of examples follow in the table. 

To speed the process of drug discovery, combinatorial chemistry> has been developed to prepare what are called combinatorial libraries, in which anywhere from a few dozen to several hundred thousand substances are prepared simultaneously. Among the early successes of combinatorial chemistry is the development of a benzodiazepine library, a class of aromatic compounds much used as antianxiety agents. 

Combinatorial chemistry, a new chapter of organic synthesis, is now developing rapidly. This new approach to synthesizing large designed or random chemical libraries through application of solid phase synthetic methods, promises to revolutionize the process of drug discovery in the pharmaceutical industry.24... 

The original library of 10 000 clones used in the Baeyer-Villiger reaction [89] was screened for performance as potential catalysts in the sulfoxidation [32]. This led to the discovery of at least 20 mutants having enantiomeric excess values in the range of 85-99%, some being (R) selective and others being (S) selective. Five mutants resulting in enantiomeric excess values of >95% were sequenced (Table 2.2) [32]. 

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