Combinatorial libraries enhanced

Combinatorial Library Enhanced by Recombination in Yeast (CLERY) similar diversity to family shuffling limited to protein screening in yeast Abecassis, 2000... 

CLERY (combinatorial libraries enhanced by recombination in yeast) 242... 

Tondi D, Costi MR Enhancing the drug discovery process by integration of structure-based design and combinatorial synthesis. In Viswanadhan AK, Chose VN, editors. Combinatorial library design and evaluation. New York Marcel Dekker, 2001. p. 563-604. 

Darvas F, Dorman G, Papp A. Diversity measures for enhancing ADME admissibility of combinatorial libraries. J Chem Inf Comput Sci 2000 40 314-22. Klopman G, Dimayuga M, Talafous J. META. 1. A program for the evaluation of metabolic transformations of chemicals. J Chem Inf Comput Sci 1994 34 1320-5. 

Nicolaou, K.C. Pfefferkom, J.A. Barluenga, S. Roecker, A.J. Cao, G.-Q. (2000C) Natural product-like combinatorial libraries based on privileged structures. 3. The libraries from libraries principle for diversity enhancement of benzopyran libraries. J. Am. Chem. Soc., 122, 968-76. 

The recent emergence of combinatorial libraries made up of millions of chemically diverse compounds has revolutionized the drug discovery process. In contrast to the expectations of rational drug design, which enables compounds to be designed based on a detailed understanding of molecular interactions, chemical library diversity allows both direct de novo discovery of lead compounds, as well as enhancement of the activity of existing compounds. Combinatorial chemistry has proven to be a... 

Figure 12.22 HPLC trace of a disulfide dynamic combinatorial library (a) with and (b) without addition of calmodulin. Dots indicate the peaks enhanced by the protein (Copyright Wiley VCH Verlag GmbH Co. KGaA. Reproduced by permission) (c) the chemical structure of the amplified ligand.

To test the new strains for enhanced permeability to small-molecular-weight inhibitors, SKY54 and SKY 197 and their parental strains were incubated with various concentrations of selected antifungal compounds, and with a diverse combinatorial library of uncharacterized compounds. 

When structure-based strategies are used to help choose reactants for a combinatorial library, the strengths of both approaches complement each other. Although the structure-based design is not accurate, it statistically enhances and focuses the combinatorial library. Billions of possible library compounds can be generated on the computer in a virtual library and evaluated. From this, a smaller set of the order of thousands can be chosen... 

Nefzi A, Ostresh JM, Yu Y, Maggiora GM, Medina-Franco JL, 46. Brunner D, Schneider J. Strategies for the use of mixture-based synthetic combinatorial libraries scaffold ranking, direct testing 47. in vivo, and enhanced deconvolution by computational methods. 

Initially, high-throughput characterization of combinatorial libraries was developed for and performed with single quadmpole instmments, providing unit-mass resolution and nominal molecular-mass determination. The application of high-resolution mass spectrometers, such as time-of-flight (TOF) and FT-ICR-MS, further enhances the power of the approach [22]. 

Darvas F, Dorman G, Papp A. Diversity measures for enhancing ADME admissibility of combinatorial libraries. J Chem Inf Comput Sci 2000 40 314-22. 

Finally, the bacterial PTE mentioned above has also been exhaustively studied with regard to its enantioselectivity. Initial studies used the known crystal structure of PTE to identify the substrate-binding pocket. This was then rationally evolved for enhancement and relaxation of the stereospecificity.97 Most recently, a combinatorial library has been screened for the resolution of chiral phosphate, phosphonate, and phosphinate esters.124 This work identified two variants with markedly different preferences for 5p- and Rp-enantiomers of 4-acetylphenyl methyl phenyl phosphate. One variant preferentially catalyzed hydrolysis of the 5p-enantiomer by a factor of 3.7 x 105, while the other preferentially catalyzed hydrolysis of the A p-enantiomer by a factor of 9.7 x 102 - an enantioselective discrimination of 3.6 x 108. 

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