Applications of combinatorial libraries

Lam, K. S. 1997. Application of combinatorial library methods in cancer research and drug discovery. Anticancer Drug Des.,12,145-167. 

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. 

Mason JS, Morize 1, Menard PR, Cheney DL, Hulme C, Labaudiniere RF. New 4-point pharmacophore method for molecular similarity and diversity applications Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures. I Med Chem 1999 42 3251-64. 

Closely related to the use of PSA in virtual screening is its application in the design of combinatorial libraries with optimal properties. These applications are reviewed further in Refs. [46, 47], for example. 

The objective of traditional multistep synthesis is the preparation of a single pure compound, but combinatorial synthesis is designed to make many related molecules.57 The purpose is often to have a large collection (library) of compounds for evaluation of biological activity. A goal of combinatorial synthesis is structural diversity, that is, systematic variation in subunits and substituents so as to explore the effect of a range of structural entities. In this section, we consider examples of the application of combinatorial methods to several kinds of compounds. 

I High-Throughput Sample Preparation Techniques and Their Application to Bioanalytical Protocols and Purification of Combinatorial Libraries... 

Combinatorial approaches have been most successful when information about the target biomole cule has been considered in the design of the library. However, for many biomolecules, structural or mechanistic information is not available or does not provide sufficient insight to enable productive library design Also, lead compounds are not available for many targets, and in some cases, novel motifs for binding are desired. Under these circumstances, it is no surprise that the successful application of combinatorial chemistry has been less fre-... 

The Sulfoxide Glycosylation Method and its Application to Solid-Phase Oligosaccharide Synthesis and the Generation of Combinatorial Libraries... 

Gordon, E.M., Barrett, R.W., Dower, W.J., Fodor, P.A., and Gallop, M.A. Applications of combinatorial technologies to dmg discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. /. Med. Chem. 1994, 37, 1386-1401. 

Mason JS, Morize I, Menard PR, Cheney DL, Huhne C, Labaudiniere RF. (1999) New 4-Point Pharmacophore Method for Molecular Similarity and Diversity Appheations Overview of the Method and Applications, including a Novel Approach to the Design of Combinatorial Libraries Containing Privileged Substructures. J. Med. Chem. 42 3251-3264. 

The concepts of molecular similarity (1-3) and molecular diversity (4,5) play important roles in modern approaches to computer-aided molecular design. Molecular similarity provides the simplest, and most widely used, method for virtual screening and underlies the use of clustering methods on chemical databases. Molecular diversity analysis provides a range of tools for exploring the extent to which a set of molecules spans structural space, and underlies many approaches to compound selection and to the design of combinatorial libraries. Many different similarity and diversity methods have been described in the literature, and new methods continue to appear. This raises the question of how one can compare different methods, so as to identify the most appropriate method(s) for some particular application this chapter provides an overview of the ways in which this can be carried out, illustrating such comparisons by,... 

Yurek, D. A., Branch, D. L., and Kuo, M. S. (2002) Development of a system to evaluate compound identity, purity, and concentration in a single experiment and its application in quality assessment of combinatorial libraries and screening hits. 

ESI-MS has been used for the quantification of a number of substrates and products of enzymatic reactions [56,57]. Hsieh et al. report the use of ion spray mass spectrometry (a technical variation of electrospray ionization) coupled to HPLC for the kinetic analysis of enzymatic reactions in real time [58]. The hydrolysis of dinucleotides with bovine pancreatic ribonuclease A and the hydrolysis of lactose with 3-galactosidase were monitored and the resulting data were used for the estimation of and v x of these reactions. Another field of application of electrospray mass spectrometry is the screening of combinatorial libraries for potent inhibitors [31,59]. 

W. J., Cavallaro, C. L., Roughton, A. L., Zhao, W., Reader, J. C., Orlowski, M., Jacob-Samuel, B., Dilanni Carroll, C. (2000) A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophone molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis. J Comb Chem 2, 716-731. 

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