Library targeted libraries

Key words High-throughput chemistry, chemical library, random library, targeted library, optimization library, library design, biological activity, drug discovery. 

Specific structural fragments of biologically active molecules can be used as the core elements for generating targeted libraries. The most straightfor-... 

Andrews KM, Cramer RD. Toward general methods of targeted library design topomer shape similarity searching with diverse structures as queries. / Med Chem 2000 43 1723-40. 

This chapter will cover recent developments in the design of diverse and protein family-targeted libraries, their physicochemical properties, and contemporary methods for screening them. 

Mena, M. A., Treynor, T. P., Mayo, S. L. and Daugherty, P. S. (2006). Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library. Nat. Biotechnol. 24, 1569-71. 

Keywords Combinatorial Chemistry m Solid-Phase Synthesis m Solid-Phase Scavenger m Linker m Targeted Library m Small Molecule Libraries... 

Targeted libraries have been most effective when based upon the display of diverse functionality about a minimal mechanism-based pharmacophore targeting an enzyme family. Early successes with this approach were first achieved with proteases.1221 Our own efforts to design libraries which target enzyme families require that the minimal pharmacophore serves as the site for attachment to solid support.1231 The pharmacophore is the only invariant part of the inhibitor structure, which... 

We have also developed targeted library approaches towards cysteine proteases, which are important pharmaceutical targets due to their role in the pathogenesis of many diseases.1251 A common feature of virtually all cysteine protease inhibitors is an electrophilic functionality, such as a carbonyl or a Michael acceptor, which can react with the nucleophilic active site cysteine residue. We specifi-... 

M. Whittaker, Discovery of Protease Inhibitors Using Targeted Libraries , Curr. Opin. Chem. Biol 1998, 2, 386-396. 

Targeted libraries are developed from knowledge of natural substrates or known inhibitors, which might venture to introduce some desirable physical properties [35]. 

Guo, T. and Hobbs, D.W. Privileged structure-based combinatorial libraries targeting G protein-coupled receptors. Assay Drug Dev. Tech. 2003, 1, 579-592. 

The statistics-based approach described consists of a series of automated procedures, is easily reproducible, and can be recommended for the practical design of compound libraries targeted against biotargets, for which sufficiently large number of selective ligands is available. It is important to note that all the procedures described are computationally inexpensive and permit real-time calculations with moderate hardware requirements. 

S. A., Okun, L, Ivashchenko, A.A., and Savchuk, N.P. Property-based design of GPCR-targeted library./. Chem. Inf. Comput. Sci. 2002, 42, 1332-1342. 

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