Molecular recognition combinatorial libraries

H. P. Nestler and R. Liu, Combinatorial libraries studies in molecular recognition. Combinatorial Chemistry and High Throughput Screening, 1 (1998), 113—126. 

EMPl, selected by phage display from random peptide libraries, demonstrates that a dimer of a 20-residue peptide can mimic the function of a monomeric 166-residue protein. In contrast to the minimized Z domain, this selected peptide shares neither the sequence nor the structure of the natural hormone. Thus, there can be a number of ways to solve a molecular recognition problem, and combinatorial methods such as phage display allow us to sort through a multitude of structural scaffolds to discover novel solutions. 

Chemical templates are being increasingly employed for the development of dynamic combinatorial libraries (DCL) [94-98]. These (virtual) libraries of compounds are produced from all the possible combinations of a set of basic components that can reversibly react with each other with the consequent potential to generate a large pool of compounds. Because of the dynamic equilibria established in a DCL, the stabilization of any given compound by molecular recognition will amplify its formation. Hence the addition of a template to the library usually leads to the isolation of the compound that forms the thermodynamically more stable host-guest complex (see Scheme 37). 

PERMUTATIONS AND COMBINATIONS COMBINATORIAL LIBRARIES MOLECULAR RECOGNITION... 

Schneider-Mergener, J., Kramer, A., and Reineke, U. (1996) Peptide libraries bound to continuous cellulose membranes tools to study molecular recognition. In Combinatorial Libraries Synthesis, Screening and Application Potential, ed. R. Cortese. New York Walter de Gruyter. 

Over the past several years, combinatorial libraries of biological molecules, such as peptides and nucleic acids, have proven invaluable as reagents with which to study molecular recognition of proteins and non-proteins. Such libraries have been used extensively to define the specificity of protein/protein, protein/RNA, protein/peptide, and RNA/small molecule interactions. 

Combinatorial chemistry, in addition to facilitating the drug discovery process, is also an invaluable tool for basic research, particularly in the area of molecular recognition. Many biologically important molecular interactions involve proteins or peptides. Peptide libraries, therefore, will continue to be an extremely useful tool for basic research. 

Ludlow RF, Otto S (2010) The impact of the size of dynamic combinatorial libraries on the detectability of molecular recognition induced amplification. J Am Chem Soc 132 5984—5986... 

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