Identification of Enzyme Inhibitors from Phage-Displayed Combinatorial Peptide Libraries

Authors: Kay B.K.; Hamilton P.T.

Source: Combinatorial Chemistry & High Throughput Screening, Volume 4, Number 7, November 2001 , pp. 535-543(9)

Publisher: Bentham Science Publishers

Abstract:

In recent years, there have been a growing number of examples of the successful isolation of peptide ligands for enzymes from phage-displayed combinatorial peptide libraries. These peptides typically bind at or near the active site of the enzymes and can inhibit their activity. We review the literature on peptide ligands that have been isolated for enzymes other than proteases as well as present data on peptide ligands we have identified for E. coli dihydrofolate reductase (DHFR) which bind at, or near, the same site as the known inhibitors methotrexate or trimethoprim. Thus, while the peptide ligand isolated from phage-displayed libraries may not resemble the chemical structure of the normal substrate of the enzyme, the peptide can be used as an inhibitor to evaluate the function of the enzyme or for drug discovery efforts (i.e., as a lead compound for peptidomimetic design or as displaceable probe in high-throughput screens of libraries of small molecules).

Keywords: Enzyme inhibition; E. coli dihydrofolate reductase (DHFR); Protein phosphatase-1 (PP1); Dihydrofolate reductase (DHFR; Time-resolved Fluorescence (TRF); peptide ligands

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1386207013330760

Publication date: 2001-11-01

• Combinatorial Chemistry & High Throughput Screening publishes full length original research articles and reviews describing various topics in combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) and/or high throughput screening (e.g. developmental, practical or theoretical). Ancillary subjects of key importance, such as robotics and informatics, will also be covered by the journal. In these respective subject areas, Combinatorial Chemistry & High Throughput Screening is intended to function as the most comprehensive and up-to-date medium available. The journal should be of value to individuals engaged in the process of drug discoveryand development, in the settings of industry, academia or government.

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