Discovery of enzyme inhibitors through combinatorial chemistry
- 1 April 1997
- journal article
- review article
- Published by Springer Nature in Molecular Diversity
- Vol. 2 (4) , 223-236
- https://doi.org/10.1007/bf01715638
Abstract
This review serves to highlight the recent examples of combinatoric methodology as applied to the discovery and optimization of enzyme inhibitors. Early research efforts focused on the identification of polypeptides from libraries as inhibitors of proteases. As solution- and solid-phase chemistries gain in sophistication, libraries containing less peptidic structural motifs have been created. A recurring design stratagem relies on the synthesis of libraries incorporating pharmacophores with known affinity for the target enzyme. Screening of these structure-based libraries has led to the discovery of small-molecule inhibitors of both proteolytic and non-proteolytic enzymes alike. Two tables are provided listing the enzyme targeted libraries through 1996. A name, generic structure and size is given for each library citation, accompanied by the enzyme screen and the structure and potency of the most active library member.Keywords
This publication has 32 references indexed in Scilit:
- Rapid synthesis of novel dipeptide inhibitors of human collagenase and gelatinase using solid phase chemistryBioorganic & Medicinal Chemistry Letters, 1996
- Development of the First Potent and Selective Inhibitor of the Zinc Endopeptidase Neurolysin Using a Systematic Approach Based on Combinatorial Chemistry of Phosphinic PeptidesJournal of Biological Chemistry, 1996
- Solid phase synthesis of phosphinic acid endothelin converting enzyme inhibitorsBioorganic & Medicinal Chemistry Letters, 1996
- Strategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug DiscoveryAccounts of Chemical Research, 1996
- Design, Synthesis, and Evaluation of Small-Molecule LibrariesAccounts of Chemical Research, 1996
- The identification of cyclooxygenase-1 inhibitors from 4-thiazolidinone combinatorial librariesBioorganic & Medicinal Chemistry Letters, 1996
- Multiple simultaneous synthesis of phenolic librariesMolecular Diversity, 1995
- Solid Phase Synthesis of Lavendustin A and AnalogsThe Journal of Organic Chemistry, 1995
- Synthesis of a Small Molecule Combinatorial Library Encoded with Molecular TagsJournal of the American Chemical Society, 1995
- A Transition State Analog Inhibitor Combinatorial LibraryJournal of the American Chemical Society, 1995