Discovery of enzyme inhibitors through combinatorial chemistry

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...

Full description

Saved in:
Bibliographic Details
Published in:Molecular diversity 1997-04, Vol.2 (4), p.223-236
Main Author: Dolle, R E
Format: Article
Language:English
Subjects:
Biotechnology - methods
Drug Design
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Enzymes
Libraries
Protease Inhibitors - chemistry
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1381-1991
1573-501X
DOI:10.1007/bf01715638