Target identification of covalently binding drugs by activity-based protein profiling (ABPP)

Christian M Pichler; Joanna Krysiak; Rolf Breinbauer

doi:10.1016/j.bmc.2016.03.050

Target identification of covalently binding drugs by activity-based protein profiling (ABPP)

Bioorg Med Chem. 2016 Aug 1;24(15):3291-303. doi: 10.1016/j.bmc.2016.03.050. Epub 2016 Mar 30.

Authors

Christian M Pichler¹, Joanna Krysiak², Rolf Breinbauer³

Affiliations

¹ Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria.
² Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
³ Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria. Electronic address: [email protected].

PMID: 27085673
DOI: 10.1016/j.bmc.2016.03.050

Abstract

The characterization of the target proteins of drug molecules has become an important goal in understanding its mode of action and origin of side effects due to off-target binding. This is especially important for covalently binding drugs usually containing electrophilic moieties, which potentially can react with nucleophilic residues found in many proteins. This review gives a comprehensive overview of the use of activity-based protein profiling (ABPP) as an efficient tool for the target identification of covalently binding drugs.

Keywords: Activity based protein profiling; Biologically active molecules; Covalent binding drugs; Drug targets; Target identification.

Publication types

Review

MeSH terms

Animals
Drug Discovery / methods*
Humans
Molecular Targeted Therapy / methods*
Pharmaceutical Preparations / chemistry*
Pharmaceutical Preparations / metabolism*
Protein Binding
Proteins / chemistry*
Proteins / metabolism*

Substances

Pharmaceutical Preparations
Proteins