Abstract

The initial stages of drug discovery are increasingly reliant on development and improvement of analytical methods to investigate protein-protein and protein-ligand interactions. For over 20 years, mass spectrometry (MS) has been recognized as providing a fast, sensitive and high-throughput methodology for analysis of weak non-covalent complexes. Careful control of electrospray ionization conditions has enabled investigation of the structure, stability and interactions of proteins and peptides in a solvent free environment. This critical review covers the use of mass spectrometry for kinetic, dynamic and structural studies of proteins and protein complexes. We discuss how conjunction of mass spectrometry with related techniques and methodologies such as ion mobility, hydrogen-deuterium exchange (HDX), protein footprinting or chemical cross-linking can provide us with structural information useful for drug development. Along with other biophysical techniques, such as NMR or X-ray crystallography, mass spectrometry provides a powerful toolbox for investigation of biological problems of medical relevance (204 references).

Links

Publisher Full Text

Authors

Pacholarz KJ, Garlish RA, Taylor RJ, Barran PE

Institution

School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.

Source

Chemical Society reviews 41:11 2012 Jun 7 pg 4335-55

MeSH

Deuterium Exchange Measurement
Drug Discovery
Ligands
Mass Spectrometry
Peptide Mapping
Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22532017