Portal de Periódicos da CAPES

Applications of ESI-MS in drug discovery: interrogation of noncovalent complexes

2006; Nature Portfolio; Volume: 5; Issue: 7 Linguagem: Inglês

10.1038/nrd2083

1474-1784

Steven A. Hofstadler, Kristin A. Sannes‐Lowery,

Pesticide Residue Analysis and Safety

Mass spectrometry is emerging as a powerful analytical tool at various key stages in the drug discovery process. Hofstadler and Sannes-Lowery review the application of electrospray ionization mass spectrometry in the characterization of noncovalent complexes in drug discovery efforts against several classes of target. For many years, analytical mass spectrometry has had numerous supporting roles in the drug development process, including the assessment of compound purity; quantitation of absorption, distribution, metabolism and excretion; and compound-specific pharmacokinetic analyses. More recently, mass spectrometry has emerged as an effective technique for identifying lead compounds on the basis of the characterization of noncovalent ligand–macromolecular target interactions. This approach offers several attractive properties for screening applications in drug discovery compared with other strategies, including the small quantities of target and ligands required, and the capacity to study ligands or targets without having to label them. Here, we review the application of electrospray ionization mass spectrometry to the interrogation of noncovalent complexes, highlighting examples from drug discovery efforts aimed at a range of target classes.