Application of mass spectrometry for target identification and characterization

Mass spectrometry-based methodologies span the vast expanse of drug discove ry. Both electrospray ionization (ESI) and matrix-assisted laser desorption /ionization (MALDI) support proteomics-based research projects by identifyi ng proteins separated and isolated by polyacrylamide gel electrophoresis. M ALDI-MS-based surface scanning of one-dimensional isoelectric focusing gels , "virtual 2-D gel electrophoresis," represents a potentially high throughp ut means to map proteins and to determine protein profiles. Mass spectromet ry can also be used to directly study the covalent and noncovalent interact ions of drug molecules and biomolecule targets. Drug binding examples discu ssed include the binding of covalent and noncovalent inhibitors to are SH2 domain protein, and the interaction of aminoglycosicde antibiotic neomycin and HIV Tat peptide-TAR RNA. (C) 1999 John Wiley & Sons, Inc.