MASS-SPECTROMETRIC INVESTIGATIONS OF DRUG-RECEPTOR INTERACTIONS

Mass spectrometric (MS) detection of biologically important noncovalent complexes is reviewed within the scope of on-going studies on this topic from this laboratory. The merits of ion spray MS and tandem MS are demonstrated in this area with examples that show systematic studies of several receptor-ligand, enzyme-substrate, and enzyme-product complexes associated with both an established well-characterized biological system (lysozyme hydrolysis of N-acetylglucosamine) and an important modern receptor-ligand complex (FKBP-FK-506 and FKBP-rapamycin). These examples and recent applications of negative ion MS and MS/MS with DNA adducts, heme-globin complexes, and antibiotic-binding proteins suggest an exciting new area of applications for MS that have not been previously available to investigators.