Noncovalent complexes of nucleic acids and proteins studied by electrospray ionization mass spectrometry

The use of electrospray ionization-mass spectrometry (ESI-MS) for the characterization of noncovalent complexes of biomacromolecules from solution is based upon the gentle nature of the electrospray process. The important aspects of ESI source and interface conditions are described, with particular emphasis placed upon methods for distinguishing, and conditions for avoiding, artifacts due to gas phase complexes that may arise from nonspecific associations and aggregation due to ESI processes. Studies conducted under suitably gentle interface conditions and low concentrations are generally required, and it has now been shown that a wide range of specific interactions and associations in solution can be readily detected. Specific examples cited include tetrameric proteins (i.e., intact quaternary structure), oligonucleotide duplexes, duplex-drug complexes, and protein-inhibitor complexes. The potential for rapid affinity screening of combinatorial libraries and conducting competitive binding studies are suggested by recent results.