Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals, and proteins

Interactions of DNA with drugs, metal ions, and proteins are important in a wide variety of biological processes. With the advent of electrospray ioni zation (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry. (MS) is now a well-established tool for the characterization of the primary structures of biopolymers. The gentle nature of the ESI proc ess, however; means that ESI-MS is also finding application for the study o f noncovalent and other fragile biomolecular complexes. We outline here the progress, to date, in the use of ESI-MS for the study of noncovalent dnrg- DNA and protein-DNA complexes together with strategies that can be employed to examine the binding of small molecules and metal complexes to DNA. In t he case of covalent complexes with DNA, sequence information can be derived from ESI-MS used in conjunction with tandem mass spectrometry (MS/MS) and/ or enzymatic digestion. MS/MS can also be used to probe the relative bindin g affinities of drugs that bind to DNA via noncovalent interactions. Overal l, the work in this area. to date has demonstrated that ESI-MS and MS/MS, w ill prove to be valuable complements to other structural methods, offering advantages in terms of speed, specificity, and sensitivity. (C) 2001 John W iley & Sons, Inc.