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 ionization (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 process, however; means that ESI-MS is also finding application for the study of 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 the 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 binding affinities of drugs that bind to DNA via noncovalent interactions. Overall, the work in this area. to date has demonstrated that ESI-MS and MS/MS, will prove to be valuable complements to other structural methods, offering advantages in terms of speed, specificity, and sensitivity. (C) 2001 John Wiley & Sons, Inc.