Time, life ... and mass spectrometry. New techniques to address biological questions

Within the last ten years, startling new developments in two ionization methods--matrix-assisted laser desorption (MALDI) and electrospray (ESI)--have been described by Karas et al. [M. Karas, D. Bachmann, U. Bahr, F. Hillenkamp, Int. J. Mass Spectrom. Ion Proc., 78 (1987) 53.] and by Fenn et al. [J.B. Fenn, M. Mann, C.K. Meng, S.F. Wong, C.M. Whitehouse, Science, 246 (1989) 64.], respectively. Their work demonstrated that these techniques, under appropriate experimental conditions, have high sensitivity and wide mass range, extending to hundreds of thousands of daltons and beyond, and thus can be extremely effective for the study of biopolymers. The result has been a revolution in the way that mass spectrometry experiments are carried out, a widening of the range of investigators who employ mass spectrometry in their own laboratories and a penetration of mass spectrometry into the investigation of biological phenomena that exceeds any previous expectations. Progress in improving mass spectral ionization and mass analysis methods and in interpreting and understanding the spectra is actively being pursued and exploited in many laboratories, to capitalize even further upon these advances. The results should facilitate understanding of structure-activity relationships pertinent to biology and medicine. In our laboratory, the focus of research is on oligosaccharide and glycoconjugate structural determinations, and on the improvement of methods for these important classes of compounds that relate to development, immune response, signalling, lipid and protein transport and disease. Representative examples of applications of MALDI and ESI mass spectrometry to these and other biological questions are provided herein.