I.
Introduction
370
II.
Techniques That Are Usually Employed in the Study of Bioorganic Macromolecules
371
A. Proteins and Peptides
371
B. Oligonucleotides
374
C. Oligosaccharides and Glycoconjugates
375
D. Various Complexes (DNA–Protein, Antigen–Antibody, Macromolecules–Metals)
377
III.
Common Problems and Developments in the Analysis of Bioorganic Macromolecules by Mass Spectrometry
377
A. Ionization Source Problems and Developments
377
1. Sensitivity
377
2. Problems with Buffers
379
3. Multicharge Effect
381
B. Mass Analyzer Problems and Developments
381
1. Linear Dynamic Range
381
2. Tandem Mass Spectrometry
382
3. Sensitivity
382
4. Resolution
383
5. Mass Accuracy
383
IV.
New Promising Technologies
384
A. Interfaces and Ionization Sources
384
1. Improvements in the Coupling of Liquid‐Phase Separation Systems to Mass Spectrometry
384
2. AP‐MALDI
384
3. Deprotonant Agents
385
4. Sonic Spray Ionization
388
5. APCI without Corona Discharge
391
B. Mass Analyzers
393
1. Linear Quadrupole Ion Trap
394
2. TOF Analyzers with New Detectors
395
3. Multiple Mass Analyzers
396
V.
Software for Data Treatment
397
VI.
Conclusions and Future Developments
399
Acknowledgments
400
References
400
In recent years, mass spectrometry has been increasingly used for the analysis of various macromolecules of biological, biomedical, and biochemical interest. This increase has been made possible by two key developments: the advent of electrospray ionization (ESI) and matrix‐assisted laser desorption ionization (MALDI) sources. The two new techniques produce a significant increase in mass range and in sensitivity that led to the development of new applications and of new analyzer designs, software, and robotics. This review, apart from the description of the status of mass spectrometry in the analysis of bioorganic macromolecules, is mainly devoted to the illustration of the more recent promising techniques and on their possible future evolution. © 2003
Wiley Periodicals, Inc., Mass Spec Rev 22:369–406, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mas.10062