Development of new methodologies for the mass spectrometry study of bioorganic macromolecules

Abstract

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

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“…2) Table 1), albeit with low relative intensity (5-10% relative intensity), in which an ammonia ligand has been lost. These data match well with those from previous studies of cisplatin binding to single proteins [22,26,27]. All of the monoplatinated protein species are of approximately equal relative intensity (totalling around 10-20% relative intensity) with respect to the free protein signals, demonstrating that cisplatin reacts with each protein in the mixture to a similar extent.…”

“…However, the optimisation and the standardisation of experimental ESI MS procedures directed to metallodrugs require attention, since the variability in the ESI MS response depends on many factors, such as the nature of the protein, the nature of the metal/ligands/charge and the specific solution conditions (pH, buffer, etc.) [27,28].…”

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“…When combined with a multicapillary inlet, the interface provided more efficient introduction of ions, resulting in a significant enhancement in mass spectrometer sensitivity and detection limits. higher efficiency electrospray ionization/mass spectrometry (ESI-MS) interface has the potential to provide both increased sensitivity and lower detection limits, which in turn can decrease sample size requirements, increase analytical throughput, and enable new biological applications [1][2][3]. While ESI sensitivity can be increased by electrospraying at lower flow rates (i.e., nanoelectrospray [4]), this approach is ultimately limited by the flow rate at which ESI efficiency reaches 100% (generally in the low nL/ min regime) [2] and the fact that on-line separations (e.g., using liquid chromatography; LC) typically operate at much greater flow rates.…”

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