Four decades of structure determination by mass spectrometry: From alkaloids to heparin

Abstract

The early (1950's and 1960's) use of mass spectrometry in natural products chemistry and its evolution to the present significance in biochemistry is recounted. This methodology allowed the facile and speedy determination of the structure of a number of indole alkaloids, such as sarpagine, quebrachamine, and two groups isolated from the roots of Aspidosperma quebracho blanco. At the same time, the first strategy for the sequencing of small peptides by mass spectrometry was demonstrated. It slowly advanced, over a period of two decades, to an important alternative of the ubiquitous automated Edman degradation. Further advances in methodology and instrumentation established mass spectrometry as today's indispensable tool for the characterization of proteins in biochemistry and biology. A new concept of the ionization of highly acidic compounds as the protonated complexes with basic peptides, which allows the accurate determination of the molecular weights of the former, a highly sensitive method for the sequencing of heparin fragments and related sulfated glycosaminoglycans was developed more recently. (J Am Soc Mass Spectrom 2002, 13, 1254-1272

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update covering the period 2001–2002

“…Many sulfated glycans are notoriously difficult to analyze and are prone to desulfation under MALDI conditions, a property that may explain why Araki et al (2002) did not observe any compounds other than the monomer in mixtures of a-amylase-derived oligomers from dextran sulfate, even though size-exclusion chromatography indicated the presence of oligomers with one to five residues. Ionpairing with basic peptides is a frequently used method for stabilizing these compounds for MALDI analysis (Biemann, 2002). Kreuger et al (2001) and several investigators (Kwan et al, 2001;Sturiale, Naggi, & Torri, 2001;Jemth et al, 2002;Guerrini et al, 2002) have used the method to study binding of fibroblast growth factors (FGF) to sulfated glycans.…”

Use of Associated Chromatographic Techniques in Bio-Monitored Isolation of Bioactive Monoterpenoid Indole Alkaloids from Aspidosperma ramiflorum

“…The major advantage of GC over the above-mentioned methods is its enhanced sensitivity and high resolution. Another advantage, it is easy coupling to a mass spectrometer (Biemann, 2002) that allows the identification of new and minor compounds of a mixture without laborious isolation procedures, which makes it a particularly attractive method when no decomposition due to the high temperatures applied in GC occurs but the widespread application of this technique is limited by volatility of more polar alkaloids.…”

Application of VUV synchrotron radiation to proteomic and analytical mass spectrometry

“…Tandem mass spectrometry consists in first selection of an ion of interest, followed by an activation step leading to an increase of the ion internal energy and ultimately to the fragmentation of the precursor. Proteins and poly-peptides fragment along a scheme, summarized in figure 1, which appears relatively simple regarding the chemical and structural complexity of these molecules [6]. The activation techniques of gas phase ions may be classified into two main groups.…”