Structure Determination of Natural Products by Mass Spectrometry.

I review laboratory research on the development of mass spectrometric methodology for the determination of the structure of natural products of biological and medical interest, which I conducted from 1958 to the end of the twentieth century. The methodology was developed by converting small peptides to their corresponding polyamino alcohols to make them amenable to mass spectrometry, thereby making it applicable to whole proteins. The structures of alkaloids were determined by analyzing the fragmentation of a known alkaloid and then using the results to deduce the structures of related compounds. Heparin-like structures were investigated by determining their molecular weights from the mass of protonated molecular ions of complexes with highly basic, synthetic peptides. Mass spectrometry was also employed in the analysis of lunar material returned by the Apollo missions. A miniaturized gas chromatograph mass spectrometer was sent to Mars on board of the two Viking 1976 spacecrafts.

Laying the groundwork for proteomics: mass spectrometry from 1958 to 1988.

The development of mass spectrometric methods in peptide and protein chemistry in the author's laboratory is reviewed, from the first determination of the amino acid sequence of small peptides in the late 1950s to its use for the determination of the primary structure of large proteins by a combination of mass spectrometry and DNA sequencing in the late 1980s. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

On the ability of the Viking gas chromatograph-mass spectrometer to detect organic matter.

A recent paper by Navarro-Gonzalez et al. [Navarro-Gonzalez R, Navarro KF, de la Rosa J, Iniguez E, Molina P, Miranda LD, Morales P, Cienfuegos E, Coll P, Raulin F, et al. (2006) Proc Natl Acad Sci USA 103:16089-16094] claims to show that the Viking GCMS (gas chromatograph-mass spectrometer) experiment, which carried out a search for organic matter at the surface of Mars in 1976, "may have been blind to low levels of organics." To rebut this assertion, the Viking experiment, test data, and results on Mars are reviewed, and the fallacies in the design, execution, and interpretation of the new experiments presented by Navarro-Gonzalez et al. are critically examined.

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

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.