Nature's robots: A history of proteins: Tanford, C., Reynolds, J.

摘要

Nature's Robots: A History of Proteins Tanford, C., Reynolds, J.; Oxford University Press, 2001, 304 pp., ISBN 019-850-4667, $27.50. The authors justify their title, Nature's Robots, by noting that proteins and robots are both automatons that perform programmed functions. The objective of the authors is to inform contemporary protein scientists that their work rests on the shoulders of numerous predecessors; their book is designed to identify the pioneers (great and less great) and to define their achievements. The story begins in the mid-18th century when albumin, fibrin, and gelatin were recognized animal proteins, a century before the acceptance of the tetravalence of carbon championed by Kekulé. We learn that Jacob Berzelius (1779–1848), who was an organic chemist, and Gerrit Mulder (1802–1880), who practiced medicine and dabbled in chemistry, were responsible for the name protein, which means “standing in front.” %The book consists of four parts, “Chemistry” Chapters 1–9, “Detailed structure” Chapters 10–13, “Physiological function” Chapters 14–19, and “How are proteins made?” Chapters 20–22. By 1900 the notion that proteins are built up mainly from amino acids was accepted; a table provides the dates of the discoveries of the amino acids found in proteins beginning with leucine in 1819 and culminating with threonine in 1936. It is a remarkable coincidence that the nature of the peptide bond was announced at the same meeting on the same day in 1902 by Franz Hofmeister (in the morning) and Emil Fischer (in the afternoon). The authors refer to the announcement of the peptide bond as a watershed; on a single day the development of the entire field was changed. The authors describe the personalities and idiosyncrasies of many of the pioneers of protein science including Fischer. He obtained his Ph.D. under von Baeyer, “one of the most creative organic chemists of all time.” von Baeyer, in turn, studied with Kekulé. Fischer received the Nobel Prize for his work on carbohydrates in 1902. However, his work on proteins, peptides, and the peptide bond also represent distinguished contributions. He coined the terms “peptide” and “polypeptide.” Otto Warburg, one of the most influential biochemists of the 20th century, synthesized the first optically active peptides in Fischer's laboratory during the years 1903–1906. During his prime, Fischer commanded an institute of 250 people in Berlin. Fischer's work on the enzymatic degradation of glycosides led to his famous “lock-and-key” hypothesis. Fischer emulated Baeyer's penchant for working at the bench but suffered for it. Fischer developed mercury poisoning after inhaling gaseous diethylmercury. He also suffered from long term poisoning from phenylhydrazine (a key reagent in carbohydrate chemistry). Moreover, Fischer grieved the losses of two sons (who were killed in battle); he committed suicide in 1919. The nature of proteins as macromolecules or colloids was a debate that occupied scientists from 1920 to 1940. Colloid refers to an aggregate of lower molecular weight substances. Theodor Svedberg was an influential Swedish scientist who embraced initially the colloid hypothesis. Svedberg thought that the ultracentrifuge would reveal multiple boundaries from different components of “colloidal” hemoglobin. When the experiment was performed, however, a single moving boundary in a centrifugal field resulted; this outcome and Svedberg's conversion helped to turn the tide in favor of the macromolecule hypothesis. Other work showed that a single protein has multiple positive and negative charges; this result was a new and unexpected finding at the time. Arne Tiselius, a pioneer protein scientist who trained with Svedberg, separated complex protein mixtures by electrophoresis. The story of amino acid analyses begins with microbiological bioassays and progresses to the development of the ion-exchange column-based amino acid analyzer in the 1950s by William Stein and Stanford Moore at the Rocke