A Brief History of Polypeptide Chemistry

Protein chcmistry really began in the 1830s with Mulder's systematic investigation of nitrogenous biological materials, such as blood fibrin, egg white, gelatins, and silk. In 1840, Huncfeld was the first to crystallize a protein—viz., hemoglobin. During the following 90 years, amino acids, the building blocks of protein, were isolated by many investigators, but for many years it was not realized how amino acids were linked to form proteins. In fact, it was not until 1902 that Fisher and Hofmcistcr independently proposed that amino acids were joined together by peptide bonds (—CO—NH—).

It was not the early work on protein chcmistry, however, that led to the conccpt of enzymes as catalysts of biological reactions. Indeed, it was the early research on fermentation of Lavoisier in the later 1700s and the subsequent work by Schwann, Pasteur, and Buchncr between 1830 and 1900 that led to the development of this conccpt. Oncc the role of enzymes was realized, scientists, uncluding Harden and Young, Embodcn and Meycrhof, Krcbs, Lyncn and Lipmann, were eventually able to formulate the individual steps of most of the metabolic processes in the body.


In 1926, Sumner made a tremendous advance when he recognized that enzymes were, in fact, proteins. He camc to this conclusion after he had successfully crystallized a protein that was associated with enzymatic activity (viz., urease) and noticed diat the degree of degradation of this highlypurificd protein could be correlated with the disappearance of the associated enzymatic activity. Before that time, it was thought that enzymes might be special nonprotein substanccs that happened to be associated with proteins. In other words, it was thought diat some proteins might simply serve as passive, structural supports for enzymes. On the other hand, Sumner's discovery suggested that the enzymatic activity was related to the structure of the protein per sc. In the 1930s Northrop and Kunitz purified and crystallized many enzymatic proteins and, thus, confirmed Sumner as the father of modern cnzymatology.