In 1953 Staub, Sinn, and Behrens1 announced the preparation of crystalline glucagon, thus making available a small protein ideally suited for fundamental chemical and biological studies. As a part of these studies, research was initiated on structural aspects of the protein molecule. This report comprises a brief summary2 of the work leading to the elucidation of the complete amino acid sequence of glucagon.

It is pertinent to consider briefly some of the reasons that such structural studies were attempted. Perhaps the principal motive behind protein structure research is not merely to reveal the amino acid sequence of the protein, but more important, to lay the foundation for understanding the biological activity of the protein on a molecular basis. For example, it might be asked what specific arrangement of amino acids or what chemical groupings are necessary in the glucagon molecule to elicit such a marked hyperglycemic response? Does a smaller portion of the glucagon chain retain activity? Why does glucagon have this effect, while insulin has another, and many other proteins have no known biological activity at all? Determination of the amino acid sequence is an important step leading to the understanding of the fundamental relationships between protein structure and activity.