Editing Protein primary structure (section)

==History==
The proposal that proteins were linear chains of α-amino acids was made nearly simultaneously by two scientists at the same conference in 1902, the 74th meeting of the Society of German Scientists and Physicians, held in Karlsbad. [[Franz Hofmeister]] made the proposal in the morning, based on his observations of the biuret reaction in proteins. Hofmeister was followed a few hours later by [[Hermann Emil Fischer|Emil Fischer]], who had amassed a wealth of chemical details supporting the peptide-bond model. For completeness, the proposal that proteins contained amide linkages was made as early as 1882 by the French chemist E. Grimaux.<ref name="history">{{cite journal |author=Fruton JS |title=Early theories of protein structure |journal=Ann. N. Y. Acad. Sci. |volume=325 |pages=xiv, 1–18 |date=May 1979 |issue=1 |pmid=378063 |doi=10.1111/j.1749-6632.1979.tb14125.x |bibcode=1979NYASA.325....1F |s2cid=39125170 }}</ref>

Despite these data and later evidence that proteolytically digested proteins yielded only oligopeptides, the idea that proteins were linear, unbranched polymers of amino acids was not accepted immediately. Some scientists such as [[William Astbury]] doubted that covalent bonds were strong enough to hold such long molecules together; they feared that thermal agitations would shake such long molecules asunder. [[Hermann Staudinger]] faced similar prejudices in the 1920s when he argued that [[rubber]] was composed of [[macromolecule]]s.<ref name="history"/>

Thus, several alternative hypotheses arose. The '''colloidal protein hypothesis''' stated that proteins were colloidal assemblies of smaller molecules. This hypothesis was disproved in the 1920s by ultracentrifugation measurements by [[Theodor Svedberg]] that showed that proteins had a well-defined, reproducible molecular weight and by electrophoretic measurements by [[Arne Tiselius]] that indicated that proteins were single molecules. A second hypothesis, the '''[[cyclol]] hypothesis''' advanced by [[Dorothy Wrinch]], proposed that the linear polypeptide underwent a chemical cyclol rearrangement C=O + HN <math>\rightarrow</math> C(OH)-N that crosslinked its backbone amide groups, forming a two-dimensional ''fabric''. Other primary structures of proteins were proposed by various researchers, such as the '''diketopiperazine model''' of [[Emil Abderhalden]] and the '''pyrrol/piperidine model''' of Troensegaard in 1942. Although never given much credence, these alternative models were finally disproved when [[Frederick Sanger]] successfully sequenced [[insulin]]{{when|date=May 2019}} and by the crystallographic determination of myoglobin and hemoglobin by [[Max Perutz]] and [[John Kendrew]]{{when|date=May 2019}}.