The following timeline is based upon the book Nature's Robots - A History of Proteins by Charles Tanford and Jacqueline Reynolds (Oxford University Press, 2001, 304 pages). Page references below refer to this fascinating and eminently readable account, which contains the original literature citations. Nature's Robots is highly recommended!

• 1789: Antoine Fourcroy distinguishes several types of proteins (then called "albumins" or "Eiweisskörper") such as albumin, fibrin, gelatin, and gluten. (p. 11)

• 1819: Leucine is the first amino acid isolated. The 20th, threonine, was not discovered until 1936. Asparagine had been isolated and named in 1809 because of its ready crystallization from asparagus shoots, but its role as a constituent of protein was not recognized until 1873, and proof, by protein hydrolysis under conditions that do not break side-chain amide bonds, did not come until 1932. (p. 30)

• 1837: Gerrit J. Mulder determines the elemental composition of several proteins, and recognizes that they have a single common core substance. He proposes that this Grundstoff is synthesized by plants and transferred intact into herbivores and then into carnivores. His empirical formula for fibrin and egg albumin: C₄₀₀H₆₂₀N₁₀₀O₁₂₀P₁S₁ (p. 14). At this time, only glycine and leucine were known among the amino acids (p. 30).

• 1838: Jacob Berzelius, in response to Mulder's results, proposed the name protein from the greek prwteioz, "standing in front", to designate "the primitive or principal substance of animal nutrition". (p. 15)

• 1840: Hemoglobin crystals are reported in smears of earthworm blood. (. 22)

• 1855: Naturally occurring protein crystals are purified from plant seeds. (p. 27)

• 1874: van't Hoff describes the relationship between molecular asymmetry and optical rotation for simple organic compounds. (p. 31)

• 1886: Oscar Zinoffsky concluded that the minimal molecular weight of hemoglobin is 16,700, with 1 iron and 2 sulfurs per molecule. (p. 45) This was confirmed in 1894 when a similar weight of hemoglobin was shown capable of binding one oxygen molecule. (cf. 1910)

• 1889: Franz Hofmeister crystallizes egg albumin (p. 27)

• ~1890: A. Sabanjeff estimates the molecular weight of ovalbumin is 15,000 using freezing point depression. (p. 46; cf. 1915)

• 1902: Emil Fisher and Franz Hofmeister (independently) discover the peptide bond. (p. 31)

• 1907-8: Committees in England and the USA standardise the term protein (recommending that the term "proteid" be discontinued) and standardise the definitions of albumins, globulins, glutelins, and histones based on their solubility properties. (p. 84)

• 1909: E. T. Reichert and A. P. Brown show that hemoglobins from diverse species crystallizes in different forms, and therefore most likely is not identical. Say Tanford and Reynolds "No comparable effort had at that time ever been expended in investigating species differences at the molecular level". (emphasis added, p. 23)

• 1910: J. Barcroft and A. V. Hill estimate the minimal molecular weight of hemoglobin to be 16,000 by thermodynamic calorimetry of oxygen binding. (p. 54; cf. 1886, 1926)

• 1915: S. P. L. Sørensen et al. estimate the molecular weight of ovalbumin to be 34,000 using osmometry. (p. 53; cf. 1890)

• 1920: Hermann Staudinger was "the first effective proponent of the idea that true molecules of huge size are capable of stable existence". The alternative popular at the time among organic chemists: proteins are colloids composed of "loose associations of much smaller molecules". (p. 43; cf. 1886, 1837)

• ~1925: N. Bjerrum, E. Q. Adams, K. Linderstrøm-Lang and others reach consensus about the zwitterionic character of proteins at the isoelectric pH. Previously it was thought that an uncharged molecule meant the absence of charges, and acids and bases were thought of as separate categories, rather than poles of a single continuum. (p. 67 and Chapter 5)

• 1925: G. S. Adair determines the molecular weight of hemoglobin to be 65,000 by osmometry. Independently, T. Svedberg gets the same result by ultracentrifugal sedimentation velocity. (p. 104; cf. 1886, 1910, 1926)

• 1926: J. B. Sumner crystallizes the first enzyme, jackbean urease. (p. 28).

• 1926: T. Svedberg (Nobel Prize in Chemistry, 1926) and R. Fähraeus found hemoglobin to sediment in monodisperse fashion at four-times the well-established minimum molecular weight. (p. 58; cf. 1886, 1910, 1925)

• 1930: W. T. Astbury reports fiber periodicities in wool and hair, reversibly stretched, dubbing the two forms a-keratin and b-keratin. These were in fact helices and sheets, and are the origins of the a and b used in secondary structure nomenclature today. (p. 81) Astbury proposed that the a and b conformations seen in fibers may underlie the structures of globular proteins, and he also proposed the notion of interchain cystine bonds. (p. 83)

• 1934: J. D. Bernal and Dorothy Crowfoot Hodgkin obtain the first sharp X-ray diffraction pattern for a crystalline protein (pepsin), confirming its compact globular shape and discovering the importance of water for maintaining conformational stability. Atomic resolution of proteins seems possible but not in reach. (p. 113, 141)

• 1936: Threonine is identified as the 20th amino acid. 18 had been identified by 1903; methionine was identified in 1922. (p. 30; cf. 1819)

• 1937: A. Tiselius (Nobel Prize in Chemistry, 1948) devises preparative electrophoretic methods to separate serum proteins into four major groups (albumins and a, b, g globulins) and identifies antibody as a gamma-globulin. (p. 87)

• 1941: A. J. P. Martin and R. L. M. Synge (Nobel Prize in Chemistry, 1952) adapt M. S. Tswett's method of chromatography (1906) to separate amino acids from protein hydrolysates. Quantitation remained problematic. (p. 91)

• 1949: S. Moore and W. H. Stein perfect quantitative amino acid composition analysis using starch column chromatography with ninhydrin. (p. 95)

• 1949: Linus Pauling et al. distinguish normal from sickle hemoglobin by electrophoresis. (p. 101)

• 1951: Fredeick Sanger sequences the beta chain of insulin. The alpha chain sequence was reported in 1953, and the disulfide bond locations in 1955. (p. 98; Nobel Prize in Chemistry, 1958)

• 1958: John C. Kendrew et al. publish a low-resolution (6-7 Å) crystal structure for myoglobin -- the first folded protein 3D structure. It lacked symmetry or anticipated regularities, being more complicated than predicted. (p. 146)
  
  

  I am continuing to work on this -- it is not yet anywhere near being finished.