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Timeline of peptide research
From insulin (1921) to the modern incretin line, the milestones of peptide science, with sources.
Insulin: the first major peptide hormone put to use
Banting and Best (Macleod’s lab, University of Toronto) produced a pancreatic extract that lowered blood sugar; Collip purified it. In early 1922 the first patient received it. Insulin is a peptide hormone.
Source: Nobel Prize in Medicine 1923 · nobelprize.orgFirst synthesis of a peptide hormone (oxytocin)
Vincent du Vigneaud determined the amino-acid sequence of oxytocin and synthesised it in 1953, the first artificially made peptide hormone. Nobel Prize in Chemistry 1955.
Source: Nobel Prize in Chemistry 1955 · nobelprize.orgSanger determines the full amino-acid sequence of insulin
Frederick Sanger was the first to map the complete amino-acid sequence of a protein, that of insulin, including its two chains and how they are linked. It was the first time the structure of a protein had been fully determined. Nobel Prize in Chemistry 1958.
Source: Nobel Prize in Chemistry 1958 · nobelprize.orgSolid-phase peptide synthesis (SPPS)
Bruce Merrifield published a method building the peptide while attached to a solid resin bead, faster, more reliable, later automatable. Still the basis of modern peptide production. Nobel Prize in Chemistry 1984.
Source: Merrifield, J. Am. Chem. Soc. 1963 · DOI 10.1021/ja00897a025Amino-acid sequence determines how a protein folds
Working with the enzyme ribonuclease, Christian Anfinsen showed that the amino-acid sequence itself determines how the chain folds into its active form, with no extra information needed. Stanford Moore and William Stein clarified the active centre of the same enzyme. Nobel Prize in Chemistry 1972.
Source: Nobel Prize in Chemistry 1972 · nobelprize.orgRadioimmunoassay makes peptide hormones measurable in blood
Rosalyn Yalow developed the radioimmunoassay, a method able to measure extremely low concentrations of peptide hormones in blood, down to the billionth of a gram. It gave researchers their first sensitive way to quantify these substances. Nobel Prize in Physiology or Medicine 1977.
Source: Nobel Prize in Medicine 1977 · nobelprize.orgFirst human insulin made with recombinant DNA
In 1982 the US FDA approved human insulin produced by genetically modified bacteria. It was the first biosynthetic human insulin product and the first medicine made with recombinant DNA technology, a turning point for biotechnology.
Source: Recombinant DNA insulin, first biotech medicine 1982 · nsf.govGLP-1 characterised
Glucagon-like peptide-1 (GLP-1) is described as a gut hormone influencing insulin release, the start of the incretin research line.
Source: Drucker, review 2017 · PubMed 29202475Exendin-4 discovered
John Eng found exendin-4 in the venom of the Gila monster lizard, a naturally stable GLP-1-like peptide that became the basis for the first incretin research lines.
Source: Drucker, review 2017 · PubMed 29202475Ghrelin and the growth-hormone line
Kojima and colleagues described ghrelin, a stomach peptide that stimulates growth-hormone release, the natural ligand of the growth-hormone secretagogue receptor.
Source: Kojima, review · Ann. NY Acad. Sci. 2010Mass spectrometry and NMR for large biomolecules
The 2002 Nobel Prize in Chemistry was awarded for methods to identify and analyse the structure of large biomolecules. John Fenn and Koichi Tanaka developed soft ionisation for mass spectrometry of proteins, and Kurt Wüthrich developed NMR to determine the three-dimensional structure of proteins in solution.
Source: Nobel Prize in Chemistry 2002 · nobelprize.org