Peptide science is little more than a century old, yet it has produced some of medicine's most important molecules and at least five Nobel Prizes. This is the story of how chemists learned first to understand peptides, then to build them.
1900s: the first synthetic peptide
In 1901 the German chemist Emil Fischer, working with Ernest Fourneau, reported the synthesis of glycylglycine, the first synthetic dipeptide. Fischer also coined the word "peptide" and proposed that proteins are long chains of amino acids linked by amide bonds. That idea now seems obvious, but at the time it was a bold hypothesis.
1920s: insulin changes everything
In 1921 Frederick Banting and Charles Best, working in J.J.R. Macleod's laboratory in Toronto, isolated insulin from pancreatic extracts. Within a year it was being used to treat people with type 1 diabetes, until then a fatal condition. Banting and Macleod received the 1923 Nobel Prize in Physiology or Medicine. For decades afterwards, insulin was extracted from cattle and pig pancreases.
1950s: sequencing and synthesis
- Frederick Sanger worked out the complete amino acid sequence of insulin between 1951 and 1955. That proved, for the first time, that a protein has one precise, defined sequence. He received the 1958 Nobel Prize in Chemistry, the first of his two.
- Vincent du Vigneaud synthesised the hormone oxytocin in 1953, the first peptide hormone made in a laboratory. It earned him the 1955 Nobel Prize in Chemistry.
1960s: the solid-phase revolution
Making peptides in solution was slow, because every intermediate had to be purified. In 1963 Bruce Merrifield published solid-phase peptide synthesis, which anchors the growing chain to a polymer bead so reagents can simply be washed away. The method could be automated, and it reduced months of work to days. Merrifield received the 1984 Nobel Prize in Chemistry.
In 1970 Louis Carpino and Grace Han introduced the Fmoc protecting group. Its milder chemistry later became the dominant approach in peptide synthesis.
1980s: biology takes over production
Recombinant DNA technology meant cells could be engineered to produce human peptides. In 1982 recombinant human insulin, made by genetically modified bacteria, became the first approved medicine produced this way. That ended the dependence on animal pancreases.
1990s–2000s: nature as a source
Researchers increasingly turned to venoms, skin secretions and microbes for peptide leads. Exenatide, based on a peptide found in Gila monster saliva, and ziconotide, derived from cone snail venom, both became approved medicines in the mid-2000s.
2018 and beyond: evolution in a test tube
The 2018 Nobel Prize in Chemistry recognised George Smith and Sir Gregory Winter for phage display, which lets researchers screen billions of peptide and antibody variants for binding to a target. Together with computational design and AI-based structure prediction, these tools define the modern era of peptide research.
Timeline: 1901 first synthetic dipeptide · 1921 insulin isolated · 1953 oxytocin synthesised · 1955 insulin sequenced · 1963 solid-phase synthesis · 1982 recombinant insulin · 1985 phage display · 2018 Nobel for directed evolution
Related articles
- How peptide receptors work: GPCRs explained
- Peptide structure: from sequence to shape
- Peptides in nature: the body's messengers
Sources and further reading
- Fischer E, Fourneau E. Ueber einige Derivate des Glykocolls. Ber Dtsch Chem Ges 1901;34:2868–2877. doi:10.1002/cber.190103402249
- The Nobel Prize in Physiology or Medicine 1923 (Banting, Macleod). www.nobelprize.org/prizes/medicine/1923/summary
- The Nobel Prize in Chemistry 1955 (du Vigneaud). www.nobelprize.org/prizes/chemistry/1955/summary
- The Nobel Prize in Chemistry 1958 (Sanger). www.nobelprize.org/prizes/chemistry/1958/summary
- Merrifield RB. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 1963;85:2149–2154. doi:10.1021/ja00897a025
- The Nobel Prize in Chemistry 1984 (Merrifield). www.nobelprize.org/prizes/chemistry/1984/summary
- Carpino LA, Han GY. 9-Fluorenylmethoxycarbonyl function, a new base-sensitive amino-protecting group. J Am Chem Soc 1970;92:5748–5749. doi:10.1021/ja00722a043
- Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 1985;228:1315–1317. doi:10.1126/science.4001944 · PMID: 4001944
- The Nobel Prize in Chemistry 2018 (Arnold, Smith, Winter). www.nobelprize.org/prizes/chemistry/2018/summary
- Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem 2018;26:2700–2707. doi:10.1016/j.bmc.2017.06.052 · PMID: 28720325