Here I will provide a few notes on the history of peptide science in Denmark. As with many other useful names and concepts, it is difficult to give a short description of what ‘peptide science’ is that everybody will agree to. Similar for peptide science and the peptide community in Denmark. I am sure that, despite my best effort, I will have missed contributions and scientists. I hope for forgiveness.
Brief historical introduction
An obvious place to start is with August Krogh (1874-1949) and his wife Marie Krogh (1874-1865), who was also an accomplished scientist. August Krogh, who had received the Nobel Prize in Medicine in 1920, went on a lecture tour in the USA with his wife Marie Krogh in 1922. There they learned that John Macleod and coworkers in Toronto has succeeded in isolating insulin. Marie Krogh had diabetes and they eventually travelled to Toronto. They received permission to start an insulin production in Denmark. They worked with Hans Christian Hagedorn and founded Nordisk Insulin Laboratorium. Later, a competing company was founded by two former employees at Insulin Laboratorium, Thorvald and Harald Pedersen, who started Novo Terapeutisk Laboratorium. These two companies continued to compete until they merged in 1989, after 65 years. This became Novo Nordisk A/S. A large part of the income from Novo Nordisk A/S goes to the Novo Nordisk Foundation, which is now one of the largest private foundations supporting research.
The 16th European Peptide Symposium was held in Helsingør, Denmark, in 1980. It was organized by Kay Brunfeldt (1919-1996), who had been active in the broader field of peptide science most of his career. He had worked with Peter Roepstorff (1942-) on developing one of the very first automated solid-phase peptide synthesizers. Roepstorff then worked extensively on developing the fundamental methods for mass spectrometry of peptides in the 1980’s and 1990’s at University of Southern Denmark. At the University of Copenhagen, Faculty of Health and Medical Sciences, Jens Juel Holst (1945 -) made key contributions to understanding the function of GLP-1. This set the stage for the development of GLP-1 analogs for the treatment of first type 2 diabetes and then also treatment of obesity
Meanwhile at the Department of Chemistry at the University of Copenhagen, Arne Holm was the first in Denmark to establish a research group dedicated to peptide chemistry. He was joined by a young assistant professor named Morten Meldal. Arne Holm had a sabbatical with Bruce Merrifield at Rockefeller University, while Morten had just returned from a postdoc with Robert (Bob) C. Sheppard at the MRC Laboratory of Molecular Biology. With his group Arne Holm moved to the Royal Veterinary and Agricultural University and founded Centre for Biotechnology in collaboration with several other professors such as Elisabeth Bock (Protein laboratory), Keld Danø (Finsen Institute) and Ivar Heron (Staten Serum Institute) to name a few. Chemistry and biology of peptides were central to this interdisciplinary collaboration. Some of Arne Holm’s former coworkers went on to become prominent scientists, including Bjarne Due Larsen, Søren Østergaard, Thomas Hoeg-Jensen and Paul R. Hansen.
Morten Meldal moved from the University of Copenhagen to the Carlsberg Laboratory in 1988, where he spend a large segment of his career, but since 2011 he is again at the University of Copenhagen. Morten’s scientific career was crowned when he was awarded a share of the 2022 Nobel Prize in chemistry. Morten Meldal and Christian W. Tornøe discovered CuAAC, while Christian was a PhD student there. I have written more about Morten other places.
In the 1990’s at the University of Copenhagen, PNA was invented and developed by Michael Egholm, Rolf Berg, Peter Nielsen, and Ole Buchardt, at University of Copenhagen.
The 31st European Peptide Symposium was held in Copenhagen in 2010 and was co-chaired by Morten Meldal, Thomas Hoeg-Jensen, and myself.
Pharmaceutical peptide research is also pursued at the Department of Pharmacy and Pharmacology at the University of Copenhagen. Hanne Mørck Nielsen has a focus on transport of peptides across barriers, in particular for oral delivery of peptides. While Kristian Strømgaard at the Department of Drug Design focuses on drug discovery, where he has explored protein protein interactions with peptide array technologies. This work involved collaboration with many academic groups spread out over in Europe. He has founded the successful peptide-based biotech Avilex. Christian Adam Olsen is exploring peptide mimetic scaffolds and macrocyclic peptides.
As for myself, I was one of Mortens’ first graduate students and moved with him to the Carlsberg Laboratory. My own research group is now at the Department of Chemistry, University of Copenhagen. We developed methods for solid-phase peptide synthesis, including methods for microwave heating, insulin chemistry, incretin hormones, technology for derivatization of proteins, and more. I have collaborated with biotech Gubra A/S since its start.
Companies
Most of the pharmaceutical industries in Denmark are located in the Copenhagen region. Jan Markussen and Niels Langeland Johansen were both pioneers in peptide medicinal chemistry at Novo Nordisk A/S where the former made an efficient procedure for transforming animal insulin into human insulin by an enzymatic process. During Jan Markussen’s leadership, Novo Nordisk also invented the fatty acid acylation technology for half-life extension of peptides and proteins, a technology that has transformed the peptide pharmaceutical landscape. It was first implemented on insulin but was later used for GLP-1 analogs and many other peptides. This fatty acid technology was also developed by Thomas Hoeg-Jensen in the design of insulin degludec and insulin analogues with glucose responsiveness. Søren Østergaard explored combinatorial libraries of fatty acids, designed insulin mimetics and later GLP-1 analogues. In the development of GLP-1 peptides as successful drugs at Novo Nordisk, Lotte Bjerre Knudsen was a central scientist and crucial driving force. Thomas Kruse and Jesper Lau had key roles in the discovery and development of semaglutide. In addition, Thomas also contributed to Novo Nordisk’s amylin obesity drugs. Another large pharma company involved in peptides and proteins is Ferring Pharmaceuticals which has a major research and development site in Copenhagen site.
The Copenhagen “Medicon Valley” is also famous for its many small and larger biotech companies engaged in peptide technology and biology. Bjarne Due Larsen co-founded Zealand Pharma A/S, which has developed approved peptide drugs. Gubra which was founded in 2007, is exploring peptides in their own discovery programs and utilize high-throughput technologies to speed up the drug discovery process. Smaller peptide companies include Immunitrack, now part of Lilly, and is pursuing high throughput synthesis of neoepitopes, Pephexia founded by Keld Fosgerau and Søren L. Pedersen is involved in treatment options for cachexia. Schafer-N founded by Claus Schafer-Nielsen is doing custom peptide arrays.
I thank Søren Østergaard for very valuable discussions.
References
- Kurt Jacobsen, Novo Nordisk, Gads Forlag, København, 2023.
- The history of the Novo Nordisk Foundation: https://novonordiskfonden.dk/en/who-we-are/our-history/
- Rolf H Berg, Kay Brunfeldt (1919-1996), The European Peptide Society Newsletter, 16, April 1997.
- Knud J. Jensen, 2022 Nobel Prize in Chemistry awarded to Morten Meldal, The European Peptide Society, October 8 2022; (https://www.eurpepsoc.com/2022-nobel-prize-in-chemistry-awarded-to-morten-meldal/)
Contributed by Knud J. Jensen