Research in the Nanobioorganic Chemistry group focuses on the interface of synthetic (bio-)organic chemistry, biology, medicinal chemistry and nanobioscience. The starting point in our research is often synthetic peptide chemistry, carbohydrate chemistry, organic chemistry on proteins, or chemistry on nanoparticles or surfaces.
The development of new, general chemical tools that enables us to contribute to chemical biology. Solid-phase peptide synthesis plays a central role, both for the fully automated preparation of peptides and in the development of new chemical methods. We are developing new linkers, incl. for the synthesis of peptide thioesters, and are developing the application of microwave heating in peptide synthesis.
Regioselective synthetic chemistry on proteins is a growing interest in our group. For example, we have designed and chemically synthesized new insulin variants with abiotic ligands, such as bipyridine for nano-scale self-assembly with Fe(II), or perfluoroalkyl chains for self-assembly driven by the ‘fluorous’ effect.
Another focus is chemoselective carbohydrate chemistry where it enables the construction of complex glycoconjugates, glyconanoparticles, covalent glycan microarrays etc.
We aim to study fundamental biological questions in collaboration with dedicated biology groups and to develop new methods for peptide medicinal chemistry. In medicinal chemistry we focus on peptide hormone derived drug candidates for the treatment of metabolic diseases and on protease inhibitors for intervention in cancer. We are enjoying collaborations with several biophysics groups. A special focus is on determination of protein topologies using small angle X-ray scattering, SAXS, and on the interaction of peptides with membranes.
Our research is focused on the interface between synthetic bioorganic chemistry, biology, biophysics, medicinal chemistry, and nanotechnology. We are in the section for chemical biology at the Department of Chemistry.
We seek to define and exploit the laws governing selfassembly of biomolecules in order to build biological meaningful nano-scale structures. The aim is to understand and control the self-assembly of biomolecules in solution and on surfaces. The ability to make defined nano-scale structures of biomolecules leads directly to biomedical applications, including nanomedicine.
Organic synthesis is a powerful tool for the design and preparation of new materials on the Ångstrøm and nanometer-length scale. We use a combination of solution and solid-phase based organic chemistry to synthesize complex biomolecules, such as peptides, glyco-conjugates (carbohydrates), and even small proteins. We also develop new chemistry, including new reagents, to aid us in the synthesis of complex biomolecules. For example, we are working with designer proteins, which are man-made protein-like molecules with an artificial structure, which we are using in studies on self-assembly, both in solution and as self-assembled monolayers on surfaces. To study these structures, we collaborate with biophysicist and physical chemists. We are using the knowledge gained in these studies in collaboration with partners from the biopharmaceutical industry.
In one line of research, we are anchoring abiotic ligands covalently and regioselectively to proteins to control their self-assembly at the nano scale. We have shown that non-native bipyridine ligands can be used to control the higher-ordered self-assembly of insulin.
The use of Fe(II) provided chemoselective binding over the native site, forming a homo-trimer in a reversible manner, which was easily followed by the characteristic color of the Fe(II) complex. This provided the first well-defined insulin 18-mer and the first insulin variant where self-assembly can be followed visually.
Knud J. Jensen (Ed.), Peptide and Protein Design for Biopharmaceutical Applications: https://onlinelibrary.wiley.com/book/10.1002/9780470749708
Michael Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Eds.), Proceedings of the 31st European Peptide Sympoisum, Copenhagen, 2010: Download:http://www.5z.com/31eps/book/Proc31EPS_v4.1_web.pdf
Knud J. Jensen and Anita Kildebæk Nielsen (Eds), Aspects of Philosophy of Chemistry http://nyttf.dk/?pagetype=book&vareid=84020-1
Some recent highlights
A. Pernille Tofteng, Søren L. Pedersen, Dan Staerk, Knud J. Jensen, Effect of Residual Water and Microwave Heating on Half-Lifes of Reagents and Reactive Intermediates in Peptide Synthesis, Chemistry – European Journal, 2012, 18, 9024-9031.
Angelique Broghammer, Lene Krusell, Mick Blaise, Nicolai Maolanon, John T. Sullivan, Jørgen Sauer, Maria Vinther, Andrea Lorentzen, Knud J. Jensen, Peter Roepstorff, Søren Thirup, Clive W. Ronson, Mikkel B. Thygesen, Jens Stougaard, Legume receptors perceive the bacterial lipochito-oligosaccharide signal molecules by direct binding, 2012, PNAS, 109 (34), 13859-13864.
Søren L. Pedersen, A. Pernille Tofteng, Leila Malik, Knud J. Jensen, Microwave heating in solid-phase peptide synthesis, Chem. Soc. Rev., 2012, 41, 1826-1844.
Leila Malik, Jesper Nygaard, Rasmus Høiberg-Nielsen, Lise Arleth, Thomas Høeg-Jensen, Knud J. Jensen, Perfluoroalkyl Chains Direct Novel Self-Assembly of Insulin, Langmuir, 2011, 28, 593-603.
Henrik K. Munch, Søren T. Heide, Niels J. Christensen, Thomas Hoeg-Jensen, Peter W. Thulstrup and Knud J. Jensen, Controlled Self-Assembly of Re-engineered Insulin by FeII, Chem. Eur. J., 2011, 17 (26), 7198-7204.
Mikkel B. Thygesen, Henrik Munch, Jørgen Sauer, Emiliano Clo, Malene R. Jørgensen, Ole Hindsgaul, and Knud J. Jensen, Nucleophilic Catalysis of Carbohydrate Oxime Formation by Anilines, Journal of Organic Chemistry, 2010, 75, 1752-1755
Emiliano Cló, Ola Blixt, and Knud J. Jensen, Chemoselective Reagents for Covalent Capture and Display of Glycans in Microarrays, European Journal of Organic Chemistry, 2010, 540.
A. Pernille Tofteng, Kasper K. Sørensen, Kilian W. Conde-Frieboes, Thomas Hoeg-Jensen, Knud J. Jensen, Fmoc Solid-Phase Synthesis of C-Terminal Peptide Thioesters via Formation of a Backbone Pyroglutamyl Imide Moiety, Angewandte Chemie, 2009, 48, 7411-7414.
Mikkel B. Thygesen, Kasper K. Sørensen, Emiliano Cló, Knud J. Jensen, Direct chemoselective synthesis of glyconanoparticles from unprotected reducing glycans and glycopeptide aldehydes, Chemical Communications, 2009, 6367-6369.
Mikkel. B. Thygesen, J. Sauer, Knud J. Jensen, Chemoselective capture of glycans for analysis on Gold nanoparticles: Carbohydrate Oxime Tautomers Provide Functional Recognition by Proteins, Chemistry – European Journal, 15, 2009, 1649-1660.
Mikkel B. Thygesen, associate professor
Knud J. Jensen, professor
Department of Chemistry, University of Copenhagen, Thorvaldsensvej 41, DK-1871 Frederiksberg C
Knud Jørgen Jensen
Phone: +45 2151 6721