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Christian A. Olsen Group. HDAC inhibitors
University of Copenhagen. Center for Biopharmaceuticals. Universitetsparken 2 2100 Copenhagen

KDACs, sirtuins, macrocycles, enzyme inhibitors, substrates, photo cross-linking probes



Organic synthesis, peptide synthesis, peptide macrocyclization, in vitro assay development

Collaborations outside COST

Prof. Hirshey (Duke University), Prof. Ghadiri (Scripps Research Institute), Prof. Ingmer (University of Copenhagen).

Short description of ongoing research projects

With a foundation in chemical synthesis, we seek to explore the function of small molecules, peptides, peptidomimetics, and proteins in biological systems. We are focusing on peptidomimetic secondary structures with potential as antimicrobial agents, as non-proteinogenic ligands for disruption of protein–protein interactions, and for multivalent display. We are also exploring naturally occurring macrocyclic peptides – and analogues thereof – for development of class- or isoform-selective HDAC inhibitors and quorum sensing modulators, as well as investigating substrate-specificity of the human lysine deacylase enzymes using chemical biology tools.

  1. A. R. Maolanon, J. S. Villadsen, N. J. Christensen, C. Hoeck, T. Friis, P. Harris, C. H. Gotfredsen, P. Fristrup, C. A. Olsen. Methyl Effect in Azumamides Provides Insight Into Histone Deacetylase Inhibition by Macrocycles. J. Med. Chem. 2014, 57, 9644–9657.
  2. J. S. Villadsen, B. Kitir, K. Wich, T. Friis, A. S. Madsen, C. A. Olsen.* A Macrocyclic Azumamide Analogue without the Zinc-Binding Functionality. Med. Chem. Commun. 2014, 5, 1849–1855. (Special issue on epigenetics).
  3. M. Tan, C. Peng, K. A. Anderson, P. Chhoy, Z. Xie, L. Dai, J. S. Park, Y. Chen, H. Huang, Y. Zhang, J. Ro, G. R. Wagner, M. F. Green, A. S. Madsen, J. Schmiesing, B. S. Peterson, G. Xu, O. R. Ilkayeva, M. J. Muehlbauer, T. Braulke, C. Mühlhausen, D. S. Backos, C. A. Olsen, P. J. McGuire, S. D. Pletcher, D. B. Lombard, M. D. Hirschey, Y. Zhao. Lysine Glutarylation Is a Protein Modification Regulated by SIRT5. Cell Metab. 2014, 19, 605–617.
  4. A. S. Madsen, H. M. E. Kristensen, G. Lanz, C. A. Olsen.* The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11. ChemMedChem. 2014, 9, 614–626.
  5. J. S. Villadsen, H. M. Stephansen, A. R. Maolanon, P. Harris, C. A. Olsen.* Total Synthesis and Full Histone Deacetylase Inhibitory Profiling of Azumamide A–E as Well as beta2-Epi-Azumamide E and beta3-Epi-Azumamide. J. Med. Chem. 2013, 56, 6512–6520.
Other activities of potential interest to others

Cost UE