Employees – University of Copenhagen

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Department of Drug Design and Pharmacology > Employees

Andreas Stahl Madsen

Andreas Stahl Madsen

Assistant professor

Education
2010. PhD in Chemistry, University of Southern Denmark
2008. Visiting Scholar, Stanford University, USA
2008. Cand. Scient. in Pharmaceutical Chemistry, University of Southern Denmark
2004. B.Sc. in Pharmaceutical Chemistry, University of Southern Denmark

Employment
2014 – present. Assistant Professor, University of Copenhagen
2013 – 2014. Sapere Aude Post. Doc., Technical University of Denmark
2010 – 2013. Post. Doc., Technical University of Denmark
2010. Post. Doc., University of Southern Denmark
2008 - 2010. PhD student, University of Southern Denmark

Grants and awards
2012. Sapere Aude DFF Postdoctoral Grant, The Danish Council for Independent Research | Technology and Production Sciences
2012. Individual Postdoctoral Grant, The Danish Council for Independent Research | Technology and Production Sciences
2007. EliteForsk Traveling Grant, The Danish Ministry of Sci., Technol. and Innovation
2005. Oticon Scholarship, The Oticon Foundation, Scholarship and Grant for equipment

Selected Publications

S. Karmakar, A. S. Madsen, D. C. Guenther, B. C. Gibbons, P. J. Hrdlicka. Recognition of double-stranded DNA using energetically activated duplexes with interstrand
zippers of 1-, 2- or 4-pyrenyl-functionalized O2'-alkylated RNA monomers. Org. Biomol. Chem. 2014, 12, 7758–7773

J. S. Villadsen, B. Kitir, K. Wich, T. Friis, A. S. Madsen, C. A. Olsen. An azumamide C analogue without the zinc-binding functionality. Med. Chem. Commun. 2014, 5, 1849–1855

M. Tan, C. Peng, K. A. Anderson, P. Chhoy, Z. Xie, L. Dai, J. Soon 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 Posttranslational Modification Regulated by SIRT5. Cell Metab. 2014, 19, 605–617

A. S. Madsen, H. M. E. Kristiansen, G. Lanz, C. A. Olsen. The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11. ChemMedChem 2014, 9, 614–626

S. P. Sau, A. S. Madsen, P. Podbevsek, N. K. Andersen, T. S. Kumar, S. Andersen, R. L. Rathje, B. A. Anderson, D. C. Guenther, S. Karmakar, P. Kumar, J. Plavec, J. Wengel, P. J. Hrdlicka. Identification and Characterization of Second-Generation Invader Locked Nucleic Acids (LNAs) for Mixed-Sequence Recognition of Double-Stranded DNA. J. Org. Chem. 2013, 78, 9560–9570

A. S. Madsen, A. S. Jørgensen, T. B. Jensen, J. Wengel. Large Scale Synthesis of 2′-Amino-LNA Thymine and 5‑Methylcytosine Nucleosides. J. Org. Chem. 2012, 77, 10718–10728

A. S. Madsen, C. A. Olsen. Profiling of Substrates for Zinc-dependent Lysine Deacylase Enzymes: HDAC3 Exhibits Decrotonylase Activity In Vitro. Angew. Chem. Int. Ed. 2012, 51, 9083–9087

A. S. Madsen, C. A. Olsen. Substrates for Efficient Fluorometric Screening Employing the NAD-Dependent Sirtuin 5 Lysine Deacylase (KDAC) Enzyme. J. Med. Chem. 2012, 55, 5582–5590

A. S. Madsen, J. Wengel. Oligonucleotides with 1,4-Dioxane-Based Nucleotide Monomers. J. Org. Chem. 2012, 77, 3878-3886

Current research

Chemical Tools for Unraveling the Importance of the Lysine Deacylase (KDAC) Enzymes

The research is supported by a Sapere Aude DFF Individual Postdoctoral Grant

The lysine deacylase (KDAC) enzymes catalyze hydrolytic removal of acyl functionalities from the ε-amino group of lysine residues in a variety of proteins including histones. Posttranslational modification (PTM) play major roles in regulation of protein function, and while primary targets of some KDACs appear to be ε-N-acetylated lysine residues of histone proteins, recent discoveries have revealed lysine acetylation as a general PTM in proteins, and a growing list of non-histone proteins are identified as substrates for the KDACs, thereby extending their potential impact on cell function.

In addition to lysine acetylation, additional acyl groups have also been identified as PTMs of lysine residues in histones and other proteins. These modifications include formylation, propionylation, butyrylation and myristoylation, and within the past few years, the list of acyl groups has been extended considerably to also include crotonyl, malonyl, succinyl, glutaryl, 3-phosphoglycinyl, and α-hydroxyisobutyryl. THese findings expand the scope of acyl-based PTMs considerably.

Interestingly, sirtuins 5 and 6 have recently been demonstrated to catalyze demalonylation, desuccinylation, deglutarylation and demyristoylation of protein and peptide substrates. These findings suggest that KDACs with impaired deacetylase activity might in fact be functional deacylases catalyzing hydrolysis of other acylamides.

To address the intriguing expanded cellular repertoire of KDACs, the present project aim at expanding the current panel of substrates to facilitate investigation of the full range of KDAC enzymes. The project will focus on establishing an efficient synthesis and performing rigorous in vitro evaluation of potential substrates.

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