Chemical Biology

Chemical Biology

Prof. Dr. Markus Kaiser


Prof. Dr. Markus Kaiser

Faculty of Biology
Center of Medical Biotechnology (ZMB)
University of Duisburg-Essen

Research Overview

The Kaiser group develops and uses chemical biology approaches to investigate diverse aspects of regulated proteolysis and to study the molecular mechanisms behind bioactive small molecule action. Our interests are however not limited to basic research; rather, we aim to capitalize on our scientific findings for drug discovery or other medicinal applications.

Selected Publications

Merdanovic M, Burston SG, Schmitz AL, Köcher S, Knapp S, Clausen T, Kaiser M, Huber R, Ehrmann M. Activation by substoichiometric inhibition. Proc Natl Acad Sci U S A. 2020 Jan 6;201918721.

Weith M, Seiler J, van den Boom J, Kracht M, Hülsmann J, Primorac I, Del Pino Garcia J, Kaschani F, Kaiser M, Musacchio A, Bollen M, Meyer H. Ubiquitin- Independent Disassembly by a p97 AAA-ATPase Complex Drives PP1 Holoenzyme Formation. Mol Cell . 2018 Nov 15;72(4):766-777.e6.

Ziemann S, van der Linde K, Lahrmann U, Acar B, Kaschani F, Colby T, Kaiser M, Ding Y, Schmelz E, Huffaker A, Holton N, Zipfel C, Doehlemann G. An apoplastic peptide activates salicylic acid signalling in maize. Nat Plants. 2018 Mar;4(3):172-180.

Pöhler R, Krahn JH, van den Boom J, Dobrynin G, Kaschani F, Eggenweiler HM, Zenke FT, Kaiser M, Meyer H. A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases. Angew Chem Int Ed Engl. 2018 Feb 5;57(6):1576-1580.

Köcher S, Rey J, Bongard J, Tiaden AN, Meltzer M, Richards PJ, Ehrmann M, Kaiser M. Tailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease Inhibitors. Angew Chem Int Ed Engl. 2017 Jul 10;56(29):8555-8558.

Zweerink S, Kallnik V, Ninck S, Nickel S, Verheyen J, Blum M, Wagner A, Feldmann I, Sickmann A, Albers SV, Bräsen C, Kaschani F, Siebers B, Kaiser M. Activity-based protein profiling as a robust method for enzyme identification and screening in extremophilic Archaea. Nat Commun. 2017 May 8;8:15352.

Zweerink S, Pollmann T, Ninck S, Kaschani F, Kaiser M. Activity-Based Protein Profiling with Natural Product-Derived Chemical Probes in Human Cell Lysates. Methods Mol Biol. 2017;1491:23-46.

van den Boom J, Wolf M, Weimann L, Schulze N, Li F, Kaschani F, Riemer A, Zierhut C, Kaiser M, Iliakis G, Funabiki H, Meyer H. VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair. Mol Cell. 2016 Oct 6;64(1):189-198.

Poepsel S, Sprengel A, Sacca B, Kaschani F, Kaiser M, Gatsogiannis C, Raunser S, Clausen T, Ehrmann M. Determinants of amyloid fibril degradation by the PDZ protease HTRA1.
Nat Chem Biol. 2015 Nov;11(11):862-9.

Meesters C, Mönig T, Oeljeklaus J, Krahn D, Westfall CS, Hause B, Jez JM, Kaiser M, Kombrink E. A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana. Nat Chem Biol. 2014 Oct;10(10):830-6.

Oeljeklaus J, Kaschani F, Kaiser M. Streamlining chemical probe discovery: libraries of "fully functionalized" small molecules for phenotypic screening. Angew Chem Int Ed Engl. 2013 Jan 28;52(5):1368-70.

Stein ML, Beck P, Kaiser M, Dudler R, Becker CF, Groll M. One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18367-71.

Kaschani F, Clerc J, Krahn D, Bier D, Hong TN, Ottmann C, Niessen S, Colby T, van der Hoorn RA, Kaiser M. Identification of a selective, activity-based probe for glyceraldehyde 3-phosphate dehydrogenases. Angew Chem Int Ed Engl. 2012 May 21;51(21):5230-3.

Ottmann C, van der Hoorn RA, Kaiser M. The impact of plant-pathogen studies on medicinal drug discovery. Chem Soc Rev. 2012 Apr 21;41(8):3168-78.

Thiel P, Kaiser M, Ottmann C. Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery? Angew Chem Int Ed Engl. 2012 Feb 27;51(9):2012-8.

Krahn D, Ottmann C, Kaiser M. The chemistry and biology of syringolins, glidobactins and cepafungins (syrbactins). Nat Prod Rep. 2011 Oct;28(11):1854-67.

Merdanovic M, Clausen T, Kaiser M, Huber R, Ehrmann M. Protein quality control in the bacterial periplasm. Annu Rev Microbiol. 2011;65:149-68.

Clausen T, Kaiser M, Huber R and M. Ehrmann. HtrA proteases: Regulated proteolysis in protein quality control. Nat Rev Mol Cell Biol. 2011 Mar;12(3):152-62.

Truebestein L, Tennstaedt A, Mönig T, Krojer T, Canellas F, Kaiser M, Clausen T, Ehrmann M. Substrate-induced remodeling of the active site regulates human HTRA1 activity. Nat Struct Mol Biol. 2011 Mar;18(3):386-8.

Merdanovic M, Mamant N, Meltzer M, Poepsel S, Auckenthaler A, Melgaard R, Hauske P, Nagel-Steger L, Clarke AR, Kaiser M, Huber R, and M. Ehrmann. (2010) Determinants of structural and functional plasticity of a widely conserved protease chaperone complex. Nat. Struct. Mol. Biol. 17:837-43.

Wetzel S, Wilk W, Chammaa S, Sperl B, Roth AG, Yektaoglu A, Renner S, Berg T, Arenz C, Giannis A, Oprea TI, Rauh D, Kaiser M, Waldmann H. A scaffold-tree- merging strategy for prospective bioactivity annotation of gamma-pyrones. Angew Chem Int Ed Engl. 2010 May 10;49(21):3666-70.

Ottmann C, Rose R, Huttenlocher F, Cedzich A, Hauske P, Kaiser M, Huber R, Schaller A. Structural basis for Ca2+-independence and activation by homodimerization of tomato subtilase 3. Version 2. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17223-8.

Knoth T, Warburg K, Katzka C, Rai A, Wolf A, Brockmeyer A, Janning P, Reubold TF, Eschenburg S, Manstein DJ, Hübel K, Kaiser M, Waldmann H. The Ras pathway modulator melophlin A targets dynamins. Angew Chem Int Ed Engl. 2009;48(39):7240-5.

Clerc J, Groll M, Illich DJ, Bachmann AS, Huber R, Schellenberg B, Dudler R, Kaiser M. Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition. Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6507-12.

Wang Z, Gu C, Colby T, Shindo T, Balamurugan R, Waldmann H, Kaiser M, van der Hoorn RA. Beta-lactone probes identify a papain-like peptide ligase in Arabidopsis thaliana. Nat Chem Biol. 2008 Sep;4(9):557-63.

Nören-Müller A, Wilk W, Saxena K, Schwalbe H, Kaiser M*, Waldmann H*. Discovery of a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B by biology-oriented synthesis. Angew Chem Int Ed Engl. 2008;47(32):5973-7.
* cor-responding authors. Flagged as an Hot article.

Groll M, Schellenberg B, Bachmann AS*, Archer CR, Huber R, Powell TK, Lindow S, Kaiser M*, Dudler R*. A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism. Nature. 2008 Apr 10;452(7188):755-8.
* corresponding authors.
Highlighted in Chem. Eng. News 2008, 86, 39; Chem. Biol. 2008, 15, 419-421.

Meltzer M, Hasenbein S, Hauske P, Kucz N, Merdanovic M, Grau S, Beil A, Jones D, Krojer T, Clausen T, Ehrmann M,* and M. Kaiser* (2008). Allosteric activation of HtrA protease DegP by stress signals in bacterial protein quality control. Angew Chem. Int. Ed. Engl. 47:1332-1334 *corresponding authors.

Kaiser M, Groll M, Renner C, Huber R, Moroder L. The core structure of TMC-95A is a promising lead for reversible proteasome inhibition. Angew Chem Int Ed Engl. 2002 Mar 1;41(5):780-3.
Chem. Int. Ed. 2002, 41, 780-783. Highlighted in Chem. Eng. News 2002, 80, 14.

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Research Projects

European Regional Development Fund
(Europäischer Fonds für regionale Entwicklung)
EFRE Project

Inhibitors of the serin protease HTRA1 for the treatment of age-related blindness (2018-2022)

Participating Institutions
Lead Discovery Center GmbH Dortmund
University of Duisburg-Essen

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