Elma Mons


My background is in organic synthesis, with a strong affinity for molecules with a biological application. Inhibitors are effective as long as they are bound to the protein target, and irreversible inhibitors do not dissociate from their target, resulting in a  prolonged therapeutic effect after clearance from the blood, until de novo protein synthesis. Most of the existing targeted irreversible covalent inhibitors contain a reactive group (warhead, or electrophile) that has the ability to form a covalent bond to a cysteine residue in their protein target. However, the ability to form a covalent adduct with thiols has been linked to an increased risk of idiosyncratic toxicity. My PhD research involves chemical modification of the electrophile in existing irreversible inhibitors to prevent indiscriminate modification of non-targeted thiols, thereby improving the safety of irreversible inhibitors. My current work focusses on evaluation of inhibitory activity and binding mode on recombinant cysteine proteases, and analysis of cysteine protease labeling in cell lysates by activity-based probes with modified warheads.

Curriculum Vitae:

I obtained my Masters’ degree in Chemistry (Molecular Design, Synthesis and Catalysis) at the University of Amsterdam. My first internship was in the group of Prof. Dr. Henk Hiemstra (UvA), where I worked on methodology for the enantioselective, organocatalytic synthesis of tetrahydroisoquinolines. For my final master thesis I went to the group of Prof. Dr. Karl Gademann at the University of Basel in Switserland, to work on the semisynthesis of natural product derivatives for mode of action studies. I started my PhD research in the Ovaa group in 2014 to work on the design and synthesis of warheads for covalent enzyme inhibition, and their incorporation in small molecule inhibitors and probes.


  • Organocatalytic enantioselective Pictet-Spengler reactions for the syntheses of 1-substituted 1,2,3,4-tetrahydroisoquinolines.

    Mons, E; Wanner, M.J.; Ingemann, S.; van Maarseveen, J.H.; Hiemstra, H.;

    J. Org. Chem. 2014. doi: 10.1021/jo501099h.

  • The Alkyne Moiety as a Latent Electrophile in Irreversible Covalent Small Molecule Inhibitors of Cathepsin K

    Mons, E.; Jansen, I.D.C.; Loboda, J.; van Doodewaerd, B.R.; Hermans, J.; Verdoes, M.; van Boeckel, C.A.A.; van Veelen, P.A.; Turk, B.; Turk, D.; Ovaa, H.;

    J. Am. Chem. Soc. 2019, 141 (8), pp 3507–3514. doi: 10.1021/jacs.8b11027


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