ESR3: Warhead Library of Covalent Fragment Binders

Host: RCNS, Hungary (PhD enrolment at Budapest University of Technology and Economics)
Academic supervisor: Prof. dr. György M. Keserű (RCNS)
Researcher: Aaron Keeley

Download the full description of this project: ESR3: Warhead Library of Covalent Fragment Binders

The starting points of FBLD studies are highly curated collections of small, chemically diverse and highly soluble fragments. To increase the diversity of the available fragment libraries, ESR3 will design and synthesise a reactive ‘warhead’ library and establish techniques for screening covalent binders against several FragNet protein targets, including kinases.

Designing and creating a compound library of fragment sized molecules with reactive warheads: “warhead library”. 2. Establishing techniques for efficient detection of covalent binders in a screening setup. 3. Screening of “warhead” library and virtual hits identified by ESR9 against various protein targets, e.g., Janus kinases. 4. Extending covalent binders into lead-­‐like compounds.

By using synthetic organic chemistry, computational chemistry and (structure-­‐based) drug design, a general fragment library for screening of covalent ligands will be created. The identification of covalent inhibitors for therapeutically relevant proteins, including Janus kinases, will be explored.

Preparative organic chemistry or theoretical organic chemistry or chemical biology knowledge and lab experience, analytical or bioanalytical background will be beneficial.

Key publications
1. Jöst et al. J. Med. Chem. 2014, 57, 7590-7599
2. Mark et al. J. Med. Chem. 2014, 57, 10072-10079
3. Baskin et al. PLoS ONE 2014, 9(8), e105568.

Other projects:

Contact details

Please contact us at:

FRAGNET Coordinator
VU University Amsterdam
The Netherlands

Funded by

Marie Curie Actions

EU Horizon 2020

European Union