Photoactivatable ligand tools for CXCR4 and ACKR3

Early stage researcher 1 (ESR1) project
Supervision: Prof. Dr. Rob Leurs, Prof. Dr. Iwan de Esch, Dr. Maikel Wijtmans
Host: Vrije Universiteit Amsterdam

I- Project proposal:

Aim:
The project aims for the design, synthesis and photochemistry of novel photoswitchable ligands for the CXCR4 and ACKR3 chemokine receptors.

Methodology:
This project will entail the design, synthesis and photochemical characterization of photoswitchable small-molecule CXCR4 and ACKR3 ligands. A wide variety of chemical transformations, synthetic equipment and photochemical techniques will be employed to generate and analyze the ligands. The design of any new ligands can be supported by computer-aided drug design studies where necessary. In vitro and in vivo pharmacological assays on the ligands will be conducted by fellow ESR7.

Planned secondments:

Heptares – the candidate will use modelling for characterizing the binding site of developed tools in CXCR4 X-ray structure and ACKR3 models.

University Hospital Jena – the candidate will work on in vitro characterization of photoswitchable compounds using single cell microscopy methodology.

II – Requirement candidate:

Required diploma: A MSc degree in Chemistry (or related field) with a specialization in Synthetic Organic Chemistry and/or Synthetic Medicinal Chemistry.

Required expertise: Experience in the design and synthesis of biologically active compounds is a necessity. The candidate has a strong background (theoretical and practical) in synthetic organic chemistry or synthetic medicinal chemistry.

Recommended expertise: Expertise in photochemistry is a strong pre. Expertise in medicinal chemistry on GPCRs is a pre.

Key publications:

Hauwert et al., J. Am. Chem. Soc. 2018, 140, 4232
Hauwert et al., Angew. Chem. Intl. Ed. 2019, 58, 4531
Gómez-Santacana et al., Angew. Chem. Intl. Ed. 2018, 57, 11608
Gómez-Santacana et al., Beilstein Arch. 2019, doi:10.3762/bxiv.2019.69.v1