ESR Application form

ESR 11: Design, synthesis and evaluation of phosphinic transition-state analogues of ERAP/IRAP

Recruiting Institution: National and Kapodistrian University of Athens, GR PhD institution: National and Kapodistrian University of Athens, GR	Supervisor: Prof. Dimitris Georgiadis
Project Description The modulation of antigen processing mediated by ERAPs/IRAP relies on the development of chemical tools that will be able to potently and selectively target these enzymes. Such tools may provide enormous possibilities in the study of pathophysiology of ERAPs/IRAP and serve as valuable leads for the discovery of drug-like molecules for therapeutic applications. Phosphinic pseudopeptides constitute a class of compounds that act as transition-state analogue inhibitors of Zn-metalloproteases. This project involves the development (synthesis, purification and characterization) of phosphinic pseudopeptidic inhibitors of ERAPs/IRAP by using combinatorial and late-stage diversification techniques in order to identify crucial structure-activity relationships that will reveal unknown selectivity patterns. In addition, activity-based probes of different technologies will be synthesized and evaluated, based on the molecular scaffold of known inhibitors as well as new, selective inhibitors that will be identified during the project. The ESR will work in the Laboratory of Organic Chemistry of the Chemistry Department, NKUA. The Chemistry Department is located at the University Campus and is fully-equipped to serve the purposes of research project’s successful implementation. Core infrastructure facilities include a 400MHz and 200 ΜΗz NMR instrument, UV, IR, LC-MS, GC-MS, HRMS spectrometers, HPLC systems and microwave reactors. The ESR will join the research group of Prof D. Georgiadis working in an environment with long experience in synthetic medicinal chemistry and drug discovery.
Essential Background: Experience in Synthetic Organic Chemistry and/or Synthetic Medicinal Chemistry; Experience in Organic Laboratory Techniques	Desirable Background: Experience in Biochemistry ; Experience in Peptide Chemistry
Local Requirements: Bachelor Degree in Chemistry , Master Degree or Equivalent, in the Field of Organic Chemistry or Synthetic Medicinal Chemistry
Planned Secondments: Academic to University of Lille (FR) 2M, for ADMET characterisation techniques; Industrial secondment to Edelris (Lyon, FR) 2M, for drug design and medicinal chemistry techniques.
Planned Starting Date: 1^st Oct. 2021	Application Deadline 15^th May 2021