Thesis supervisor: Tamás Martinek
co-supervisor: Zsófia Hegedűs
Location of studies (in Hungarian): Universitat of Szeged, Faculty of Medicine Institute of Medical Chemistry Abbreviation of location of studies: OVI
Description of the research topic:
Protein-protein interactions (PPIs) play key role in cellular processes relevant to health and disease, inhibiting such interactions is a major challenge in chemical biology. The large, solvent exposed and shallow interaction interface of a PPI makes it difficult to target using conventional small drug molecules. An attractive alternative is the use of peptidomimetic ligands, but their optimization process is usually expensive and time-consuming. Techniques exploiting in vitro evolution (e.g. phage display) are powerful tools, but rely on ribosomal synthesis, thus cannot be used in case of non-natural building blocks. During this research we set out to investigate alternative methods that allow the iterative affinity maturation of non-natural peptidomimetic ligands and develop high affinity and selective PPI inhibitors. We employ dynamic combinatorial chemistry (DCC) approaches which allows the synthesis and selection of high affinity ligands in presence of a protein template. Alternatively, programmed assembly of ligand libraries on a DNA template results in compounds with their own genetic code, thus can be subjected to in vitro evolution cycles using the protein target as the selection pressure. We anticipate that these methods would facilitate the discovery of high affinity and selective peptidomimetic ligands targeting PPIs.
Required language skills: english Number of students who can be accepted: 1
Deadline for application: 2021-12-31
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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