ATTENTION/WARNING - NE PAS DÉPOSER ICI/DO NOT SUBMIT HERE

Ceci est la version de TEST de DIAL.mem. Veuillez ne pas soumettre votre mémoire sur ce site mais bien à l'URL suivante: 'https://thesis.dial.uclouvain.be'.
This is the TEST version of DIAL.mem. Please use the following URL to submit your master thesis: 'https://thesis.dial.uclouvain.be'.
 

Targeting the TSPYL5-USP7 interaction using nanobodies and peptides : a promising therapeutic strategy to target the alternative lengthening of telomeres (ALT) mechanism

Chakrowf, Joudy
(2024)

Files

CHAKROWF_08761800_2024.pdf
  • UCLouvain restricted access
  • Adobe PDF
  • 9.09 MB

Details

Supervisors
Frédérick, Raphaël
Faculty
Faculté de pharmacie et des sciences biomédicales
Degree label
Master [120] en sciences pharmaceutiques, à finalité approfondie
Abstract
Avoiding senescence is one of cancer hallmarks and can be achieve by telomeres maintenance mechanisms (TMM) activation. The Alternative lengthening of telomeres (ALT) is a TMM mostly activated in pediatric cancers and linked to cancers with a very poor prognosis. Therefore, it’s crucial to study this mechanism and find targets to treat ALT+ cells. Recently, the testis specific Y encoded like 5 (TSPYL5) was identified as a promising candidate to target ALT+ cells. TSPYL5 interacts with Ubiquitin specific protease 7 (USP7) leading to telomeres maintenance. Hence, our team opted to target this protein-protein interaction (PPI) by developing nanobodies and inhibitory peptides. In this master thesis, we employed biophysical methods to develop and optimize both strategies before conducting cellular assays. After a screening of nanobodies (Nbs), we selected one Nb that compete with the TSPYL5-USP7 interaction. We then proceeded to optimize the cellular assay to evaluate the potential of the inhibitory Nb. For the peptides strategy, our team performed a screening using peptides generated from the TSPYL5 amino acid sequence with the aim of identifying PPI hot-spots. Identifying hot-spots will help elucidate the 3D structure of TSPYL5. Furthermore, it will be used to develop inhibitory peptides. Overall, this master thesis brought us one step closer to developing effective cancer therapies.