Biotechnological evaluation of heterochiral cyclic peptides as inhibitors of PD-1/PD-L1 interaction

Identifier:  TFG:3022

Handle: https://hdl.handle.net/20.500.11797/TFG3022

Authors:  Roig Soriano, Xavier

Abstract:
Programmed cell death protein 1 (PD-1) is a receptor found on the cytoplasmic membrane of cells of the immune system (IS). Cells interact with PD-1 through their natural ligand, PD-L1. With this interaction the immune system recognizes healthy cells and inhibits its action against them. If this interaction does not occur, it will trigger the response to eliminate them. In some types of cancer, has been detected an increased expression of PD-L1 simulating a healthy cell, as a cancer adaptation mechanism to escape the immune response. This project focuses on evaluating peptides that can block this interaction. In this way, it would prevent cancer cells from being perceived as healthy cells and, therefore, the immune system could attack tumour proliferation. The anti-PD-1 peptides have been evaluated by three different biophysical techniques: Microscale Thermophoresis (MST), Isothermal Titration Calorimetry (ITC) and Nuclear Magnetic Resonance (NMR). Among all the peptides tested, PD-i3, PD-i5 and PD-i6 stood out, which presented affinity values of the order of the natural ligand and, therefore, can compete to inhibit endogenous interaction. The zone of interaction with these peptides on PD-1 surface was also verified by NMR. Consequently, these peptides are promising candidates for interfering with the PD-1 / PD-L1 interaction and, with this, achieve an immune response against.