A novel hydrophobic tag leads to the efficient degradation of programmed death-ligand 1.

ABSTRACT: The interaction of PD-L1 and PD-1 transmits the inhibitory signal to reduce the proliferation of antigen-specific T-cells in lymph nodes. The expression of PD-L1 confers a potential escaping mechanism of tumors from the host immune system. Blocking the interaction of PD-1 and PD-L1 enables tumor-reactive T cells to overcome regulatory mechanisms and induce an effective antitumor response. The hydrophobic tag tethering degrader (HyTTD) contains a hydrophobic moiety, binding to the protein of interest (POI) to mimic the misfolding state of the POI, thereby inducing the degradation of POI. In this work, using the HyTTD strategy, we selected the diphenylmethyl derivatives as the PD-L1 binding motif for PD-L1 to develop the degraders for PD-L1, and multiple hydrophobic tags were attached. As a

SUBMITTER: Gao J 

PROVIDER: S-EPMC11411611 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature