Przemyslaw Grudnik

TL;DR: It is shown that these small-molecule compounds bind directly to PD-L1 and that they potently block PD-1 binding.

TL;DR: The latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies reveals that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies.

TL;DR: NMR and X-ray characterization is presented for the two classes of small-molecule PD-1/PD-L1 inhibitors that carry a number of disadvantages such as the high cost of the antibodies, their limited half-life, and immunogenicity.

TL;DR: Evidence is provided that small molecules are capable of alleviating the PD-1/PD-L1 immune checkpoint-mediated exhaustion of Jurkat T-lymphocytes and the X-ray structures of the complexes of B MS-1001 and BMS-1166 were determined, which revealed features that may be responsible for increased potency of the compounds compared to their predecessors.

TL;DR: This work presents an updated perception of the order of events in SRP-mediated protein targeting, in which the activation of GTP hydrolysis plays a key role for membrane insertion of substrate proteins.