Interaction of telmisartan and related sartans with the programmed cell death-ligand 1 (PD-L1) protein dimer: a molecular docking analysis

Interaction of telmisartan and related sartans with the programmed cell death-ligand 1 (PD-L1) protein dimer: a molecular docking analysis

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Abstract Background Telmisartan (TLT) is a prototypic angiotensin receptor blocker largely used to treat hypertension worldwide.In addition to its cardioprotective effects, TLT presents pleiotropic activities and notably displays noticeable anti-inflammatory and antitumor effects.The repression of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint may be implicated antitumor action of TLT, as it is the case with many other compounds equipped with a biphenyl moiety.

We have used molecular modeling to compare the interaction of TLT and derivatives with the PD-L1 dimer protein.Results Two molecules, TLT-dimer and TLT-acylglucuronide, were found to form more stable complexes with VITAMIN K/A/D3 LIQUID PD-L1 than TLT itself.In parallel, the docking analysis performed with a series of 12 sartans led to the identification of Olmesartan as a potential PD-L1 binder.

The stacked biphenyl unit of Olmesartan positions the molecule along the groove delimited by the two protein monomers.The flanking tetrazole and imidazole moieties, on each side ANTI-HUM HAIR SPRAY of the biphenyl unit of Olmesartan, contribute favorably to the protein interaction via specific hydrogen bonding interactions.Conclusions The computational analysis suggests a possible binding of Olmesartan to PD-L1 dimer and thus offers novel perspectives for the design of small molecules capable of interrupting the PD-1/PD-L1 immune checkpoint.

Experimental studies are warranted to validate the hypothesis.Graphical abstract.