Drug-Membrane Interactions in the Renin Angiotensin System

Allostery in membrane proteins

“…While it was believed that these binding sites are only accessible to endogenous ligands from the aqueous phase, recent work suggests that small molecules may access GPCRs by an indirect pathway through partitioning into the membrane and then reaching the binding site via lateral diffusion through the lipid bilayer. [28,29] Moreover, recent crystal structures reveal the existence of extrahelical lipid allosteric sites at the interface of the lipid--protein interface and at different bilayer depths. [28] Cholesterol and phospholipids can act as positive, negative allosteric and even orthosteric modulators of GPCRs by binding directly to receptor sites on the membrane interface or inside the receptor.…”

Interplay of cholesterol, membrane bilayers and the AT1R: A cholesterol consensus motif on AT1R is revealed

“…Candesartan cilexitil (Mw = 610.671 g/mol) was donated from CYPRIA Pharmaceutical Company and hydrolyzed to candesartan (Mw = 440.45 g/mol) by our lab according to the procedure published in Ref. [33] . DPPC (Mw = 734.039 g/mol)) was purchased from AvantiPolar Lipids Inc. (Alabaster, AL) and cholesterol from Sigma Aldrich (St Louis, USA).…”