Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 53, Issue 5, Pages 2063-2075Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm9015747
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research
Ask authors/readers for more resources
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and major targets for drug development. Herein, We Sought to identify the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding cleft that interact with all positions of the AngII using photoaffinity labeling. We conducted it complete iterative walk-through of the AngII sequence with either p-benzoyl-L-phenylalanine (Bpa) or p-[3-(trifluoromethyl)-3H-diazirin-3-yl]-L-phenylalanine (Tdf) to yield two series of eight photoreactive analogues. Pharmacological properties assessment of these sixteen analogues showed that the CAM receptor has it structure-activity relationship (SAR) more amenable to the amino acid Substitutions at Positions 1, 2, 3, and 5 of AngII than the WT receptor. Photoaffinity labeling of the CAM receptor with the selected analogues, which exhibit different but complementary photochemical properties, suggested that the AngII amino-terminus resides in a hydrophilic environment and interacts simultaneously with different regions of the hAT(1) receptor, including several ectodomains.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available