Claff, Tobias published the artcileSingle Stabilizing Point Mutation Enables High-Resolution Co-Crystal Structures of the Adenosine A2A Receptor with Preladenant Conjugates, Computed Properties of 377727-87-2, the publication is Angewandte Chemie, International Edition (2022), 61(22), e202115545, database is CAplus and MEDLINE.
The G protein-coupled adenosine A2A receptor (A2AAR) is an important new (potential) drug target in immuno-oncol., and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A2AAR have been solved, mostly using the A2A-StaR2 protein that bears 9 point mutations, co-crystallization with Preladenant derivatives has so far been elusive. We developed a new A2AAR construct harboring a single point mutation (S913.39K) which renders it extremely thermostable. This allowed the co-crystallization of two novel Preladenant derivatives, the polyethylene glycol-conjugated (PEGylated) PSB-2113, and the fluorophore-labeled PSB-2115. The obtained crystal structures (2.25 S and 2.6 S resolution) provide explanations for the high potency and selectivity of Preladenant derivatives They represent the first crystal structures of a GPCR in complex with PEG- and fluorophore-conjugated ligands. The applied strategy is predicted to be applicable to further class A GPCRs.
Angewandte Chemie, International Edition published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Computed Properties of 377727-87-2.
Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics