Slack, Rachel D.; Abramyan, Ara M.; Tang, Helen; Meena, Sitaram; Davis, Bruce A.; Bonifazi, Alessandro; Giancola, JoLynn B.; Deschamps, Jeffrey R.; Naing, Sett; Yano, Hideaki; Singh, Satinder K.; Newman, Amy Hauck; Shi, Lei published the artcile< A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter>, HPLC of Formula: 3893-18-3, the main research area is serotonin transporter paroxetine serotonin reuptake inhibitors SAR asym chem; Paroxetine; asymmetric chemistry; organocatalysis; selective serotonin reuptake inhibitors; serotonin transporter; structure−activity relationship.
The serotonin transporter (SERT) is the primary target for the selective serotonin reuptake inhibitors (SSRIs). However, the structural basis for the extraordinarily high binding affinity of the widely prescribed SSRI, paroxetine, to human SERT (hSERT) has not yet been fully elucidated. Our previous findings unveiled a plausible ambiguity in paroxetine’s binding orientations that may constitute an integral component of this SSRI’s high affinity for hSERT. Herein, we investigate factors contributing to paroxetine’s high affinity by modifying both the ligand and the protein. We generated a series of bromine (Br)-containing derivatives and found that the one in which the 4-F of paroxetine had been replaced with the chem. similar but more electron-rich Br atom (13) had the highest affinity. By comparatively characterizing the binding of paroxetine and 13 to both wild type (WT) and a construct harboring a paroxetine-sensitive mutation in the binding cavity, we identified a mechanistic determinant responsible for the pose ambiguity of paroxetine, which can guide future drug design.
ACS Chemical Neuroscience published new progress about Binding energy (binding affinity). 3893-18-3 belongs to class bromides-buliding-blocks, and the molecular formula is C9H7BrO, HPLC of Formula: 3893-18-3.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary