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Custom Vector Construction> | The HA-tagged hBGT1 Y453S, Y453A, Y453S + Y454A, and hGAT3 S468Y constructs were obtained from GenScript (Piscataway, NJ, USA). | Get A Quote |
: N-(1-Benzyl-4-piperidinyl)-2,4-dichlorobenzamide 5 (BPDBA) is a noncompetitive inhibitor of the betaine/GABA transporter 1 (BGT1). We here report the synthesis and structure−activity relationship of 71 analogues. We identify 26m as a more soluble 2,4-Cl substituted 3- pyridine analogue with retained BGT1 activity and an improved off-target profile compared to 5. We performed radioligand-based uptake studies at chimeric constructs between BGT1 and GAT3, experiments with site-directed mutated transporters, and computational docking in a BGT1 homology model based on the newly determined X-ray crystal structure of the human serotonin transporter (hSERT). On the basis of these experiments, we propose a binding m... More