Inhibition of the Vesicular Glutamate Transporter (VGLUT) with Congo Red Analogs: New Binding Insights.

ABSTRACT: The vesicular glutamate transporter (VGLUT) facilitates the uptake of glutamate (Glu) into neuronal vesicles. VGLUT has not yet been fully characterized pharmacologically but a body of work established that certain azo-dyes bearing two Glu isosteres via a linker were potent inhibitors. However, the distance between the isostere groups that convey potent inhibition has not been delineated. This report describes the synthesis and pharmacologic assessment of Congo Red analogs that contain one or two glutamate isostere or mimic groups; the latter varied in the interatomic distance and spacer properties to probe strategic binding interactions within VGLUT. The more potent inhibitors had two glutamate isosteres symmetrically linked to a central aromatic group and showed IC₅₀ values ~ 

SUBMITTER: Hitt DM 

PROVIDER: S-EPMC7904594 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature