Abstract
DL-threo-beta-benzyloxyaspartate (DL-TBOA) is a non-transportable blocker of the glutamate transporters that serves as an indispensable tool for the investigation of the physiological roles of the transporters. To examine the precise interaction between a blocker and the transporters, we synthesized the optically pure isomers (L- and D-TBOA) and its erythro-isomers. L-TBOA is the most potent blocker for the human excitatory amino acid transporters (EAAT1-3), while D-TBOA revealed a difference in the pharmacophores between EAAT1 and EAAT3. We also synthesized the substituent variants (methyl or naphthylmethyl derivatives) of L-TBOA. The results obtained here suggest that bulky substituents are crucial for non-transportable blockers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / antagonists & inhibitors*
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ATP-Binding Cassette Transporters / metabolism
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Amino Acid Transport System X-AG
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Animals
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / chemical synthesis*
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Aspartic Acid / chemistry
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Aspartic Acid / pharmacology*
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Biological Transport / drug effects
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CHO Cells
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COS Cells
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Cricetinae
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Glutamic Acid / metabolism*
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Humans
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Kinetics
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Models, Molecular
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Molecular Structure
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Patch-Clamp Techniques
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Rats
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Receptors, Glutamate / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
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Transfection
Substances
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ATP-Binding Cassette Transporters
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Amino Acid Transport System X-AG
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Receptors, Glutamate
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benzyloxyaspartate
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Aspartic Acid
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Glutamic Acid