{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360574096473290752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/tcr.20145"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Ftcr.20145"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/tcr.20145"}}],"dc:title":[{"@value":"Glutamate transporter blockers for elucidation of the function of excitatory neurotransmission systems"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p><jats:sc>L</jats:sc>‐Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Termination of glutamate receptor activation and maintenance of low extracellular glutamate concentrations are mainly achieved by glutamate transporters [excitatory amino acid transporters 1–5 (EAAT1–5)] located in nerve endings and surrounding glial cells. Selective and potent inhibitors have long been required to investigate the physiological significance of transporters in the regulation of synaptic transmission and the pathogenesis of neurological diseases. Non‐transportable blockers are desirable because, unlike competitive substrates, they do not cause ion flux and heteroexchange. After a series of possible candidate molecules, we synthesized<jats:italic>threo</jats:italic>‐β‐benzyloxyaspartate (TBOA), the first non‐transportable blocker for all subtypes of EAATs. In addition, TBOA analogs with a bulky substituent on their benzene ring showed enhanced inhibition of labeled glutamate uptake. Comparing the effects of substrates and non‐transportable blockers revealed the physiological roles of EAATs. We also developed a novel binding assay system using a tritium‐labeled TBOA analog. In this review, we describe the design and synthesis of these blockers and the functions of the EAATs elucidated with them. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 182–199; 2008: Published online in Wiley InterScience (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://www.interscience.wiley.com\">www.interscience.wiley.com</jats:ext-link>) DOI 10.1002/tcr.20145</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380574096473290752","@type":"Researcher","foaf:name":[{"@value":"Keiko Shimamoto"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"15278999"},{"@type":"EISSN","@value":"15280691"}],"prism:publicationName":[{"@value":"The Chemical Record"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2008-01","prism:volume":"8","prism:number":"3","prism:startingPage":"182","prism:endingPage":"199"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Ftcr.20145"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/tcr.20145"}],"createdAt":"2008-06-18","modifiedAt":"2025-01-30","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004229990117632","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Kinetic Resolution and Stereoselective Synthesis of 3‐Substituted Aspartic Acids by Using Engineered Methylaspartate Ammonia Lyases"}]},{"@id":"https://cir.nii.ac.jp/crid/1360005516846483584","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Functional roles of the glial glutamate transporter (GLAST) in emotional and cognitive abnormalities of mice after repeated phencyclidine administration"}]},{"@id":"https://cir.nii.ac.jp/crid/1521417754931742592","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Award Accounts : The Chemical Society of Japan Award for Creative Work for 2013 : Elucidation of Excitatory Neurotransmission and Membrane Protein Integration Mechanisms"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1002/tcr.20145"},{"@type":"CROSSREF","@value":"10.1002/chem.201301832_references_DOI_C0LTtFML2qELNG1CHLC1soy6ind"},{"@type":"CROSSREF","@value":"10.1246/bcsj.20150336_references_DOI_C0LTtFML2qELNG1CHLC1soy6ind"},{"@type":"CROSSREF","@value":"10.1016/j.euroneuro.2019.06.005_references_DOI_C0LTtFML2qELNG1CHLC1soy6ind"}]}