Synthesis and receptor binding affinity of new selective GluR5 ligands
Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic g...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2001-04, Vol.9 (4), p.875-879 |
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| creator | Bunch, Lennart Johansen, Tina H. Bräuner-Osborne, Hans Stensbøl, Tine B. Johansen, Tommy N. Krogsgaard-Larsen, Povl Madsen, Ulf |
| description | Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid receptors. The (S)-enantiomers of E-4-(2,2-dimethylpropylidene)glutamic acid ((S)-1) and E-4-(3,3-dimethylbutylidene)glutamic acid ((S)-2) were shown to be selective and high affinity GluR5 ligands, with Ki values of 0.024 and 0.39μM, respectively, compared to Ki values at GluR2 of 3.0 and 2.0μM, respectively. Their affinities in the [3H]AMPA binding assay on native cortical receptors were shown to correlate with their GluR2 affinity rather than their GluR5 affinity. No affinity for GluR6 was detected (IC50>100μM).
(S)-1 and (S)-2 were synthesized and shown to be selective high affinity ligands at the glutamate receptor subtype GluR5, whereas only weak affinities were observed at GluR2. |
| doi_str_mv | 10.1016/S0968-0896(00)00304-7 |
| format | Article |
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(S)-1 and (S)-2 were synthesized and shown to be selective high affinity ligands at the glutamate receptor subtype GluR5, whereas only weak affinities were observed at GluR2.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/S0968-0896(00)00304-7</identifier><identifier>PMID: 11354670</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Biological and medical sciences ; Cell Line ; Chromatography, High Pressure Liquid ; Glutamatergic system (aspartate and other excitatory aminoacids) ; Glutamates - chemical synthesis ; Glutamates - pharmacology ; Humans ; Indicators and Reagents ; Ligands ; Magnetic Resonance Spectroscopy ; Medical sciences ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Receptors, AMPA - drug effects ; Receptors, Kainic Acid - drug effects ; Receptors, Kainic Acid - metabolism ; Tumor Cells, Cultured</subject><ispartof>Bioorganic & medicinal chemistry, 2001-04, Vol.9 (4), p.875-879</ispartof><rights>2001 Elsevier Science Ltd</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-e0ded4bb57a6c7c95b59c8ef1914df7131f8f1be7d963a51dd1e9949d5331d5e3</citedby><cites>FETCH-LOGICAL-c389t-e0ded4bb57a6c7c95b59c8ef1914df7131f8f1be7d963a51dd1e9949d5331d5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0968-0896(00)00304-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=967084$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11354670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bunch, Lennart</creatorcontrib><creatorcontrib>Johansen, Tina H.</creatorcontrib><creatorcontrib>Bräuner-Osborne, Hans</creatorcontrib><creatorcontrib>Stensbøl, Tine B.</creatorcontrib><creatorcontrib>Johansen, Tommy N.</creatorcontrib><creatorcontrib>Krogsgaard-Larsen, Povl</creatorcontrib><creatorcontrib>Madsen, Ulf</creatorcontrib><title>Synthesis and receptor binding affinity of new selective GluR5 ligands</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid receptors. The (S)-enantiomers of E-4-(2,2-dimethylpropylidene)glutamic acid ((S)-1) and E-4-(3,3-dimethylbutylidene)glutamic acid ((S)-2) were shown to be selective and high affinity GluR5 ligands, with Ki values of 0.024 and 0.39μM, respectively, compared to Ki values at GluR2 of 3.0 and 2.0μM, respectively. Their affinities in the [3H]AMPA binding assay on native cortical receptors were shown to correlate with their GluR2 affinity rather than their GluR5 affinity. No affinity for GluR6 was detected (IC50>100μM).
(S)-1 and (S)-2 were synthesized and shown to be selective high affinity ligands at the glutamate receptor subtype GluR5, whereas only weak affinities were observed at GluR2.</description><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>Glutamates - chemical synthesis</subject><subject>Glutamates - pharmacology</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Ligands</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, AMPA - drug effects</subject><subject>Receptors, Kainic Acid - drug effects</subject><subject>Receptors, Kainic Acid - metabolism</subject><subject>Tumor Cells, Cultured</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQQEVpSLbb_IQGQSG0B6czlWRbp1JC8wGBQD7OQpZGqYJX3krehP338WaX9JjTXN6bGR5jXxBOELD-cQu6bitodf0N4DuAAFk1H9gMZS0rITR-ZLM35IB9KuURAH5KjfvsAFEoWTcwY2e36zT-pRILt8nzTI6W45B5F5OP6YHbEGKK45oPgSd65oV6cmN8In7er24U7-PD5JXPbC_YvtDhbs7Z_dmfu9OL6ur6_PL091XlRKvHisCTl12nGlu7xmnVKe1aCqhR-tCgwNAG7KjxuhZWofdIWkvtlRDoFYk5O97uXebh34rKaBaxOOp7m2hYFdNAK1s5yXOmtqDLQymZglnmuLB5bRDMJqB5DWg2dQyAeQ1omsk72h1YdQvy_61dsQn4ugNscbYP2SYXyxun680LE_VrS9EU4ylSNsVFSo58nBKPxg_xnUdeAFYrjJw</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>Bunch, Lennart</creator><creator>Johansen, Tina H.</creator><creator>Bräuner-Osborne, Hans</creator><creator>Stensbøl, Tine B.</creator><creator>Johansen, Tommy N.</creator><creator>Krogsgaard-Larsen, Povl</creator><creator>Madsen, Ulf</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Synthesis and receptor binding affinity of new selective GluR5 ligands</title><author>Bunch, Lennart ; Johansen, Tina H. ; Bräuner-Osborne, Hans ; Stensbøl, Tine B. ; Johansen, Tommy N. ; Krogsgaard-Larsen, Povl ; Madsen, Ulf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-e0ded4bb57a6c7c95b59c8ef1914df7131f8f1be7d963a51dd1e9949d5331d5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>Glutamates - chemical synthesis</topic><topic>Glutamates - pharmacology</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Ligands</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, AMPA - drug effects</topic><topic>Receptors, Kainic Acid - drug effects</topic><topic>Receptors, Kainic Acid - metabolism</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bunch, Lennart</creatorcontrib><creatorcontrib>Johansen, Tina H.</creatorcontrib><creatorcontrib>Bräuner-Osborne, Hans</creatorcontrib><creatorcontrib>Stensbøl, Tine B.</creatorcontrib><creatorcontrib>Johansen, Tommy N.</creatorcontrib><creatorcontrib>Krogsgaard-Larsen, Povl</creatorcontrib><creatorcontrib>Madsen, Ulf</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bunch, Lennart</au><au>Johansen, Tina H.</au><au>Bräuner-Osborne, Hans</au><au>Stensbøl, Tine B.</au><au>Johansen, Tommy N.</au><au>Krogsgaard-Larsen, Povl</au><au>Madsen, Ulf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and receptor binding affinity of new selective GluR5 ligands</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>9</volume><issue>4</issue><spage>875</spage><epage>879</epage><pages>875-879</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid receptors. The (S)-enantiomers of E-4-(2,2-dimethylpropylidene)glutamic acid ((S)-1) and E-4-(3,3-dimethylbutylidene)glutamic acid ((S)-2) were shown to be selective and high affinity GluR5 ligands, with Ki values of 0.024 and 0.39μM, respectively, compared to Ki values at GluR2 of 3.0 and 2.0μM, respectively. Their affinities in the [3H]AMPA binding assay on native cortical receptors were shown to correlate with their GluR2 affinity rather than their GluR5 affinity. No affinity for GluR6 was detected (IC50>100μM).
(S)-1 and (S)-2 were synthesized and shown to be selective high affinity ligands at the glutamate receptor subtype GluR5, whereas only weak affinities were observed at GluR2.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>11354670</pmid><doi>10.1016/S0968-0896(00)00304-7</doi><tpages>5</tpages></addata></record> |
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| subjects | Biological and medical sciences Cell Line Chromatography, High Pressure Liquid Glutamatergic system (aspartate and other excitatory aminoacids) Glutamates - chemical synthesis Glutamates - pharmacology Humans Indicators and Reagents Ligands Magnetic Resonance Spectroscopy Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Receptors, AMPA - drug effects Receptors, Kainic Acid - drug effects Receptors, Kainic Acid - metabolism Tumor Cells, Cultured |
| title | Synthesis and receptor binding affinity of new selective GluR5 ligands |
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