title: Synthesis of a new kainic acid based selective ligand as a potential photoaffinity label of non-NMDA excitatory amino acid receptors in chicken brain.
abstract: The synthesis of two analogues of kainic acid (KA) incorporating photo-activatible moieties attached either on the gamma-carboxy function (gamma-amide 1) or the isopropenyl side-chain (amide 2) is described. The synthesis of the former amide involves coupling of N-(tert-butoxycarbonyl)-protected alpha-diphenylmethyl kainate with 2-(4-azidobenzamido)ethylamine (5) followed by trifluoroacetic acid mediated complete deprotection. Amide 2 was synthesized by palladium-mediated allylic amination, with 4,4'-dimethoxybenzhydrylamine (DMBA), of N-(9-fluorenylmethoxycarbonyl)-protected dimethyl kainate, followed by splitting the DMB-group with formic acid, coupling with N-hydroxysuccinimidoyl 4-azidobenzoate and finally complete deprotection by saponification. Preliminary pharmacological studies in chicken brain membranes showed that amide 2 is a stronger inhibitor of [3H]KA binding on chicken cerebellar membranes than is amide 1 and that amide 2 has specificity only for the cerebellar, as opposed to the telencephalon, type of non-NMDA binding sites.
authors.affiliation: Department of Physiology, Medical School, University of Patras, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Sivvas
authors.forename: G
authors.initials: G
authors.lastname: Voukelatou
authors.forename: E D
authors.initials: ED
authors.lastname: Kouvelas
authors.forename: G W
authors.initials: GW
authors.lastname: Francis
authors.forename: D W
authors.initials: DW
authors.lastname: Aksnes
authors.forename: D
authors.initials: D
authors.lastname: Papaioannou
mesh_terms: D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002645:Chickens; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D015394:Molecular Structure; D010777:Photochemistry; D017459:Receptors, Amino Acid / Q000378:metabolism*; D013687:Telencephalon / Q000378:metabolism
chemical_list: C086289:4-(1-(4-azidobenzamidomethyl)ethenyl)-2-carboxypyrrolidin-3-ylacetic acid; D000345:Affinity Labels; D001386:Azides; D017459:Receptors, Amino Acid; D007608:Kainic Acid