Synthesis of a new kainic acid based selective ligand as a potential photoaffinity label of non-NMDA excitatory amino acid receptors in chicken brain.
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.
Sivvas
E
E
Department of Physiology, Medical School, University of Patras, Greece.
Voukelatou
G
G
Kouvelas
E D
ED
Francis
G W
GW
Aksnes
D W
DW
Papaioannou
D
D
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
C086289:4-(1-(4-azidobenzamidomethyl)ethenyl)-2-carboxypyrrolidin-3-ylacetic acid; D000345:Affinity Labels; D001386:Azides; D017459:Receptors, Amino Acid; D007608:Kainic Acid