A Selective Photoaffinity Ligand for the Kainate Class of Excitatory Amino Acid Receptor

Dean A. Wacker; Frank E. Lovering; Richard J. Bridges; Colin Willis; Richard Bartlett; A. Richard Chamberlin

doi:10.1055/s-1997-6129

Synlett 1997; 1997(SI): 503-504
DOI: 10.1055/s-1997-6129

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A Selective Photoaffinity Ligand for the Kainate Class of Excitatory Amino Acid Receptor

Dean A. Wacker¹ , Frank E. Lovering¹ , Richard J. Bridges² , Colin Willis² , Richard Bartlett² , A. Richard Chamberlin¹

¹Department of Chemistry, University of California, Irvine, CA 92717
²Department of Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, U.S.A.

Abstract

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The isopropenyl side chain of kainic acid (KA) has been replaced with a trifluoromethyldiazoketone group, resulting in a derivative ("diazoKA") that gives efficient photo-induced crosslinking to the active site of the KA class of glutamate receptor. The incorporation of this functional group is accomplished via a simple, one step coupling of a carboxylic acid and 2,2,2-trifluorodiazoethane in a procedure that should be generally applicable to the preparation of other photoaffinity labels. Major advantages include excellent stability towards acidic conditions, even Boc and t-butyl ester deprotection, as well as a reduced tendency to undergo (non-productive) Wolff rearrangement after binding and irradiation. The observed crosslinking paves the way for identifying the active site residues of the KA receptor.

kainic acid - trifluoromethyldiazoketone - photoaffinity ligand - trifluoromethyldiazomethane coupling - KA receptor

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