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Modifying AMPA to increase Glutamate Receptor Ligand-Binding. (Chemistry Paper Abstracts).

Matthew J. Grieser*

2-Amino-3-(3-carboxyl-5-methyl-4-isoxazoyl) propionic acid (ACPA) was modified by double activation at the three position with amino alcohols using SmCl3 and N-Butyl Lithium. These molecules were Snthesized for Glutamate Receptor Ligand-Binding studies to test the bulk tolerance, pKa, and chiral interactions at the T655 binding site. The AMPA neurotransmitter receptor is an integral component of the human central nervous system that aids functions of eyesight, memory, and synapse growth. Dysfunction has been related to cerebral vascular accidents (CVA) as well as Alzheimer's, Parkinson's, Huntington's, and other neurological disorders. Based on Gouaux's crystal structure of the Glutamate receptor binding domain using Kainate, we used a rational structural-based design to develop AMPA analogues that we postulate will posses a higher binding affinity for the Glutamate receptor (1).

(1.) Armstrong, N.; Sun, Y,; Chen, G.; Gouaux, E.; Nature, 1998, 395, 913-917.

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Title Annotation:amino propionic acid
Author:Grieser, Matthew J.; Burkhart, David J.; Natale, N.R.
Publication:Journal of the Idaho Academy of Science
Article Type:Brief Article
Geographic Code:1USA
Date:Jun 1, 2001
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