Structure-activity relationships of l-glutamate receptor ligands: Role of the ω-acidic terminal☆

Abstract Acidic amino acid analogues varying in their ω-terminal were evaluated: (1) as neuronal excitants or antagonists of excitatory synaptic transmission, and (2) as inhibitors of l -[ 3 H]glutamate binding to synaptic membranes. ω-Phosphonates were antagonists and inhibited l -glutamate binding to the 2-amino-4-phosphonobutyrate (APB)-sensitive population of binding sites; ω-sulfonates and ω-carboxylates were excitants and inhibited l -glutamate binding to APB-sensitive and -insensitive sites. The data indicate that properties of the ω-acidic group are important for establishing the relative potencies of antagonist substances and the overall excitatory/antagonist activity of these analogues.