phosphothreonine and 2-amino-4-phosphonobutyric-acid

Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)2-OH, 2] as a phosphatase-stable phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.

Topics: Aminobutyrates; Molecular Structure; Peptides; Phosphothreonine; Prodrugs; Solid-Phase Synthesis Techniques

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

Topics: Aminobutyrates; Animals; Evoked Potentials; Glutamates; Glutamic Acid; Hippocampus; Phosphoserine; Phosphothreonine; Rats; Receptors, Cell Surface; Receptors, Glutamate; Stereoisomerism; Structure-Activity Relationship; Synapses; Synaptic Transmission