conantokin-t and Seizures

Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. The amino acid sequence of the peptide was determined and verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, gamma-carboxyglutamate (Gla). The sequence of the peptide is: Gly-Glu-Gla-Gla-Tyr-Gln-Lys-Met-Leu-Gla-Asn-Leu-Arg-Gla-Ala-Glu-Val-Lys- Lys-Asn-Ala-NH2. Conantokin-T inhibits N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. This observation suggests that like conantokin-G (a homologous Conus peptide with recently identified NMDA antagonist activity) conantokin-T has NMDA antagonist activity. A sequence comparison of conantokins-T and -G identifies the 4 Gla residues and the N-terminal dipeptide sequence as potential key elements for the biological activity of this peptide.

Topics: 1-Carboxyglutamic Acid; Amino Acid Sequence; Animals; Aspartic Acid; Benzofurans; Calcium; Cerebellum; Chromatography, Gel; Conotoxins; Fluorescent Dyes; Fura-2; Intercellular Signaling Peptides and Proteins; Mass Spectrometry; Mice; Molecular Sequence Data; Mollusk Venoms; N-Methylaspartate; Neurons; Peptides; Rats; Seizures; Sequence Homology, Nucleic Acid; Snails