Philippine E-Journals

Conantokin-T A Γ-Carboxyglutamate Containing Peptide With N-Methyl-D-Aspartate Antagonist Activity

Julie A. Haack | Jean Riviers | Thomas N. Parks | E. Edward Mena | Cruz J. Lourdes | Baldomero M. Olivera

 

Abstract:

Conantokin-T, a 21-amino acid peptide which induces sleep-like symtoms in young mice was purified from the venom of the fish -hunting cone snail, Conus tulipa. The amino acid sequence of the pertide was determined e~d verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, 'Y-carboxyglutamate (Gla). The sequence of the pe~tide is: Gly-Glu-Gla-Gla-TyrGln- Lys-Met-Leu-Gla-Asn-Leu-Arg-Gla-Ala-Glu-Val-Lys-Lys-Asn-Ala-NH . Conantokin-T inhibits ~methyl- D aspartate (NMDA) receptor-medicated 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.