Novel Conantokins from Conus parius Venom Are Specific Antagonists of N-Methyl-D-aspartate Receptors (original) (raw)

Conantokin-T: A γ-carboxyglutamate containing peptide with N-methyl-D-aspartate antagonist activity

Journal of Biological Chemistry

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.

Peptide toxins from Conus geographus venom

Journal of Biological Chemistry, 1981

Three homologous toxic peptides which cause postsynaptic inhibition at the vertebrate neuromuscar junction have been purified from the venom of the marine snail Conus geographus.