conotoxin-gv and arcaine

Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex.

Topics: Amino Acid Sequence; Animals; Biguanides; Circular Dichroism; Conotoxins; Magnesium; Male; Molecular Sequence Data; N-Methylaspartate; Peptides, Cyclic; Polyamines; Rats; Rats, Sprague-Dawley; Spermine