PMID: 11331410May 2, 2001Paper

Amino acid determinants for NMDA receptor inhibition by conantokin-T

Journal of Neurochemistry
S E WarderM Prorok

Abstract

Several derivatives of conantokin-T (con-T), a naturally occurring, gamma-carboxyglutamate (Gla)-containing peptide with NMDA receptor (NMDAR) antagonist properties, were synthesized and evaluated for their ability to displace [(3)H]MK-801 from adult rat forebrain membranes. Analyses of progressive C-terminal truncation analogs of the parent 21-mer revealed gradual losses in activity with decreased chain length. In this series, con-T[1-8] was identified as the shortest variant capable of manifesting inhibitory activity (< 1% of the parent peptide). Ala substitution studies of individual residues identified Gly1, Gla3, Met8 and Leu12 as important for activity, while Glu2, Gla4 and Tyr5 were shown to be essential in this regard. The effect of side-chain length and charge in the N-terminal region was probed by single amino acid replacements. No correlation was observed between potencies and circular dichroism-derived helical contents of the con-T derivatives. Further elaboration of structure-function relationships in con-T was effected through the design and synthesis of helically constrained and destabilized analogs. The results of the current study were compared with those of a previous investigation on con-G, a related conantok...Continue Reading

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Citations

Nov 11, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sara E CnuddeJames H Geiger
Feb 11, 2014·Toxicon : Official Journal of the International Society on Toxinology·Randall J PlattBaldomero M Olivera
May 20, 2003·The Journal of Peptide Research : Official Journal of the American Peptide Society·R C KleinF J Castellino
Jun 24, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Konkallu H GowdBaldomero M Olivera

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