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A multidisciplinary strategy for discovery of new Conus venom peptides combines molecular genetics and phylogenetics with peptide chemistry and neuropharmacology. Here we describe application of this approach to the conantokin family of conopeptides targeting NMDA receptors. A new conantokin from Conus rolani, ConRl‐A, was identified using molecular phylogeny and subsequently synthesized and functionally...
The conantokins are a family of Conus venom peptides (17–27AA) that are N-methyl-d-aspartate (NMDA) receptor antagonists. Conantokins lack disulfide bridges (six out of seven previously characterized peptides are linear), but contain multiple residues of γ-carboxyglutamate. These post-translationally modified amino acids confer the largely helical structure of conantokins by coordinating divalent...
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