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Santiago de Querétaro, Mexico

Aguilar M.B.,Laboratorio Of Neurofarmacologia Marina | Zugasti-Cruz A.,Laboratorio Of Neurofarmacologia Marina | Falcon A.,Laboratorio Of Neurofarmacologia Marina | Batista C.V.F.,National Autonomous University of Mexico | And 2 more authors.
Peptides | Year: 2013

The present study details the purification, the amino acid sequence determination, and a preliminary characterization of the biological effects in mice of a new conotoxin from the venom of Conus cancellatus (jr. syn.: Conus austini), a worm-hunting cone snail collected in the western Gulf of Mexico (Mexico). The 23-Amino acid peptide, called as25a, is characterized by the sequence pattern CX1CX2CX8CX 1CCX5, which is, for conotoxins, a new arrangement of six cysteines (framework XXV) that form three disulfide bridges. The primary structure (CKCPSCNFNDVTENCKCCIFRQP*;*, amidated C-terminus; calculated monoisotopic mass, 2644.09 Da) was established by automated Edman degradation after reduction and alkylation, and MALDI-TOF and ESI mass spectrometry (monoisotopic mass, 2644.12/2644.08 Da). Upon intracranial injection in mice, the purified peptide provokes paralysis of the hind limbs and death with a dose of 240 pmol (∼0.635 μg, ∼24.9 ng/g). In addition, a post-translational variant of this peptide (as25b) was identified and determined to contain two hydroxyproline residues. These peptides may represent a novel conotoxin gene superfamily. © 2013 Elsevier Inc.

Aguilar M.B.,Laboratorio Of Neurofarmacologia Marina | Ortiz E.,National Autonomous University of Mexico | Kaas Q.,University of Queensland | Lopez-Vera E.,Laboratorio Of Neurofarmacologia Marina | And 4 more authors.
Peptides | Year: 2013

Peptide de13a was previously purified from the venom of the worm-hunting cone snail Conus delessertii from the Yucatán Channel, México. This peptide has eight cysteine (Cys) residues in the unique arrangement CCCCCCCC, which defines the cysteine framework XIII ("" represents one or more non-Cys residues). Remarkably, δ-hydroxy-lysine residues have been found only in conotoxin de13a, which also contains an unusually high proportion of hydroxylated amino acid residues. Here, we report the cDNA cloning of the complete precursor De13.1 of a related peptide, de13b, which has the same Cys framework and inter-Cys spacings as peptide de13a, and shares high protein/nucleic acid sequence identity (87%/90%) with de13a, suggesting that both peptides belong to the same conotoxin gene superfamily. Analysis of the signal peptide of precursor De13.1 reveals that this precursor belongs to a novel conotoxin gene superfamily that we chose to name gene superfamily G. Thus far superfamily G only includes two peptides, each of which contains the same, distinctive Cys framework and a high proportion of amino acid residues with hydroxylated side chains. © 2013 Elsevier Inc.

Morales-Gonzalez D.,Laboratorio Of Neurofarmacologia Marina | Morales-Gonzalez D.,National Autonomous University of Mexico | Flores-Martinez E.,Laboratorio Of Neurofarmacologia Marina | Flores-Martinez E.,National Autonomous University of Mexico | And 8 more authors.
Peptides | Year: 2015

Conus marine snails (∼500 species) are tropical predators that use venoms mainly to capture prey and defend themselves from predators. The principal components of these venoms are peptides that are known as "conotoxins" and generally comprise 7-40 amino acid residues, including 0-5 disulfide bridges and distinct posttranslational modifications. The most common molecular targets of conotoxins are voltage- and ligand-gated ion channels, G protein-coupled receptors, and neurotransmitter transporters, to which they bind, typically, with high affinity and specificity. Due to these properties, several conotoxins have become molecular probes, medicines, and leads for drug design. Conotoxins have been classified into genetic superfamilies based on the signal sequence of their precursors, and into pharmacological families according to their molecular targets. The objective of this work was to identify and analyze partial cDNAs encoding conotoxin precursors belonging to the A superfamily from Conus brunneus, Conus nux, and Conus princeps. These are vermivorous species of the Mexican Pacific coast from which only one A-conotoxin, and few O- and I2-conotoxins have been reported. Employing RT-PCR, we identified 30 distinct precursors that contain 13 different predicted mature toxins. With the exception of two groups of four highly similar peptides, these toxins are diverse at both the sequence and the physicochemical levels, and they belong to the 4/3, 4/4, 4/5, 4/6, and 4/7 structural subfamilies. These toxins are predicted to target diverse nicotinic acetylcholine receptor (nAChR) subtypes: nx1d, muscle; pi1a-pi1d, α3β2, α7, and/or α9α10; br1a, muscle, α3β4, and/or α4β2; and nx1a-nx1c/pi1g and pi1h, α3β2, α3β4, α9β10, and/or α7. © 2015 Elsevier Inc. All rights reserved.

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