Isolation of a Neuroactive Peptide from Conus mustelinus

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Cone Snails The cone snails (family Conoidea) are venomous marine gastropods usually found in tropical marine waters. There are more than 500 species of cone snails and they use their venom to capture prey and to defend themselves against predators. The cone snails are grouped according to their prey preference: worms, usually polychaetes; fish; and other gastropod mollusks (Olivera, 2002). The venom is composed of biologically active peptides, which are produced in the venom duct of the snail venom apparatus (Figure 1, Olivera 2002) and are pumped by the venom bulb through the proboscis. Figure 1. Conus venom apparatus: the venom bulb, venom duct, and the radular sac with the harpoons (radular teeth). (Olivera 2002) Conus Venom and Conotoxins Conus venoms contain biologically active components, called conotoxins (conopeptides) that target different molecular receptors. They are generally 10 to 35 amino acids long. They are stabilized by disulfide-linkages, usually through cysteine residues. Post-translational modifications to the amino acids are common, such as C-terminal amidation, 4-hydroxyproline and gamma-carboxylic glutamic acid. The mature peptide toxins in the venom are processed in the endoplasmic reticulum (ER) and in the Golgi apparatus. Conopeptides are expressed as precursor proteins and are organized as such in Figure 2. The ER signal is highly conserved and is used to define the gene superfamilies of the conopeptides (Kaas et al. 2010, 2012). Figure 2. An example of a conopeptide protein precursor, Ms20.1 precursor, indicating its signal sequence (pre region), its pro region, and the mature peptide region. Based on the characteristics of the conopeptides and their biological activity, they are classified... ... middle of paper ... ...Lluisma, A. (2012). Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes. Annals of the New York Academy of Sciences, 1267(1), 61-70. Olivera, B., Imperial, J., & Concepcion, G. (2013). Snail Peptides. Handbook of biologically active peptides (2nd ed., pp. 437-450). San Diego: Elsevier. Peracchia, C. (1994). Handbook of membrane channels: Molecular and cellular physiology. San Diego, CA: Academic Press. Schmidtko, A., Lötsch, J., Freynhagen, R., & Geisslinger, G. (2010). Ziconotide for treatment of severe chronic pain. The Lancet, 375(9725), 1569-1577. Via, M.C. (2008). [Executive Summary of the book Neurodegenerative Diseases: Next-Generation Drugs for Four Major Disorders]. Insight Pharma Reports.

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