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      Antimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators

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          Abstract

          Animals using toxic peptides and proteins for predation or defense typically depend on specialized morphological structures, like fangs, spines, or a stinger, for effective intoxication. Here we show that amphibian poisons instead incorporate their own molecular system for toxin delivery to attacking predators. Skin-secreted peptides, generally considered part of the amphibian immune system, permeabilize oral epithelial tissue and enable fast access of cosecreted toxins to the predator’s bloodstream and organs. This absorption-enhancing system exists in at least three distantly related frog lineages and is likely to be a widespread adaptation, determining the outcome of predator–prey encounters in hundreds of species.

          Abstract

          To avoid being eaten, poisonous prey animals must rely on fast passage of toxins across a predator’s oral tissue, a major barrier to large molecules. Here, Raaymakers et al. show that antimicrobial peptides co secreted with frog toxins enhance intoxication of a snake predator by permeabilizing oral cell layers.

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          Most cited references51

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          Approaches for enhancing oral bioavailability of peptides and proteins.

          Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1-2%). An ideal oral drug delivery system should be capable of (a) maintaining the integrity of protein molecules until it reaches the site of absorption, (b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and (c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. Copyright © 2013 Elsevier B.V. All rights reserved.
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            Three Valuable Peptides from Bee and Wasp Venoms for Therapeutic and Biotechnological Use: Melittin, Apamin and Mastoparan

            While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine.
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              The chemistry and biological activities of peptides from amphibian skin secretions.

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                Author and article information

                Contributors
                Kim.Roelants@vub.be
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 November 2017
                14 November 2017
                2017
                : 8
                : 1495
                Affiliations
                [1 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Amphibian Evolution Lab, Biology Department, , Vrije Universiteit Brussel, ; Pleinlaan 2, 1050 Elsene, Belgium
                [2 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, , Ghent University, ; Salisburylaan 133, 9820 Merelbeke, Belgium
                [3 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Department of Nuclear Medicine, UZ Brussel and In vivo Cellular and Molecular Imaging, , Vrije Universiteit Brussel, ; Laarbeeklaan 103, 1090 Jette, Belgium
                [4 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Research Group of Organic Chemistry, Department of Chemistry and Department of Bio-engineering Sciences, , Vrije Universiteit Brussel, ; Pleinlaan 2, 1050 Elsene, Belgium
                [5 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Biology, Nematology Research Unit, Faculty of Science, , Ghent University, ; 9000 Ghent, Belgium
                Author information
                http://orcid.org/0000-0001-7609-5649
                Article
                1710
                10.1038/s41467-017-01710-1
                5686178
                29138448
                19711b8e-e87a-4a2d-899c-0618ce52e215
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 April 2017
                : 10 October 2017
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