From venoms to BBB shuttles: Synthesis and blood–brain barrier transport assessment of apamin and a nontoxic analog

Authors

  • Benjamí Oller-Salvia,

    1. Institute for Research in Biomedicine (IRB Barcelona) Barcelona Science Park, Baldiri Reixac 10, Barcelona, Spain
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  • Meritxell Teixidó,

    1. Institute for Research in Biomedicine (IRB Barcelona) Barcelona Science Park, Baldiri Reixac 10, Barcelona, Spain
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  • Ernest Giralt

    1. Institute for Research in Biomedicine (IRB Barcelona) Barcelona Science Park, Baldiri Reixac 10, Barcelona, Spain
    2. Department of Organic Chemistry, University of Barcelona, Martí i Franquès 1-11, Barcelona, Spain
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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Correspondence to: Meritxell Teixidó, Institute for Research in Biomedicine, (IRBBarcelona), Baldiri Reixac 10, Barcelona 08028, Spain; e-mail: meritxell.teixido@irbbarcelona.org (or)

Ernest Giralt, Institute for Research in Biomedicine, (IRB Barcelona), Baldiri Reixac 10, Barcelona 08028, Spain; e-mail: ernest.giralt@irbbarcelona.org

ABSTRACT

Venoms are currently the focus of many drug discovery programs because they contain highly bioactive and selective components. Among them, apamin, a peptide found in bee venom, has received considerable attention because of its affinity for certain potassium channels and also because of its interesting structure and high stability to extreme pH and temperatures. Although apamin has long been claimed to cross the blood–brain barrier (BBB), only a few studies have been performed producing controversial results. In this article, it is shown that not only apamin is indeed able to penetrate the BBB in a cell-based model but also that an analog reported to be nontoxic passes through this barrier. Furthermore, the permeability values obtained, together with some evidence of an active transport mechanism and an amazing stability to serum proteases, make these peptides promising candidates for BBB shuttles. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 675–686, 2013.

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