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

• Published in: Biopolymers Vol. 100; no. 6; pp. 675 - 686
• Main Authors: Oller-Salvia, Benjamí, Teixidó, Meritxell, Giralt, Ernest
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2013
• Subjects: Apamin; Biological Transport; Blood-Brain Barrier; blood-brain barrier shuttles; Brain; brain delivery; peptide shuttles; Peptides; Venoms; blood-brain barrier; brain delivery; venoms; peptide shuttles; blood-brain barrier shuttles; apamin
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.22257

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.