title: From venoms to BBB shuttles: Synthesis and blood-brain barrier transport assessment of apamin and a nontoxic analog.
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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona Science Park, Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Benjamí
authors.initials: B
authors.lastname: Oller-Salvia
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixidó
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D001030:Apamin; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain; D010455:Peptides; D014688:Venoms
chemical_list: D010455:Peptides; D014688:Venoms; D001030:Apamin
keywords: apamin; blood-brain barrier; blood-brain barrier shuttles; brain delivery; peptide shuttles; venoms