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Open AccessFeature PaperCommunication
Molecules 2017, 22(10), 1753;

A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Accepted: 14 October 2017 / Published: 18 October 2017
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
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The capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many drugs. Hence, finding safe shuttles able to overcome the BBB is of utmost importance. Herein, we identify a new BBB-translocating peptide with unique properties. For years it was thought that cationic sequences were mandatory for a cell-penetrating peptide (CPP) to achieve cellular internalization. Despite being anionic at physiological pH, PepNeg (sequence (SGTQEEY) is an efficient BBB translocator that is able to carry a large cargo (27 kDa), while maintaining BBB integrity. In addition, PepNeg is able to use two distinct methods of translocation, energy-dependent and -independent, suggesting that direct penetration might occur when low concentrations of peptide are presented to cells. The discovery of this new anionic trans-BBB peptide allows the development of new delivery systems to the CNS and contributes to the need to rethink the role of electrostatic attraction in BBB-translocation. View Full-Text
Keywords: cell-penetrating peptide; blood–brain barrier; anionic peptide; drug-delivery systems cell-penetrating peptide; blood–brain barrier; anionic peptide; drug-delivery systems

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Neves-Coelho, S.; Eleutério, R.P.; Enguita, F.J.; Neves, V.; Castanho, M.A.R.B. A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model. Molecules 2017, 22, 1753.

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