A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model
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 o...
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doaj-c905a82116424934ad6a5f882f92eb242020-11-24T23:23:53ZengMDPI AGMolecules1420-30492017-10-012210175310.3390/molecules22101753molecules22101753A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier ModelSara Neves-Coelho0Rute P. Eleutério1Francisco J. Enguita2Vera Neves3Miguel A. R. B. Castanho4Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, PortugalThe 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.https://www.mdpi.com/1420-3049/22/10/1753cell-penetrating peptideblood–brain barrieranionic peptidedrug-delivery systems |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sara Neves-Coelho Rute P. Eleutério Francisco J. Enguita Vera Neves Miguel A. R. B. Castanho |
spellingShingle |
Sara Neves-Coelho Rute P. Eleutério Francisco J. Enguita Vera Neves Miguel A. R. B. Castanho A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model Molecules cell-penetrating peptide blood–brain barrier anionic peptide drug-delivery systems |
author_facet |
Sara Neves-Coelho Rute P. Eleutério Francisco J. Enguita Vera Neves Miguel A. R. B. Castanho |
author_sort |
Sara Neves-Coelho |
title |
A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model |
title_short |
A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model |
title_full |
A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model |
title_fullStr |
A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model |
title_full_unstemmed |
A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model |
title_sort |
new noncanonical anionic peptide that translocates a cellular blood–brain barrier model |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-10-01 |
description |
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. |
topic |
cell-penetrating peptide blood–brain barrier anionic peptide drug-delivery systems |
url |
https://www.mdpi.com/1420-3049/22/10/1753 |
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