Design and characterization of novel cell-penetrating peptides from pituitary adenylate cyclase-activating polypeptide

Autor: Hubert Vaudry, David Vaudry, Ngoc-Duc Doan, Myriam Létourneau, Nicolas Doucet, David Chatenet, Benjamin Folch, Alain Fournier
Přispěvatelé: Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), This work was supported by the CIHR grant #102734 (Alain Fournier) and NSERC Discovery grant GPIN 402623-2011 (Nicolas Doucet). Nicolas Doucet also acknowledges supports from the FRQNT Strategic Cluster 'Regroupement Québécois de Recherche sur la Fonction, la Structure et l'Ingénierie des Protéines' (PROTEO) and the FRQS Strategic Cluster 'Groupe de Recherche Axé sur la Structure des Protéines' (GRASP).
Rok vydání: 2012
Předmět:
media_common.quotation_subject
Green Fluorescent Proteins
Endogenous cell-penetrating peptide
Pharmaceutical Science
MESH: Cricetinae
CHO Cells
Cell-Penetrating Peptides
MESH: Drug Design
Endocytosis
PACAP
Transfection
03 medical and health sciences
0302 clinical medicine
MESH: Green Fluorescent Proteins
Cricetulus
MESH: Cricetulus
MESH: CHO Cells
MESH: Plasmids
Cellular uptake
Cricetinae
Animals
Humans
MESH: Animals
Internalization
030304 developmental biology
media_common
MESH: Cell-Penetrating Peptides
0303 health sciences
MESH: Humans
Chemistry
Pinocytosis
MESH: Transfection
HEK 293 cells
MESH: Pituitary Adenylate Cyclase-Activating Polypeptide
In vitro
HEK293 Cells
Biochemistry
Lipofectamine
MESH: HEK293 Cells
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Drug Design
Drug delivery
Pituitary Adenylate Cyclase-Activating Polypeptide
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Intracellular
Plasmids
Zdroj: Journal of Controlled Release
Journal of Controlled Release, Elsevier, 2012, 163 (2), pp.256-65. ⟨10.1016/j.jconrel.2012.08.021⟩
ISSN: 1873-4995
0168-3659
DOI: 10.1016/j.jconrel.2012.08.021⟩
Popis: International audience; The discovery of cell-penetrating peptide opened up new promising avenues for the non-invasive delivery of non-permeable biomolecules within the intracellular compartment. However, some setbacks such as possible toxic effects or unexpected immunological responses have limited their use in clinic. To overcome these obstacles, we investigated the use of novel cell-penetrating peptides (CPPs) derived from the endogenous neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP). First, we demonstrated the propensity of native PACAP isoforms (PACAP27 and PACAP38) to efficiently deliver a large and non-permeable molecule, i.e. streptavidin, into cells. An inactive modified fragment of PACAP38, i.e. [Arg(17)]PACAP(11-38), with preserved cell-penetrating physico-chemical properties, was also synthesized and successfully use for the intracellular delivery of various cargoes such as small molecules, peptides, proteins, and polynucleotides. Especially, its effectiveness as a transfection agent was comparable to Lipofectamine 2000 while being non-toxic for cells. Uptake mechanism studies demonstrated that direct translocation, caveolae-dependent endocytosis and macropinocytosis were involved in the internalization of [Arg(17)]PACAP(11-38). This study not only opened up a new aspect in the usefulness of PACAP and its derivatives for therapeutic application but also contributed to the identification of new members of the CPP family. As such, inactive PACAP-related analogs could represent excellent vectors for in vitro and in vivo applications.
Databáze: OpenAIRE
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