Dépôt numérique

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

Doan, Ngoc-Duc; Létourneau, Myriam; Vaudry, David; Doucet, Nicolas ORCID logoORCID: https://orcid.org/0000-0002-1952-9380; Folch, Benjamin; Vaudry, Hubert; Fournier, Alain et Chatenet, David ORCID logoORCID: https://orcid.org/0000-0002-7270-4328 (2012). Design and characterization of novel cell-penetrating peptides from pituitary adenylate cyclase-activating polypeptide Journal of Controlled Release , vol. 163 , nº 2. pp. 256-265. DOI: 10.1016/j.jconrel.2012.08.021.

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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.

Type de document: Article
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 07 mars 2024 16:29
Dernière modification: 07 mars 2024 16:30
URI: https://espace.inrs.ca/id/eprint/14014

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