Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes.
cell penetrating peptide
intracellular delivery
multimerization
oligosaccharides
peptide nucleic acids
peptides
Journal
Journal of peptide science : an official publication of the European Peptide Society
ISSN: 1099-1387
Titre abrégé: J Pept Sci
Pays: England
ID NLM: 9506309
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
14
10
2020
revised:
21
12
2020
accepted:
21
12
2020
pubmed:
19
1
2021
medline:
6
10
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell-penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell-impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell-targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low-toxic cationic amphiphilic peptide L17E derived from M-lycotoxin. Here, we show that cell-penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran-L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light-triggered activation of cellular uptake.
Substances chimiques
Cell-Penetrating Peptides
0
Dextrans
0
Fluorescent Dyes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3298Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SPP1623
Informations de copyright
© 2021 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
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