Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery

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http://hdl.handle.net/10138/308069

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Bogacheva , M , Egorova , A , Slita , A , Maretina , M , Baranov , V & Kiselev , A 2017 , ' Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery ' , Bioorganic & Medicinal Chemistry Letters , vol. 27 , no. 21 , pp. 4781-4785 . https://doi.org/10.1016/j.bmcl.2017.10.001

Title: Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery
Author: Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton
Contributor: University of Helsinki, Faculty of Pharmacy
Date: 2017-11-01
Language: eng
Number of pages: 5
Belongs to series: Bioorganic & Medicinal Chemistry Letters
ISSN: 0960-894X
URI: http://hdl.handle.net/10138/308069
Abstract: The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. (C) 2017 Elsevier Ltd. All rights reserved.
Subject: SV40
Nuclear localization signal
Cross-linking peptides
DNA
Transfection
Intranuclear delivery
Non-viral vectors
GENE DELIVERY
PLASMID DNA
TRANSFECTION EFFICIENCY
SYSTEMS
CELLS
MICROINJECTION
COMPLEXES
HISTIDINE
CARRIERS
BINDING
317 Pharmacy
116 Chemical sciences
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