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 organization: | Faculty of Pharmacy Tissue engineering for drug research |
Date: | 2017-11-01 |
Language: | eng |
Number of pages: | 5 |
Belongs to series: | Bioorganic & Medicinal Chemistry Letters |
ISSN: | 0960-894X |
DOI: | https://doi.org/10.1016/j.bmcl.2017.10.001 |
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 |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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