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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Bogacheva, Mariia^1,2  Egorova, Anna¹  Slita, Anna¹  Maretina, Marianna¹  Baranov, Vladislav¹  Kiselev, Anton¹ 

[1] DO Ott Res Inst Obstet Gynecol & Reproductol, Mendeleevskaya Line,3, St Petersburg 199034, Russia

[2] Univ Helsinki, Ctr Drug Res, Fac Pharm, POB 56, FI-00014 Helsinki, Finland

关键词: SV40;    Nuclear localization signal;    Cross-linking peptides;    DNA;    Transfection;    Intranuclear delivery;    Non-viral vectors;   

DOI  :  10.1016/j.bmcl.2017.10.001

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free