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Updated: Jul 18, 2026

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
Published on: August 6, 2019
Multiblock reducible copolypeptides containing histidine-rich and nuclear localization sequences for gene delivery
Devika Soundara Manickam1, David Oupický
1Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Abstract:
Polyplexes sensitive to redox potential gradients represent promising gene delivery vectors. High molecular weight polypeptides containing disulfide bonds in the backbone were synthesized by an oxidative copolymerization of a histidine-rich peptide (HRP) and a nuclear localization sequence (NLS) peptide. The synthetic approach allowed an easy synthesis of reducible copolypeptides (rCPP) with different relative contents of the HRP and NLS sequences. Cytotoxicity and transfection activity of rCPP-based DNA polyplexes were evaluated in vitro. In comparison with control polyethylenimine (PEI), only minimum toxic effects of rCPPs were observed on the metabolic activity and membrane integrity of human endothelial cells. These findings are predominantly ascribed to favorable structural features like lower charge density and higher chain rigidity of the rCPPs compared to PEI and also to a reductive intracellular and plasma membrane degradation. Transfection activity in all tested cell lines increased with increasing content of the HRP sequence in the rCPPs, while no clearly measurable effect of the NLS sequence was found.
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