Multiblock reducible copolypeptides containing histidine-rich and nuclear localization sequences for gene delivery

Devika Soundara Manickam, David Oupický

Research output: Contribution to journalArticle

83 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1395-1403
Number of pages9
JournalBioconjugate Chemistry
Volume17
Issue number6
DOIs
StatePublished - Nov 1 2006

Fingerprint

Histidine
Peptides
Genes
Polyethyleneimine
Transfection
Polypeptides
Endothelial cells
Cell membranes
Cytotoxicity
Charge density
Intracellular Membranes
Rigidity
Copolymerization
Poisons
DNA
Disulfides
Molecular weight
Cells
Oxidation-Reduction
Membranes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Multiblock reducible copolypeptides containing histidine-rich and nuclear localization sequences for gene delivery. / Manickam, Devika Soundara; Oupický, David.

In: Bioconjugate Chemistry, Vol. 17, No. 6, 01.11.2006, p. 1395-1403.

Research output: Contribution to journalArticle

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