Multiblock Reducible Copolypeptides Containing Histidine-Rich and Nuclear Localization Sequences for Gene Delivery
Identifieur interne : 001C19 ( Main/Exploration ); précédent : 001C18; suivant : 001C20Multiblock Reducible Copolypeptides Containing Histidine-Rich and Nuclear Localization Sequences for Gene Delivery
Auteurs : Devika Soundara Manickam [États-Unis] ; David Oupick [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 2006.
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.
Url:
DOI: 10.1021/bc060104k
Affiliations:
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Localization Sequences for Gene Delivery</title><author><name sortKey="Manickam, Devika Soundara" sort="Manickam, Devika Soundara" uniqKey="Manickam D" first="Devika Soundara" last="Manickam">Devika Soundara Manickam</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Department of Pharmaceutical Sciences, Wayne State University, Detroit</wicri:cityArea></affiliation></author><author><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Department of Pharmaceutical Sciences, Wayne State University, Detroit</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Bioconjugate Chemistry</title><title level="j" type="abbrev">Bioconjugate Chem.</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2006-10-20">2006</date><date when="2006-11-15">2006</date><biblScope unit="vol">17</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1395">1395</biblScope><biblScope unit="page" to="1403">1403</biblScope></imprint><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1043-1802</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Michigan</li></region></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Manickam, Devika Soundara" sort="Manickam, Devika Soundara" uniqKey="Manickam D" first="Devika Soundara" last="Manickam">Devika Soundara Manickam</name></region><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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