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Quaternized poly(4-vinylpyridine)s as model gene delivery polycations: Structure-function study by modification of side chain hydrophobicity and degree of alkylationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: San Juan Aurelie, Letourneur Didier, Izumrudov Vladimir A.
- Журнал: Bioconjugate Chemistry
- Том: 18
- Номер: 3
- Год издания: 2007
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 922
- Последняя страница: 928
- DOI: 10.1021/bc060317+
- Аннотация: To optimize polycation-based gene delivery agents, the influence of molecular characteristics of the polycations on physicochemical properties of polycation/DNA complexes and their relationships to cellular gene transfer need to be understood. With this aim, we have synthesized a series of model polymers based on quaternized poly(4-vinylpyridine)s (CnPVP-beta) with the same DP of 1600 but differing by the number n of methylene groups in N-alkyl ester substituents from 1 to 6 and/or by degree of alkylation beta from 25% to 95%. For polycations CnPVP-95, the efficiency of transfection of a plasmid vector expressing a secreted form of alkaline phosphatase started to be detectable at n = 4, noticeable at n = 5, and again undetectable at n = 6. A decrease in beta of active C5PVP-95 from 95% to 65% resulted in a further noticeable increase of activity with a 9-fold increase for C5PVP-65. This finding was attributed to the proton sponge mechanism due to protonation of non-alkylated pyridine moieties of CnPVP-beta/DNA complexes in slightly acidic media that was supported by the fluorescence quenching assay. The data demonstrate the advantages of partial alkylation of tertiary polyamines with medium-length alkyl agents for preparation of efficient nonviral gene delivery vectors.
- Добавил в систему: izumrudov