A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery

被引：194

作者：

Murphy, JE ^{[1
]}

Uno, T ^{[1
]}

Hamer, JD ^{[1
]}

Cohen, FE ^{[1
]}

Dwarki, V ^{[1
]}

Zuckermann, RN ^{[1
]}

机构：

[1] Chiron Corp, Chiron Technol, Emeryville, CA 94608 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1998年 / 95卷 / 04期

关键词：

D O I：

10.1073/pnas.95.4.1517

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A family of N-substituted glycine oligomers (peptoids) of defined length and sequence are shown to condense plasmid DNA into small particles, protect it from nuclease degradation, and efficiently mediate the transfection of several cell lines. The oligomers were discovered by screening a combinatorial library of cationic peptoids that varied in length, density of charge, side-chain shape, and hydrophobicity. Transfection activity and peptoid-DNA complex formation are shown to be highly dependent on the peptoid structure. The most active peptoid is a 36-mer that contains 12 cationic aminoethyl side chains, This molecule can be synthesized efficiently from readily available building blocks. The peptoid condenses plasmid DNA into uniform particles 50-100 nm in diameter and mediates the transfection of a number of cell lines with efficiencies greater than or comparable to DMRIE-C. Lipofectin, and Lipofectamine. Unlike many cationic lipids, peptoids are capable of working in the presence of serum.

引用

页码：1517 / 1522

页数：6

共 24 条

[1] Chiral N-substituted glycines can form stable helical conformations [J].