期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 135, 期 25, 页码 9295-9298出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja404153m
关键词
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资金
- University of Geneva
- NMR Platform
- MS Platform
- Biomolecular Screening Facility (EPFL)
- European Research Council (ERC Advanced Investigator)
- NCCR Chemical Biology
- Swiss NSF
- JSPS Research Fellowship
Dynamic amphiphiles are amphiphiles with dynamic covalent bridges between their hydrophilic heads and their hydrophobic tails. Their usefulness to activate ion transporters, for odorant release, and for differential sensing of odorants and perfumes, has been demonstrated recently. Here, we report that the same fragrant dynamic amphiphiles are ideal to screen for new siRNA transfection agents. The advantages of this approach include rapid access to fairly large libraries of complex structures, and possible transformation en route to assist uptake and minimize toxicity. We report single-component systems that exceed the best commercially available multicomponent cocktails with regard to both efficiency and velocity of EGFP knockdown in HeLa cells. In human primary fibroblasts, siRNA-mediated enzyme knockdown nearly doubled from >30% for Lipofectamine to >60% for our best hit. The identified structures were predictable neither from literature nor from results in fluorogenic vesicles and thus support the importance of conceptually innovative screening approaches.
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