Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 135, Issue 25, Pages 9295-9298Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja404153m
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Funding
- 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
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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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