Combinatorial Synthesis and High-Throughput Screening of Alkyl Amines for Nonviral Gene Delivery
作者:Linxian Li、Fengjian Wang、Yihang Wu、Gary Davidson、Pavel A. Levkin
DOI:10.1021/bc400158w
日期:2013.9.18
method based on an alkylation of amines, allowing for the fast parallel synthesis of libraries of cationic lipid-like molecules (lipidoids). We exploited the method to synthesize 200 lipidoids, which were screened for their transfection efficiency in HEK293T cells. The screen resulted in about 2% of new lipidoids capable of efficient cell transfection similar or higher than the efficiency of Lipofectamine
质粒DNA和siRNA高效传递到细胞中对于生物学和生物医学研究至关重要。尽管为开发有效的非病毒载体,例如阳离子脂质和聚合物,已经做出了巨大的努力,但是大多数载体需要多步合成,这使得这种载体的快速结构优化和组合合成变得复杂。在这里,我们提出了一种基于胺烷基化的简便,单步方法,可以快速并行合成阳离子脂质样分子(类脂质)的文库。我们利用该方法合成了200个类脂质,筛选了它们在HEK293T细胞中的转染效率。筛选后,大约有2%的新型脂质能够有效转染细胞,其效率与Lipofectamine 2000相似或更高。此外,