Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Biomacromolecules. 2011 Aug 8;12(8):3078-83. doi: 10.1021/bm200694u. Epub 2011 Jun 30.
Protein transduction domains (PTDs) that readily transverse cellular membranes are of great interest and are attractive tools for the intracellular delivery of bioactive molecules. Learning to program synthetic polymers and oligomers with the appropriate chemical information to capture adequately the biological activity of proteins is critical to our improved understanding of how these natural molecules work. In addition, the versatility of these synthetic mimics provides the opportunity to discover analogs with superior properties compared with their native sequences. Here we report the first detailed structure-activity relationship of a new PTD family of polymers based on a completely abiotic backbone. The synthetic approach easily allows doubling the density of guanidine functional groups, which increases the transduction efficiency of the sequences. Cellular uptake studies on three different cell lines (HEK 293T, CHO, and Jurkat T cells) confirm that these synthetic analogs are highly efficient novel protein transduction domain mimics (PTDMs), which are more effective than TAT(49-57) and nonaarginine (R9) and also highlight the usefulness of polymer chemistry at the chemistry-biology interface.
蛋白转导结构域（PTDs）能够轻易穿过细胞膜，因此备受关注，是将生物活性分子递送至细胞内的有效工具。要想深入理解这些天然分子的作用机制，我们必须学会用适当的化学信息来设计合成聚合物和寡聚物，以充分模拟蛋白质的生物活性。此外，这些合成模拟物的多功能性为发现具有比天然序列更优越性能的类似物提供了机会。在这里，我们报道了基于完全非生物骨架的新型 PTD 聚合物家族的首个详细的结构-活性关系。这种合成方法可以轻松地将胍基官能团的密度增加一倍，从而提高序列的转导效率。对三种不同细胞系（HEK 293T、CHO 和 Jurkat T 细胞）的细胞摄取研究证实，这些合成类似物是高效的新型蛋白转导结构域模拟物（PTDMs），比 TAT（49-57）和九聚精氨酸（R9）更有效，同时也突出了聚合物化学在化学-生物学界面的有用性。
