State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, College of Chemical Engineering , China University of Petroleum (East China) , 66 Changjiang West Road , Qingdao 266580 , China.
Key Laboratory of Colloid and Interface Science, Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry , Chinese Academy of Sciences , Beijing 100190 , China.
ACS Appl Mater Interfaces. 2018 Jul 25;10(29):24349-24360. doi: 10.1021/acsami.8b00246. Epub 2018 Jul 16.
A series of surfactant-like peptides have been designed for inducing DNA condensation, which are all comprised of the same set of amino acids in different sequences. Results from experiments and molecular dynamics simulations show that the peptide's self-assembly and DNA-interaction behaviors can be well manipulated through sequence variation. With optimized pairing modes between the β-sheets, the peptide of IVAGK can induce efficient DNA condensation into virus-mimicking structures. The condensation involves two steps; the peptide molecules first bind onto the DNA chain through electrostatic interactions and then self-associate into β-sheets under hydrophobic interactions and hydrogen bonding. In such condensates, the peptide β-sheets act as scaffolds to assist the ordered arrangement of DNA, mimicking the very nature of the virus capsid in helping DNA packaging. Such a hierarchy affords an extremely stable structure to attain the highly condensed state and protect DNA against enzymatic degradation. Moreover, the condensate size can be well tuned by the DNA length. The condensates with smaller sizes and narrow size distribution can deliver DNA efficiently into cells. The study helps not only for probing into the DNA packaging mechanism in virus but also delineating the role of peptide self-assembly in DNA condensation, which may lead to development of peptide-based gene vectors for therapeutic applications.
已经设计了一系列具有表面活性剂特性的肽用于诱导 DNA 凝聚，它们都由不同序列的相同氨基酸组成。实验和分子动力学模拟的结果表明，可以通过序列变化很好地控制肽的自组装和 DNA 相互作用行为。通过优化 β-折叠之间的配对模式，IVAGK 肽可以诱导 DNA 有效地凝聚成类似病毒的结构。这种凝聚涉及两个步骤；肽分子首先通过静电相互作用结合到 DNA 链上，然后在疏水相互作用和氢键的作用下自组装成 β-折叠。在这种凝聚物中，肽的β-折叠作为支架来帮助 DNA 的有序排列，模拟病毒衣壳帮助 DNA 包装的本质。这种层次结构提供了极其稳定的结构，以达到高度凝聚的状态，并保护 DNA 免受酶降解。此外，通过 DNA 长度可以很好地调节凝聚物的大小。较小尺寸和较窄尺寸分布的凝聚物可以有效地将 DNA 递送到细胞中。这项研究不仅有助于探究病毒中的 DNA 包装机制，还阐明了肽自组装在 DNA 凝聚中的作用，这可能为治疗应用的基于肽的基因载体的发展提供了思路。
