Acc Chem Res. 2015 May 19;48(5):1319-31. doi: 10.1021/acs.accounts.5b00109.
The programmability of oligonucleotide hybridization offers an attractive platform for the design of assemblies with emergent properties or functions. Developments in DNA nanotechnologies have transformed our thinking about the applications of nucleic acids. Progress from designed assemblies to functional outputs will continue to benefit from functionalities added to the nucleic acids that can participate in reactions or interactions beyond hybridization. In that respect, peptide nucleic acids (PNAs) are interesting because they combine the hybridization properties of DNA with the modularity of peptides. In fact, PNAs form more stable duplexes with DNA or RNA than the corresponding natural homoduplexes. The high stability achieved with shorter oligomers (an 8-mer is sufficient for a stable duplex at room temperature) typically results in very high sequence fidelity in the hybridization with negligible impact of the ionic strength of the buffer due to the lack of electrostatic repulsion between the duplex strands. The simple peptidic backbone of PNA has been shown to be tolerant of modifications with substitutions that further enhance the duplex stability while providing opportunities for functionalization. Moreover, the metabolic stability of PNAs facilitates their integration into systems that interface with biology. Over the past decade, there has been a growing interest in using PNAs as biosupramolecular tags to program assemblies and reactions. A series of robust templated reactions have been developed with functionalized PNA. These reactions can be used to translate DNA templates into functional polymers of unprecedented complexity, fluorescent outputs, or bioactive small molecules. Furthermore, cellular nucleic acids (mRNA or miRNA) have been harnessed to promote assemblies and reactions in live cells. The tolerance of PNA synthesis also lends itself to the encoding of small molecules that can be further assembled on the basis of their nucleic acid sequences. It is now well-established that hybridization-based assemblies displaying two or more ligands can interact synergistically with a target biomolecule. These assemblies have now been shown to be functional in vivo. Similarly, PNA-tagged macromolecules have been used to prepare bioactive assemblies and three-dimensional nanostructures. Several technologies based on DNA-templated synthesis of sequence-defined polymers or DNA-templated display of ligands have been shown to be compatible with reiterative cycles of selection/amplification starting with large libraries of DNA templates, bringing the power of in vitro evolution to synthetic molecules and offering the possibility of exploring uncharted molecular diversity space with unprecedented scope and speed.
寡核苷酸杂交的可编程性为具有新兴特性或功能的组装体设计提供了一个有吸引力的平台。DNA 纳米技术的发展改变了我们对核酸应用的思考。从设计的组装体到功能输出的进展将继续受益于添加到核酸中的功能，这些功能可以参与杂交以外的反应或相互作用。在这方面，肽核酸 (PNA) 很有趣，因为它们结合了 DNA 的杂交特性和肽的模块性。事实上，PNA 与 DNA 或 RNA 形成比相应的天然同源双链更稳定的双链体。通过使用较短的寡聚物（在室温下，8 个碱基足以形成稳定的双链体）实现的高稳定性通常导致在杂交中具有非常高的序列保真度，由于双链体之间缺乏静电排斥，缓冲液的离子强度几乎没有影响。PNA 的简单肽骨架被证明能够耐受修饰，这些修饰进一步增强了双链体的稳定性，同时为功能化提供了机会。此外，PNA 的代谢稳定性促进了它们与生物学接口系统的整合。在过去的十年中，人们对使用 PNA 作为生物超分子标签来编程组装体和反应产生了越来越大的兴趣。已经开发出一系列带有功能化 PNA 的稳健模板反应。这些反应可用于将 DNA 模板转化为具有前所未有的复杂性、荧光输出或生物活性小分子的功能聚合物。此外，细胞内核酸（mRNA 或 miRNA）已被用于促进活细胞中的组装体和反应。PNA 合成的耐受性也适合于进一步基于其核酸序列组装的小分子的编码。现在已经确立，显示两种或更多配体的基于杂交的组装体可以与靶生物分子协同相互作用。这些组装体现已被证明在体内具有功能。同样，PNA 标记的大分子已被用于制备生物活性组装体和三维纳米结构。已经证明，几种基于 DNA 模板合成序列定义聚合物或 DNA 模板显示配体的技术与从大型 DNA 模板文库开始的重复选择/扩增循环兼容，为合成分子带来了体外进化的力量，并提供了以空前的范围和速度探索未知分子多样性空间的可能性。
