Bilingual Peptide Nucleic Acids: Encoding the Languages of Nucleic Acids and Proteins in a Single Self-Assembling Biopolymer
Bilingual Peptide Nucleic Acids: Encoding the Languages of Nucleic Acids and Proteins in a Single Self-Assembling Biopolymer
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DOI：
10.1021/jacs.9b09146
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发表时间：
2019-12-04
影响因子：
15
通讯作者：
Heemstra, Jennifer M.
中科院分区：
文献类型：
--
作者：
Swenson, Colin S.;Velusamy, Arventh;Heemstra, Jennifer M.
核酸和蛋白质是支持地球上所有生命的基本生物聚合物。核酸在碱基序列中存储着大量的信息，而多肽和蛋白质则利用不同的氨基酸功能基团来采用复杂的结构和执行广泛的活动。尽管自然界已经进化出了读取核酸密码并将其翻译成氨基酸密码的机器，但现有的生物聚合物仅限于单独编码氨基酸或核苷酸序列，限制了它们在医学和生物技术中的潜在应用。在这里，我们描述了一种双语生物聚合物的设计、合成和刺激响应组装行为，它将氨基酸和碱基序列整合到一个单肽核酸(PNA)支架中，使三级结构行为和可编程分子识别能力能够进行可调存储和检索。沿着PNA主链掺入一段确定的氨基酸侧链序列可产生具有“蛋白质编码”的两亲分子，该编码可引导在水条件下自组装成胶束结构。然而，这些两亲性分子也带有“核苷酸密码”，因此随后引入互补的RNA链会通过杂交诱导序列特异性的组装中断。总之，这些特性将双语PNA确立为一种强大的生物聚合物，它结合了两个信息系统，以利用结构响应性和序列识别。PNA支架和我们的合成系统具有高度的通用性，使我们能够制造出广泛的用户定义的肽和核苷酸序列组合，用于各种未来的生物医学和纳米技术应用。
Nucleic acids and proteins are the fundamental biopolymers that support all life on Earth. Nucleic acids store large amounts of information in nucleobase sequences while peptides and proteins utilize diverse amino acid functional groups to adopt complex structures and perform wide-ranging activities. Although nature has evolved machinery to read the nucleic acid code and translate it into amino acid code, the extant biopolymers are restricted to encoding amino acid or nucleotide sequences separately, limiting their potential applications in medicine and biotechnology. Here we describe the design, synthesis, and stimuli-responsive assembly behavior of a bilingual biopolymer that integrates both amino acid and nucleobase sequences into a single peptide nucleic acid (PNA) scaffold to enable tunable storage and retrieval of tertiary structural behavior and programmable molecular recognition capabilities. Incorporation of a defined sequence of amino acid side-chains along the PNA backbone yields amphiphiles having a "protein code" that directs self-assembly into micellar architectures in aqueous conditions. However, these amphiphiles also carry a "nucleotide code" such that subsequent introduction of a complementary RNA strand induces a sequence-specific disruption of assemblies through hybridization. Together, these properties establish bilingual PNA as a powerful biopolymer that combines two information systems to harness structural responsiveness and sequence recognition. The PNA scaffold and our synthetic system are highly generalizable, enabling fabrication of a wide array of user-defined peptide and nucleotide sequence combinations for diverse future biomedical and nanotechnology applications.