Amphiphilic Peptide Nucleic Acids as Biostable Programmable Materials

两亲性肽核酸作为生物稳定可编程材料

• 批准号: 1709208
• 负责人: Jennifer Heemstra
• 金额: $ 39万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709208&HistoricalAwards=false
• 关键词: Amphiphilic; Peptide; Nucleic; Acids; Biostable

Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Utah is for exploration of new biomimetic materials that can be used for applications in the detection of drugs and toxins, or for the controlled delivery of therapeutics. Nucleic acids provide exceptionally information-rich architectures, and this capability can be harnessed for a variety of applications in biotechnology. However, the molecules typically used in these applications are not suitable for use in biological environments, as they are rapidly degraded by enzymes. This proposal will explore non-natural nucleic acids that are not degraded in biological environments. Importantly, these nucleic acids can also be functionalized to impart a diverse range of chemical properties. In the proposed research, the modulation of these properties will be explored to control formation and disruption of nanoscale assemblies, which is anticipated to enable controlled binding and release of small guest molecules such as therapeutics. This research project will span the fields of materials science, chemistry, and molecular biology, providing undergraduate and graduate students with a highly interdisciplinary training experience involving the use of cutting edge techniques. This project will also contribute to public scientific literacy through a blog project implemented in a course taught by the PI, as well as through the PI's participation as a judge and student mentor for the high school International Science Fair.Technical: This research project will explore amphiphilic peptide nucleic acids (PNA) as a new class of programmable materials capable of stimuli-responsive assembly, disassembly, and guest release. PNA is an artificial nucleic acid having unique physicochemical properties, which can largely be attributed to the fact that it has an achiral, peptide-like backbone in place of the sugar-phosphate backbone found in native nucleic acids. Specifically, PNA is not degraded by nucleases or proteases, and exhibits increased binding affinity with DNA and RNA. Additionally, PNA can be synthesized having a functionally diverse array of side chains located at sequence-defined positions along the backbone. Synthesis and exploration of amphiphilic PNA strands in which side chains are strategically located to enable phase-driven self-assembly into micellar architectures will be studied. Specifically, the project will (1) establish design rules for the assembly and guest binding properties of amphiphilic PNA sequences; (2) evaluate disassembly and guest release from PNA micelles in response to small-molecule and nucleic acid targets; (3) explore stimuli-responsive assembly of PNA amphiphiles to promote small-molecule release. The broader impacts of the proposed research include activities aimed at improving undergraduate education and public scientific literacy, and the potential to benefit public health through the future development of improved diagnostics and drug delivery platforms.

非技术性：该奖项由犹他州大学材料研究部生物材料项目授予，旨在探索可用于药物和毒素检测或治疗药物控制输送的新型仿生材料。 核酸提供了异常丰富的信息结构，这种能力可以用于生物技术中的各种应用。 然而，通常用于这些应用的分子不适合用于生物环境，因为它们被酶快速降解。该提案将探索在生物环境中不降解的非天然核酸。 重要的是，这些核酸也可以被官能化以赋予不同范围的化学性质。 在拟议的研究中，将探索这些性质的调节，以控制纳米级组件的形成和破坏，预计这将使小客体分子（如治疗剂）的结合和释放受到控制。 该研究项目将跨越材料科学，化学和分子生物学领域，为本科生和研究生提供涉及使用尖端技术的高度跨学科培训经验。 该项目还将通过在PI教授的课程中实施的博客项目以及PI作为高中国际科学博览会的评委和学生导师的参与，为公众的科学素养做出贡献。技术：该研究项目将探索两亲性肽核酸（PNA）作为一类新的可编程材料，能够刺激响应组装，拆卸和客人释放。 PNA是一种具有独特物理化学性质的人工核酸，这在很大程度上归因于它具有非手性的肽样骨架代替天然核酸中发现的糖-磷酸骨架的事实。 具体地，PNA不被核酸酶或蛋白酶降解，并且表现出与DNA和RNA的结合亲和力增加。 另外，可以合成具有位于沿主链沿着的序列限定的位置处的功能多样的侧链阵列的PNA。 将研究两亲性PNA链的合成和探索，其中侧链被战略性地定位以使相驱动的自组装成胶束结构。 具体而言，该项目将（1）建立两亲性PNA序列组装和客体结合特性的设计规则;（2）评估PNA胶束响应小分子和核酸靶标的拆卸和客体释放;（3）探索PNA两亲物的刺激响应组装以促进小分子释放。 拟议研究的更广泛影响包括旨在改善本科生教育和公众科学素养的活动，以及通过未来开发改进的诊断和药物输送平台来造福公众健康的潜力。