Amphiphilic Peptide Nucleic Acids as Biostable Programmable Materials

非技术性：该奖项由材料研究部的生物材料项目授予犹他大学，表彰可用于药物和毒素检测或治疗药物受控输送的新型仿生材料的探索。核酸提供了异常丰富的信息架构，这种能力可以被利用在生物技术的各种应用中。然而，通常用于这些应用的分子不适合在生物环境中使用，因为它们会被酶迅速降解。这项提案将探索在生物环境中不会降解的非天然核酸。重要的是，这些核酸也可以被功能化，以赋予不同的化学性质。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，预计这将使治疗药物等小客体分子的结合和释放得到控制。这项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的培训经验。这个项目还将通过在PI讲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，来促进公众的科学素养。技术：本研究项目将探索两亲性多肽核酸(PNA)作为一种新的能够响应刺激的组装、拆卸和客人释放的可编程材料。PNA是一种人工核酸，具有独特的物理化学性质，这在很大程度上可以归因于它具有无手性、多肽样的骨架，而不是天然核酸中发现的糖-磷酸骨架。具体地说，PNA不被核酸酶或蛋白酶降解，并表现出与DNA和RNA的结合亲和力增加。此外，可以合成具有位于沿着主干的序列限定位置的功能多样化的侧链阵列的PNA。两亲性PNA链的合成和探索将被研究，其中侧链位于战略位置，以实现相驱动的自组装成胶束结构。具体地说，该项目将(1)建立两亲性PNA序列的组装和客体结合特性的设计规则；(2)评估PNA胶束对小分子和核酸靶标的分解和客体释放；(3)探索PNA两亲性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造福公众健康的潜力。

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.