Sequence Programmable Triazine-Thymine Synthetic Ligands

序列可编程三嗪-胸腺嘧啶合成配体

• 批准号: 2105834
• 负责人: Christopher Alabi
• 金额: $ 48.62万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2105834&HistoricalAwards=false
• 关键词: Sequence; Programmable; Triazine; Thymine; Synthetic

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Christopher Alabi of Cornell University will design a chemical platform that can be programmed with multiple "sticky" side chains to create complementary pairs of chains similar to double-stranded DNA, that are able to assemble in the absence of water. A physical analogy is a beaded necklace with black and white beads that can bind to each other but not to themselves (i.e., black binds white but not black). Thus, the ability of a necklace with both black and white beads to stick to another beaded necklace will depend on the number of each type of beads in the necklace, the length of the necklace, and the positions of the black and white beads in each necklace. This work aims to design such a system on a molecular scale where the "sticky" black and white beads are molecules referred to as diaminotriazine and thymine, respectively. Mastering the design of these "sticky" chains that can undergo specific pairing in non-aqueous environment has the potential to open up new and exciting opportunities in the design and assembly of new functional materials. Educational and outreach activities will be integrated throughout this research project through a common theme that is focused on promoting peer-to-peer learning and empowering young aspiring scientists to take up leadership positions in communicating STEM (science, technology, engineering and mathematics) ideas to the broader public. Overall, the proposed project is expected to create new knowledge on how the composition and ordering of "sticky" building blocks along a polymer chain affects their ability to form selective molecular "velcros" that can be used in functional materials assembly. The central goal of this proposal is to design a programmable oligomer platform with molecular recognition motifs that can be used to encode information for hybridization in non-aqueous media. To design synthetic programmable ligands, the scalable sequence-defined oligocarbamate (SeDOC) platform will be exploited with diaminotriazine and thymine pendant binding motifs that dictate sequence, solubility, and hybridization strength. The proposed programmable SeDOC ligands will be designed to be soluble in organic solvents without the need for any additional reagents. Similar to DNA (2'-deoxyribonucleic acid), the number of interacting pendant motifs and length of the SeDOC backbone will define the coding space (i.e., sequence). However, unlike DNA, only a few binding motifs will be required for strong hybridization (as seen experimentally in a high Ka = high equilibrium association constant) due to the absence of a repulsive anionic backbone and the strong binding affinity of the diaminotriazine-thymine interaction in aprotic organic solvents. The proposal will investigate the effect of pendant group composition and sequence on hybridization strength toward the design of selective pairs of complementary SeDOC strands that can be used as ligands in various materials science applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系大分子，超分子和纳米化学项目的支持下，康奈尔大学的Christopher Rupi将设计一个化学平台，该平台可以用多个“粘性”侧链进行编程，以创建类似于双链DNA的互补链对，能够在没有水的情况下组装。一个物理类比是一条珠子项链，上面有黑色和白色珠子，它们可以相互结合，但不能相互结合（即，黑与白色结合，而不是黑）。因此，具有黑色和白色珠子的项链粘附到另一个串珠项链的能力将取决于项链中每种类型珠子的数量、项链的长度以及每条项链中黑色和白色珠子的位置。这项工作的目的是在分子尺度上设计这样一个系统，其中“粘性”黑色和白色珠子分别是被称为二氨基三嗪和胸腺嘧啶的分子。掌握这些可以在非水环境中进行特定配对的“粘性”链的设计有可能在新功能材料的设计和组装中开辟新的和令人兴奋的机会。教育和外联活动将通过一个共同的主题贯穿整个研究项目，该主题侧重于促进同行之间的学习，并使有抱负的年轻科学家能够在向更广泛的公众传播STEM（科学，技术，工程和数学）思想方面担任领导职务。总的来说，拟议的项目预计将创造新的知识，如何组成和排序的“粘性”积木沿着一个聚合物链影响他们的能力，形成选择性的分子“维可牢尼龙搭扣”，可用于功能材料组装。该提案的中心目标是设计具有分子识别基序的可编程寡聚物平台，其可用于编码非水介质中的杂交信息。为了设计合成的可编程配体，可扩展的序列定义的寡聚氨基甲酸酯（SeDOC）平台将利用二氨基三嗪和胸腺嘧啶侧基结合基序，决定序列，溶解度和杂交强度。所提出的可编程SeDOC配体将被设计为可溶于有机溶剂，而不需要任何额外的试剂。类似于DNA（2 '-脱氧核糖核酸），相互作用的侧基序的数量和SeDOC主链的长度将限定编码空间（即，序列）。然而，与DNA不同，由于不存在排斥性阴离子骨架和非质子有机溶剂中二氨基三嗪-胸腺嘧啶相互作用的强结合亲和力，强杂交仅需要几个结合基序（如实验中在高Ka =高平衡缔合常数中所见）。该提案将调查侧基组成和序列对杂交强度的影响，以设计可用作各种材料科学应用中配体的选择性互补SeDOC链对。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。