Collaborative Research: Understanding the Molecular Recognition Behavior of Hollow Helices

合作研究：了解空心螺旋的分子识别行为

• 批准号: 2108597
• 负责人: Daniel Miller
• 金额: $ 8万
• 依托单位: Hofstra 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: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108597&HistoricalAwards=false
• 关键词: Collaborative; Research; Understanding; Molecular; Recognition

The Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is supporting Professor Bing Gong of the State University of New York at Buffalo and Dr. Daniel P. Miller of the Hofstra University to synthesize a series of “host” molecules and investigate their affinity for binding and recognition of sugar molecules. This research aims to gain a better understanding of the factors that will lead to specific interactions with different carbohydrates in order to provide guiding principles for future design of sugar receptors and sensors. This collaborative project integrates experiments with theoretical studies and provides a great platform for research training of undergraduate and graduate students, including students of underrepresented groups. The research results will be incorporated into teaching and broadly disseminated to the scientific community. The host molecules are aromatic oligoamide foldamers with tunable lengths. The oligoamides fold into helical coil structures with multiple hydrogen bond acceptors being directed toward the nanosized hollow core. When embedded in a lipid bilayer membrane in aqueous solution, the helical coils stack to create channels through which ions and small molecules flow from one side of the membrane to the other side. With the numerous H-bonding sites, different sugars and sugar alcohols are expected to interact with the inner pore of the helical coil with different affinities. Such interaction, being dynamic and transient, especially in water, will perturb the ion currents through the transmembrane pores. This research team will (1) optimize the synthesis of the oligoamides, (2) perform one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopic studies and X-ray crystallographic structural analysis to interrogate the interactions between the host and specific carbohydrates to include monosaccharides, disaccharides, and higher oligosaccharides; (3) examine the effects of various carbohydrate guests on the transmembrane ion currents through the helical pores; and (4) carry out computational studies to optimize host-guest binding and to probe the effect carbohydrate guests have on transmembrane ion flows through the helical pores.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.

化学系的大分子、超分子和纳米化学计划正在支持纽约州立大学布法罗分校的龚兵教授和霍夫斯特拉大学的丹尼尔·P·米勒博士合成一系列“宿主”分子，并研究它们对糖分子的结合和识别的亲和力。这项研究旨在更好地了解导致与不同碳水化合物发生特定相互作用的因素，以便为未来糖受体和传感器的设计提供指导原则。这个合作项目将实验和理论研究结合在一起，为本科生和研究生，包括代表不足群体的学生提供了一个很好的研究培训平台。研究成果将纳入教学并广泛传播给科学界。主体分子是长度可调的芳香族寡酰胺折叠体。寡酰胺折叠成螺旋卷曲结构，多个氢键受体指向纳米级的中空核心。当嵌入到水溶液中的脂质双层膜中时，螺旋线圈堆叠起来形成通道，离子和小分子通过这些通道从膜的一侧流向另一侧。由于存在大量的氢键，不同的糖和糖醇有望以不同的亲和力与螺旋线圈的内孔相互作用。这种动态和瞬时的相互作用，特别是在水中，将扰乱通过跨膜毛孔的离子电流。该研究小组将(1)优化低聚糖的合成，(2)进行一维和二维核磁共振波谱研究和X射线晶体结构分析，以询问宿主与特定碳水化合物之间的相互作用，包括单糖、双糖和高级低聚糖；(3)考察不同碳水化合物客体对穿过螺旋孔的跨膜离子电流的影响；以及(4)开展计算研究，以优化主-客结合，并探索碳水化合物客人对通过螺旋孔的跨膜离子流动的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ultra‐Tight Host‐Guest Binding with Exceptionally Strong Positive Cooperativity

超紧主客绑定，正协同性极强

• DOI: 10.1002/anie.202213467
• 发表时间: 2022
• 期刊: Angewandte Chemie International Edition
• 作者: Sobiech, Thomas A.;Zhong, Yulong;Miller, Daniel P.;McGrath, Jillian K.;Scalzo, Christina T.;Redington, Morgan C.;Zurek, Eva;Gong, Bing
• 通讯作者: Gong, Bing

Stable pseudo[3]rotaxanes with strong positive binding cooperativity based on shape-persistent aromatic oligoamide macrocycles

基于形状持久的芳香低聚酰胺大环，具有强正结合协同性的稳定假[3]轮烷

• DOI: 10.1039/d1cc05193h
• 发表时间: 2021
• 期刊: Chemical Communications
• 影响因子: 4.9
• 作者: Sobiech, Thomas A.;Zhong, Yulong;Sánchez B., Laura S.;Kauffmann, Brice;McGrath, Jillian K.;Scalzo, Christina;Miller, Daniel P.;Huc, Ivan;Zurek, Eva;Ferrand, Yann
• 通讯作者: Ferrand, Yann