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: 2108538
• 负责人: Bing Gong
• 金额: $ 40万
• 依托单位: SUNY at Buffalo
• 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=2108538&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支持纽约州立大学布法罗州立大学Bing锣教授和Hofstra大学的Daniel P. Miller博士合成一系列“宿主”分子，并研究其对糖分子的结合和认识的亲和力。这项研究旨在更好地了解将导致与不同碳水化合物进行特定相互作用的因素，以便为未来的糖接收器和传感器设计提供指导原则。该协作项目将实验与理论研究相结合，并为本科生和研究生（包括代表性不足的学生的学生）提供了一个很好的平台。研究结果将纳入教学中，并将其广泛传播给科学界。宿主分子是具有可调长度的芳族寡酰胺折叠剂。寡酰胺折叠成螺旋线圈结构，有多个氢键受体针对纳米化的空心核。将螺旋线圈嵌入脂质双层膜中时，螺旋线圈堆叠以创建通道，通过该通道通过该通道从膜的一侧流到另一侧。在众多的H键位点，预计不同的糖和糖醇将与具有不同亲和力的螺旋线圈的内部孔相互作用。这种相互作用是动态和瞬态的，尤其是在水中，将通过跨膜孔扰动离子电流。该研究团队将（1）优化寡酰胺的合成，（2）执行一维核磁共振（NMR）光谱研究和X射线晶体学结构分析，以询问宿主和特定的碳氢化物之间的相互作用，以包括单糖，含糖，较高的含糖，以及较高的少含寡含糖。 （3）检查各种碳水化合物客人通过螺旋孔的跨膜离子电流的影响； （4）进行计算研究，以优化宿主 - 基因的结合，并探究碳水化合物客人对通过螺旋孔的跨膜离子流的影响。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响审查标准来通过评估来通过评估来支持的。

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