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.

化学系高分子、超分子与纳米化学项目支持纽约州立大学布法罗分校龚兵教授和霍夫斯特拉大学Daniel P. Miller博士合成一系列“宿主”分子并研究其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。具有理论研究，并为本科生和研究生（包括代表性不足群体的学生）的研究培训提供了一个良好的平台，研究成果将被纳入教学并广泛传播给科学界。低聚酰胺折叠成螺旋线圈结构，多个氢键受体指向纳米尺寸的空心核，当嵌入水溶液中的脂质双层膜时，螺旋线圈堆叠形成离子和离子通过的通道。小分子从膜的一侧流向另一侧，不同的糖和糖醇预计会以不同的亲和力与螺旋线圈的内孔相互作用，这种相互作用是动态和瞬时的。尤其是在水中，会扰乱通过跨膜孔的离子电流。该研究小组将 (1) 优化低聚酰胺的合成，(2) 进行一维和二维核磁共振 (NMR) 波谱分析。研究和 X 射线晶体结构分析，以探究宿主与特定碳水化合物（包括单糖、二糖和高级寡糖）之间的相互作用；（3）检查各种碳水化合物客体对通过螺旋孔的跨膜离子电流的影响； 4) 进行研究以优化主客体结合并探测碳水化合物反映计算客体对穿过螺旋孔的跨膜离子流的影响。该奖项通过使用基金会的智力价值和更广泛的影响审查标准进行评估，NSF 的法定使命被认为值得支持。

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