Collaborative Research: Understanding the Molecular Recognition Behavior of Hollow Helices

化学系的大分子、超分子和纳米化学项目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Daniel P. Miller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。本研究旨在更好地了解导致与不同碳水化合物特定相互作用的因素，以便为未来设计糖受体和传感器提供指导原则。该合作项目将实验与理论研究相结合，为本科生和研究生，包括代表性不足群体的学生提供了一个很好的研究训练平台。研究成果将纳入教学，并广泛传播给科学界。宿主分子是长度可调的芳香低聚酰胺折叠体。低聚酰胺折叠成螺旋线圈结构，多个氢键受体指向纳米级空心核心。当在水溶液中嵌入脂质双层膜时，螺旋线圈堆叠形成通道，离子和小分子通过通道从膜的一侧流向另一侧。由于有大量的氢键位点，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。这种相互作用是动态的和短暂的，特别是在水中，会扰乱通过跨膜孔的离子流。本研究团队将(1)优化低聚酰胺的合成，(2)进行一维和二维核磁共振（NMR）光谱研究和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、双糖和高级低聚糖）之间的相互作用；(3)考察不同碳水化合物客体对螺旋孔跨膜离子电流的影响；(4)进行计算研究，优化主-客体结合，探索碳水化合物客体对螺旋孔跨膜离子流动的影响。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。

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.