Fluorescent Chemical Sensors for Bioactive Lipids

化学系的大分子、超分子和纳米化学项目将资助密苏里-哥伦比亚大学的Timothy Glass教授设计和合成两种特定类型脂质的分子传感器。脂质是一组具有多种生物功能的分子。许多脂类和含脂化合物除了作为植物和动物细胞膜的结构成分和能量储存单位外，还具有重要的生物活性，在人类各种疾病的发生发展中起着重要作用。因此，检测特定类型脂质的能力提供了一种检测疾病并在某些情况下治疗疾病的方法。为了实现这一长期目标，Glass教授进行了基础研究，以更好地了解脂质和合成受体之间的相互作用。他的研究旨在为设计有机分子提供指导原则，这些有机分子可以识别和结合特定类型的脂质，发出它们的存在信号，并从脂质分子嵌入的膜中提取它们。这个跨学科的项目为研究生和本科生的研究训练提供了一个很好的平台。此外，格拉斯教授还为密苏里大学（University of Missouri）为高中教师和学生举办的暑期项目开发内容，向公众推广科学。这些研究的第一个目标脂质属于一类氧化磷脂，已被证明在动脉粥样硬化的发展中很重要。第二类脂质被称为糖脂，存在于许多细胞表面，并参与各种过程，如癌症和炎症。分子传感器由一个大的疏水间隙（用于结合目标脂质的疏水尾部和信号转导）和某种类型的头基团结合功能（用于识别目标的头基团）组成。对于氧化磷脂传感器，使用联氨与氧化脂质的醛结合，为这种类型的脂质提供选择性。对于糖脂，硼酸基结合基团用于对含糖脂提供选择性。头部基团结合部分预计是一个足够的“钩子”，允许受体从其所嵌入的膜中提取目标脂质。疏水裂缝然后包裹在脂质尾部。脂质靶标与分子传感器的结合预计会导致荧光发射强度的变化，表明靶标的存在。

With this award, the Macromolecular, Supramolecular, and Nanochemistry Program of the Division of Chemistry is funding Professor Timothy Glass of the University of Missouri-Columbia to design and synthesize molecular sensors for two specific classes of lipids. Lipids are a diverse group of molecules with a variety of biological functions. In addition to serving as the structural components of cell membranes and energy storage units in plants and animals, many lipids and lipid-containing compounds possess important biological activities and play significant roles in the development of various human diseases. Therefore, the ability to detect specific types of lipids provides a method to detect the diseases and in some cases treat them. Towards this long term goal, Prof. Glass conducts fundamental studies to gain a better understanding of the interactions between lipids and synthetic receptors. His research aims to provide guiding principles for designing organic molecules that recognize and bind specific types of lipids, signal their presence, and extract them from a membrane in which the lipid molecules are embedded in. This interdisciplinary project provides an excellent platform for research training of graduate and undergraduate students. In addition, Prof. Glass promotes science to the general public by developing content for a summer program to be held at the University of Missouri for high school teachers and students.The first lipid targeted in these studies belongs to a class of oxidized phospholipid that has been shown to be important in the development of atherosclerosis. The second class of lipids, called glycolipids, are found on many cell surfaces and are involved in various processes such as cancer and inflammation. The molecular sensor is composed of a large hydrophobic cleft (for binding the hydrophobic tail of the target lipid and signal transduction) with some type of head-group binding functionality (for recognition of the head group of the target). For the oxidized phospholipid sensors, a hydrazine is used to bind to an aldehyde of the oxidized lipid providing selectivity for just this type of lipid. For the glycolipids, a boronic acid-based binding group is used to provide selectivity for sugar-containing lipids. The head-group binding moiety is anticipated to be a sufficient "hook" to allow the receptor to extract the target lipid from the membrane in which it is embedded. The hydrophobic cleft then wraps around the lipid tail. The binding of the lipid target to the molecular sensor is expected to result in change in fluorescence emission intensity, signaling the presence of the target.