Fluorescent Chemical Sensors for Bioactive Lipids

有了这个奖项，化学系的大分子，超分子和纳米化学项目资助密苏里大学哥伦比亚分校的蒂莫西·格拉斯教授设计和合成两种特定类型脂质的分子传感器。脂质是具有多种生物学功能的一组不同的分子。 除了作为植物和动物细胞膜和能量储存单元的结构组分外，许多脂质和含脂质化合物具有重要的生物活性，并在各种人类疾病的发展中发挥重要作用。 因此，检测特定类型脂质的能力提供了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，这些有机分子识别和结合特定类型的脂质，发出它们存在的信号，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培训提供了一个很好的平台。 此外，Glass教授还为即将在密苏里州大学举办的面向高中教师和学生的暑期项目开发内容，向公众推广科学。这些研究中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。 分子传感器由具有某种类型的头基结合功能（用于识别目标的头基）的大疏水裂缝（用于结合目标脂质的疏水尾部和信号转导）组成。 对于氧化磷脂传感器，肼用于结合氧化脂质的醛，从而仅提供对这种类型脂质的选择性。对于糖脂，使用基于硼酸的结合基团来提供对含糖脂质的选择性。 预期头基结合部分是足够的“钩”，以允许受体从其嵌入的膜中提取靶脂质。 疏水裂缝然后缠绕在脂质尾部周围。 预期脂质靶标与分子传感器的结合会导致荧光发射强度的变化，从而发出靶标存在的信号。

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.