Fluorescent Chemical Sensors for Bioactive Lipids

用于生物活性脂质的荧光化学传感器

• 批准号: 1507119
• 负责人: Timothy Glass
• 金额: $ 49.12万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507119&HistoricalAwards=false
• 关键词: Fluorescent; Chemical; Sensors; Bioactive; Lipids

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.

化学系的大分子、超分子和纳米化学项目获得该奖项，资助密苏里大学哥伦比亚分校的Timothy Glass教授为两种特定类别的脂质设计和合成分子传感器。脂类是一组具有多种生物功能的分子。许多脂质和含脂化合物除了作为动植物细胞膜和储能单元的结构成分外，还具有重要的生物活性，在人类各种疾病的发生发展中发挥着重要的作用。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对其进行治疗的方法。为了实现这一长期目标，格拉斯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，这些分子识别和结合特定类型的脂类，发出它们的存在信号，并从嵌入脂类分子的膜中提取它们。这一跨学科项目为研究生和本科生的研究性培养提供了一个极好的平台。此外，格拉斯教授通过为密苏里大学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。这些研究中的第一个目标脂类属于一种氧化磷脂，已被证明在动脉粥样硬化的发展中起着重要作用。第二类脂质称为糖脂，存在于许多细胞表面，参与癌症和炎症等各种过程。分子传感器由一个大的疏水裂隙(用于结合靶标脂质的疏水尾巴和信号转导)和某种类型的头基结合功能(用于识别靶标的头基)组成。对于氧化型磷脂传感器，使用肼与氧化型脂类的醛结合，从而为这种类型的脂类提供选择性。对于糖脂，基于硼酸的结合基团用于提供含糖脂的选择性。头基团结合部分被认为是一个足够的“钩”，允许受体从其包埋的膜中提取靶向脂质。然后，疏水裂隙包裹在脂类尾巴上。脂靶与分子传感器的结合有望导致荧光发射强度的变化，从而发出靶标存在的信号。