'Nearest-Neighbor Recognition in Lipid Bilayers'

这项研究的总体目标是利用合成有机化学、物理有机化学和最近邻识别方法相结合的方法，定量地了解流体双层状态下的脂类和脂类-蛋白质的相互作用。该计划的长期目标是对流体双层的二维组织有一个基本的了解，这将有助于使生物膜(例如，癌细胞、细菌细胞和真菌细胞的质膜)中的可利用靶标得到更清晰的关注。这种洞察力将有助于合理设计新型治疗剂。当前资助期的具体目标包括：(1)利用最近邻识别方法绘制鞘磷脂/甘油磷脂/胆固醇和类似glycerophospholipid/glycerophospholipid/cholesterol，双层的相图；(2)确定胆固醇相对于鞘磷脂和甘油磷脂的最近邻偏好；(3)确定碳水化合物头部基团在促进自聚集方面的影响；(4)基于疏水匹配的磷脂跨膜-蛋白质识别测试，(5)测量脂类跨膜-蛋白质相互作用对胆固醇存在的敏感性，(6)发展一种可用于研究相邻单层之间脂类通讯的方法学，以及(7)检测相邻脂类的跨膜识别。

The overall objective of this research is to gain quantitative insight into lipid lipid and lipid-protein interactions in the fluid bilayer state, using a combination of synthetic-organic chemistry, physical-organic chemistry, and the nearest-neighbor recognition method. The long-term goal of this program is to develop a fundamental understanding of the two- dimensional organization of fluid bilayers, which will help to bring exploitable targets in biological membranes (e.g., the plasma membrane of cancer cells, bacterial cells, and fungal cells) into sharper focus. Such insight will assist the rational design of novel classes of therapeutic agents. The specific aims of the current funding period include: (1) mapping out phase diagrams of sphingolipid/glycerophospholipid/cholesterol, and analogous glycerophospholipid/glycerophospholipid/cholesterol, bilayers by use of nearest-neighbor recognition methods; (2) defining the nearest-neighbor preference of cholesterol with respect to a sphingolipid and a glycerophospholipid; (3) defining the influence of a carbohydrate head group in promoting self-aggregation; (4) testing for transmembrane-protein recognition of a phospholipid based on hydrophobic matching, (5) measuring the sensitivity of lipid transmembrane-protein interactions toward the presence of cholesterol, (6) developing a methodology that can be used to study lipid communication between adjoining monolayers, and (7) detecting transmembrane recognition of neighboring lipids.