'Nearest-Neighbor Recognition in Lipid Bilayers'

“脂质双层中的最近邻识别”

• 批准号: 6752538
• 负责人: STEVEN L. REGEN
• 金额: $ 26.91万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752538
• 关键词: cholesterol; erythrocyte membrane; hydrogen bond; hydropathy; intermolecular interaction; lipid bilayer membrane; membrane activity; membrane biogenesis; membrane structure; phospholipids; sphingolipids

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.

本研究的总体目标是获得定量洞察脂质和脂质-蛋白质相互作用的流体双层状态，使用合成有机化学，物理有机化学和最近邻识别方法的组合。该计划的长期目标是发展对流体双层的二维组织的基本理解，这将有助于在生物膜中引入可利用的目标（例如，癌细胞、细菌细胞和真菌细胞的质膜）到更清晰的焦点。这种见解将有助于合理设计新型治疗药物。本资助期的具体目标包括：（1）利用最近邻识别方法绘制鞘脂/甘油磷脂/胆固醇和类似甘油磷脂/甘油磷脂/胆固醇双层的相图;（2）确定胆固醇相对于鞘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中的影响;（4）基于疏水匹配的磷脂的跨膜蛋白识别测试，（5）测量脂质跨膜-蛋白质相互作用对胆固醇存在的敏感性，（6）开发可用于研究相邻单层之间的脂质通讯的方法，和（7）检测相邻脂质的跨膜识别。