NMR-spektroskopische Untersuchungen der membranmodifizierenden Eigenschaften polyphiler Moleküle: Struktur und Lipiddynamik

本子项目的目标是对在其他基团子项目中合成的多亲分子的膜修饰特性进行全面的核磁共振光谱表征，并通过互补技术在Blume和Bacia基团中进行研究。由于其化学区域选择性，固态核磁共振比任何其他方法都更适合于在分子基础上阐明膜修饰性质的起源。在第一个资助期，我们主要从事方法开发，对不同的核磁共振方法进行概念性测试，扩大其应用范围和已知的局限性，并初步了解相互作用机制。我们已经建立了一些方法，一方面(i)通过测量偶极-偶极耦合和交叉弛豫/自旋扩散来报告膜上或膜内客体分子的结构排列，另一方面（ii）报告膜性质的变化，如刚度、孔隙度或缺陷含量。对于后者，脂链中CH偶极-偶极耦合的测量、层间水的静态2H光谱、通过膜传输的扩散测量以及通过31P化学位移各向异性对头基团重定向动力学的研究已被证明是有用的。然而，在某些情况下，由于部分矛盾和不完整的文献数据，我们认为需要进一步发展方法。所研究的一部分多亲体被证明仅具有表面活性，即小片层碎片（双束）通过横向相互作用稳定，并且未检测到脂质分子动力学性质的变化。具有明显膜修饰特性的膜溶性多亲物仅在本报告所述期间末可用，目前正在进行全面研究。第一个有趣的结果出现在项目报告中

The goal of this subproject is the comprehensive NMR-spectroscopic characterization of the membrane-modifying properties of polyphilic molecules which are synthesized in the subprojects of the other groups, and which are studied by complementary techniques in the groups of Blume and Bacia. Due to its chemical regio-selectivity, solid-state NMR, more than any other method, is well suited to clarify the origins of membrane-modifying properties on a molecular basis. In the first funding period, we were mainly occupied with methodological developments, subjecting different NMR methods to conceptual tests and widening their application range and the known limitations, and gained first insights into the interaction mechanisms. We have established methods that report on the one hand (i) on the structural arrangement of guest molecules at or in the membrane via the measurement of dipole-dipole couplings and cross relaxation/spin diffusion, and on the other hand (ii) on changes of the membrane properties such as stiffness, porosity, or defect content. For the latter, measurements of CH dipole-dipole couplings in the lipid chains, static 2H spectra of the interlamellar water, diffusion measurements of the through-membrane transport, and studies of the reorientation dynamics of the head groups via the 31P chemical shift anisotropy have proven useful. However in some cases, owing to partially contradictory and incomplete literature data, we see a further need for methodological development. A part of the studied polyphiles turned out to be merely surface active, i.e., small lamellar fragments (bicelles) were stabilized by lateral interactions and no changes in the molecular dynamic properties of the lipids were detected. Membrane-soluble polyphiles with distinct membrane-modifying properties were available only by the end of the period under report, and are currently subjected to a comprehensive study. First interesting results are presented in the project report