SOLUTION STRUCTURES OF ANTIMICROBIAL PEPTIDES

这项研究将生成有关解决方案的详细信息 一类新近发现的抗菌剂的结构 被称为防御素的多肽。这些多肽已经被分离出来 从兔、豚鼠和人的吞噬白细胞和 形成不依赖氧气的哺乳动物防御系统的一部分。这个 已鉴定的十种多肽具有较强的活性 对广泛的微生物，包括细菌，真菌和 被包裹的病毒。这些同源多肽都是半胱氨酸-和 富含精氨酸，长度29-34个残基，有8个保守的 整个家族的残留物。防御素在它们的 效力及其活动范围。它们的功能多样性 最有可能的原因是个体之间的结构差异 分子。这个项目将探索结构和动力学 以寻找相关性为目标的解决方案中的防御素 在结构的变化和不同的生物功能之间。 将用于确定结构的主要技术 防御素的主要成分是核磁共振波谱。 二维(2D)核Overhaser效应实验将 用于获得小于4.5的质子-质子核间距 埃斯特罗姆。额外的2D核磁共振实验将测量自旋 给出关于二面角的信息的耦合常数 分子。这个二面角和距离信息 用作距离几何计算的输入，该计算 生成溶液中分子的三维结构。 这一系列多肽还提供了理想的天然实验室 用于研究单个氨基酸的替代效应 关于多肽在溶液中的折叠、结构和动力学。 防御素家族的解决方案结构将提供 独一无二的探索分子特性的机会 了解这些多肽的生物学功能，可能会有所帮助 阐明它们在体内的作用机制。

This research will generate detailed information on the solution structures of a recently discovered family of antimicrobial peptides known as defensins. These peptides have been isolated from phagocytic leukocytes of rabbits, guinea pigs and humans and form part of the oxygen-independent mammalian defense system. The ten peptides that have been characterized posses potent activities against a broad spectrum of microbes including bacteria, fungi, and enveloped viruses. These homologous peptides are all cysteine- and arginine-rich, 29-34 residues in length and have 8 conserved residues in the whole family. The defensins vary greatly in their potency and their range of activities. Their functional diversity most likely arises from structural variations between individual molecules. This project will probe the structure and dynamics of the defensins in solution with goal of searching for correlations between variations in structure, and distinct biological function. The primary technique that will be used to determine the structure of defensins is nuclear magnetic resonance (NMR) spectroscopy. Two-dimensional (2D) nuclear Overhauser effect experiments will be used to obtain proton-proton internuclear distances less than 4.5 angstroms. Additional 2D NMR experiments will measure spin-spin coupling constants which give information on dihedral angles in the molecule. This dihedral angle and distance information then serves as the input for distance geometry calculations which generate three-dimensional structures of the molecules in solution. This family of peptides also provides an ideal natural laboratory for studying the effects of substitution of individual amino acids on the folding, structure, and dynamics of peptides in solution. The solution structures of the defensin family will provide a unique opportunity for probing the molecular properties that give rise to the biological function of these peptides and may help elucidate their mechanism of action in vivo.