SOLUTION STRUCTURES OF ANTIMICROBIAL PEPTIDES

此研究将生成有关解决方案的详细信息 最近发现的一个抗菌家族的结构 称为防御素的肽。 这些肽已经被分离出来 来自兔子、豚鼠和人类的吞噬白细胞， 构成不依赖氧气的哺乳动物防御系统的一部分。 的 十种具有抗肿瘤活性的肽 针对广谱微生物，包括细菌、真菌和 包膜病毒 这些同源肽都是半胱氨酸， 富含丝氨酸，长度为29-34个残基，具有8个保守的氨基酸残基， 残留在整个家庭。 防御素在它们的 的能力和活动范围。 其功能多样性 最有可能是由于个体之间的结构差异 分子。 该项目将探讨的结构和动力学 在溶液中的防御素， 在结构的变化和不同的生物功能之间。 用于确定结构的主要技术 是核磁共振（NMR）光谱。 二维（2D）核Overhauser效应实验将在 用于获得质子-质子核间距小于4.5 埃。 额外的2D NMR实验将测量自旋-自旋 耦合常数给出二面角的信息， 分子。 这个二面角和距离信息 用作距离几何计算的输入， 在溶液中生成分子的三维结构。 这个肽家族也提供了一个理想的天然实验室 用于研究单个氨基酸取代的影响 关于溶液中肽的折叠、结构和动力学。 防御素家族的解决方案结构将提供一个 这是一个独特的机会，可以探测 提升这些肽的生物学功能， 阐明其在体内的作用机制。

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.