AMYLOID FORMATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 来自罗利公司的网站： 在某些疾病中，通常可溶的蛋白质聚集在一起形成一种密集的结构，称为淀粉样原纤维。在II型糖尿病、阿尔茨海默病患者和接受肾脏透析的患者中，都存在淀粉样沉积。人们对淀粉样蛋白形成的分子机制知之甚少。我们正在研究淀粉蛋白和降钙素多肽形成淀粉样蛋白的过程。淀粉是一种37个残基的多肽，在II型糖尿病中形成淀粉样蛋白沉积，而降钙素在甲状腺中形成淀粉样蛋白沉积。我们的工作包括通过固相多肽合成制备多肽，这些分子结构的特征以及淀粉样蛋白形成的动力学研究。 我们正在使用天然MS来确定胰淀素多肽的多聚体化学计量比随时间的变化。将这些信息与罗利实验室获得的动力学和毒性数据结合起来，应该可以提供关于哪些聚合体大小对胰淀素聚集的毒性特性负责的有价值的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. From the Raleigh web site: "In certain diseases normally soluble proteins aggregate to form a dense structure called the amyloid fibril. Amyloid deposits are present in individuals suffering from type-II diabetes, Alzheimer's disease and in patients undergoing kidney dialysis. Little is known about the molecular mechanism of amyloid formation. We are studying amyloid formation by the polypeptides amylin and calcitonin. Amylinis a 37 residue peptide which forms amyloid deposits in type-II diabetes while calcitonin forms amyloid deposits in the thyroid. Our work involves the preparation of the peptides via solid phase peptide synthesis, the characterization of the structure of these molecules and studies of the kinetics of amyloid formation." We are using native MS to determine what multimeric stoichiometries of an Amylin peptide are present as a function of time. Coupling this information to kinetic and toxicity data obtained by the Raleigh lab should provide valuable insights regarding which mer sizes are responsible for the toxic properties of Amylin aggregation.