Cyclodextrin Derivatives as Protein Folding Aids

作为蛋白质折叠助剂的环糊精衍生物

• 批准号: 6504728
• 负责人: AJIT SHARMA
• 金额: $ 13.53万
• 依托单位: CENTRAL MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6504728
• 关键词: chemical aggregate; cyclodextrins; molecular chaperones; protein folding; protein structure function

DESCRIPTION (provided by applicant): Protein aggregation is a serious problem in the production of recombinant proteins as well as in many neurodegenerative diseases. The principal investigator was the first to demonstrate the ability of cyclic polysaccharides known as cyclodextrins (CDs) to act as "mini-chaperones" in protein folding. Cyclodextrins bind to polypeptide chains during the folding process. This prevents aggregation and promotes the folding of the protein to form its native structure. The nature of the complex and rapidly changing interactions between the folding protein and the cyclodextrins is unclear. The major objective of this proposal is to study if and how selective chemical modifications of cyclodextrin affect protein aggregation. Beta-cyclodextrin derivatives of various size, charge, functional groups and architecture will be synthesized. Structure-activity relationships between cyclodextrin chemistry and chaperone activity will be established. These studies should provide invaluable data towards a rational design and synthesis of a CD derivative with ideal anti-protein aggregation properties. Results from the proposed study will help understand the mechanisms of interactions of these cyclic oligosaccharides with unfolded, folding and folded polypeptide chains formed during protein folding. This information will be of benefit toward an understanding of in vitro and in vivo protein aggregation.

描述（由申请人提供）：蛋白质聚集是重组蛋白生产以及许多神经退行性疾病中的严重问题。首席研究员是第一个证明被称为环糊精（CD）的环状多糖在蛋白质折叠中充当“迷你伴侣”的能力。环糊精在折叠过程中与多肽链结合。这防止聚集并促进蛋白质折叠以形成其天然结构。折叠蛋白质和环糊精之间复杂和快速变化的相互作用的性质尚不清楚。该提案的主要目的是研究环糊精的选择性化学修饰是否以及如何影响蛋白质聚集。将合成各种尺寸、电荷、官能团和结构的β-环糊精衍生物。将建立环糊精化学和分子伴侣活性之间的结构-活性关系。这些研究将为合理设计和合成具有理想抗蛋白聚集特性的CD衍生物提供宝贵的数据。从拟议的研究结果将有助于了解这些环状寡糖与蛋白质折叠过程中形成的未折叠，折叠和折叠的多肽链的相互作用机制。这一信息将有利于在体外和体内蛋白质聚集的理解。