Identification of peptide epimers in crystallin proteins

晶状体蛋白中肽差向异构体的鉴定

• 批准号: 8901229
• 负责人: Ryan Roy Julian
• 金额: $ 26.75万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8901229
• 关键词: Acids; Affect; Age; Age-Years; Aging; Alzheimer' s Disease; Amino Acids; Aspartic Acid; Automation; Blindness; Cataract; Collagen; Crystallins; Cysteine; Data Analyses; Dentin; Development; Disease; Dissociation; Eye Lens Protein; Funding; Generic Drugs; Goals; Handedness; Health; Human; Individual; Isoaspartic Acid; Isomerism; Lead; Life; Manuals; Mass Spectrum Analysis; Methods; Modification; Molecular; Molecular Chaperones; Motivation; Myopathy; Outcome; Oxidative Stress; Pathology; Peptides; Performance; Play; Post-Translational Protein Processing; Proteins; Proteomics; Protocols documentation; Research; Resolution; Role; Sampling; Site; Structure; Techniques; United States National Institutes of Health; Work; base; cost; disulfide bond; epimerization; extreme temperature; improved; innovation; insight; instrument; interest; lens; mass spectrometer; migration; prevent; programs; protein aggregation; protein degradation; protein structure; racemization; research study; scale up; tool

DESCRIPTION (provided by applicant): The overall goal of this project is to employ an innovative mass spectrometric technique to detect and characterize modifications to the chirality of individual amino acids within peptides and proteins. Chirality, or the handedness of a molecule, is a crucial attribute that influences both structure and function. Changes in chirality are very difficult to detect; however, a new method dependent on site specific radical migration is extremely sensitive to structure and can detect changes in chirality. The underlying motivation for performing this research is to investigate potential causes of cataract disease and to understand how protein modifications influence aging in general. Changes in chirality have been examined in primarily a generic sense in eye lens proteins previously, and these changes have been noted to increase for cataractous lenses. Site-specific examination of changes in chirality has not been carried out previously because no suitable tool was available for performing the task. The outcome of this project will be detailed information that elucidates how chiral inversion contributes to cataract formation and to aging in general, which is necessary to guide the development of potential preventative treatments.

描述（由申请人提供）：该项目的总体目标是采用创新的质谱技术来检测和表征肽和蛋白质内单个氨基酸的手性修饰。手性或分子的旋向性是影响结构和功能的关键属性。手性的变化很难被检测到；然而，一种依赖于位点特异性自由基迁移的新方法对结构极其敏感，并且可以检测手性的变化。进行这项研究的根本动机是调查白内障疾病的潜在原因，并了解蛋白质修饰如何影响衰老。此前，人们主要在一般意义上对眼晶状体蛋白的手性变化进行了研究，并且已经注意到这些变化对于白内障晶状体来说会增加。之前尚未对手性变化进行现场特定检查，因为没有合适的工具可用于执行该任务。该项目的成果将是阐明手性反转如何进行的详细信息 一般而言，它会导致白内障的形成和衰老，这对于指导潜在预防治疗的开发是必要的。