MASS SPECTROMETRY OF DRUGS, NATURAL PRODUCTS, PROTEINS, AND OLIGONUCLEOTIDES

药物、天然产物、蛋白质和寡核苷酸的质谱分析

• 批准号: 6432107
• 负责人: Lewis K. Pannell
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432107
• 关键词: aminoacid; antiviral agents; biological products; chemical information system; drug screening /evaluation; electrospray ionization mass spectrometry; marine biology; mass spectrometry; oligonucleotides; peptides; posttranslational modifications; stereoisomer; structural biology

Research of the unit is split between the identification of biologically active trace organic compounds isolated from natural sources and the mass spectrometry of biopolymers (e.g. peptide, proteins and oligonucleotides). A very close working relationship and collaboration is maintained with the Laboratory of Biophysical Chemistry, NHLBI. While this group runs many routine analyses for laboratories at NIH, as much emphasis as possible is placed on research using mass spectrometry for the structural elucidation of biologically active compounds. This year's key projects include: the structural identification of potent anti-HIV and anti-cancer compounds; the identification of post-translational modifications in proteins; continued research on cyanovirin, a potent anti-HIV compound heading towards clinical trial; development of techniques for micro- scale LCMS of biopolymers with the aim of greatly enhancing sensitivity; the identification and chiral determination of abnormal and modified amino acids as found in marine natural products; the identification of modified hemoglobins formed during treatments for sickle cell; and development of a method to follow protein folding using deuterium exchange. During the year the emphasis of all the research has become biopolymers and large proteins with multiple glycosylation sites and many overlapping disulfides and being examined. Attempts to define 3-D protein shapes using mass spectrometry are being developed. Multiple enzymatic digestion protocols and sophisticated software have been developed to assist the research and these are now in use worldwide. A new Q-TOF mass spectreometer shared with some other institutes has been ordered and this will drastically expand the biopolymer research potential of the group.

该单元的研究是在从天然来源分离出的生物活性痕量有机化合物的鉴定与生物聚合物的质谱（例如肽，蛋白质和寡核苷酸）的质谱。 NHLBI的生物物理化学实验室维持了非常紧密的工作关系和协作。尽管该组对NIH的实验室进行了许多常规分析，但尽可能多的重点是使用质谱法进行生物学活性化合物的结构阐明的研究。今年的主要项目包括：有效的抗HIV和抗癌化合物的结构鉴定；鉴定蛋白质的翻译后修饰；继续研究蓝藻（Cyanovirin），这是一种有效的抗HIV化合物，通向临床试验。开发生物聚合物微观LCM的技术，目的是极大地增强灵敏度；海洋天然产物中发现的异常和改良氨基酸的鉴定和手性测定；鉴定在治疗镰状细胞期间形成的改良血红蛋白；并开发了使用氘交换遵循蛋白质折叠的方法。 在这一年中，所有研究的重点已成为生物聚合物和大型蛋白质，具有多个糖基化位点以及许多重叠的二硫化物并被检查。 正在开发尝试使用质谱法定义3-D蛋白质形状的尝试。 已经开发了多种酶促消化方案和复杂的软件来协助研究，这些软件现已在全球使用。 已经订购了与其他一些机构共享的新的Q-TOF质谱仪，这将大大扩大该组的生物聚合物研究潜力。