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: 6289766
• 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/6289766
• 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 years 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. Work has expanded into large proteins with multiple glycosylation sites and many overlapping disulfides. Multiple enzymatic digestion protocols and sophisticated software have been developed to solve these problems. A collaboration continues with The National Institute of Standards and Technology (NIST) involving the measurement of mass spectra of organic compounds from NIH, the Walter Reed Army Institute of Research and other government agencies. These are then put into the NIST/EPA/NIH mass spectral database which is in use world wide. - mass spectrometry, proteins, disulfides, glycosylation, electrospray, natural products, anti-HIV, sickle cell anemia

该单位的研究分为从天然来源分离的生物活性微量有机化合物的鉴定和生物聚合物（如肽，蛋白质和寡核苷酸）的质谱分析。与NHLBI生物物理化学实验室保持着非常密切的工作关系和合作。虽然这个小组为NIH的实验室进行了许多常规分析，但尽可能多地强调使用质谱法研究生物活性化合物的结构。今年的重点项目包括：强效抗艾滋病和抗癌化合物的结构鉴定；蛋白质翻译后修饰的鉴定；继续研究强效抗艾滋病毒化合物氰维林（cyanovirin），该药物即将进入临床试验阶段；发展生物聚合物的微尺度LCMS技术，以期大大提高灵敏度；海洋天然产物中异常氨基酸和修饰氨基酸的鉴定及手性测定镰状细胞治疗过程中形成的修饰血红蛋白的鉴定。工作已经扩展到具有多个糖基化位点和许多重叠二硫化物的大型蛋白质。多种酶消化方案和复杂的软件已经开发出来解决这些问题。与美国国家标准与技术研究所（NIST）的合作仍在继续，涉及来自美国国立卫生研究院、沃尔特里德陆军研究所和其他政府机构的有机化合物的质谱测量。然后将这些数据输入NIST/EPA/NIH的质谱数据库，该数据库在世界范围内使用。-质谱，蛋白质，二硫化物，糖基化，电喷雾，天然产物，抗hiv，镰状细胞性贫血