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

该单位的研究分为从天然来源分离的生物活性痕量有机化合物的鉴定和生物聚合物（例如肽，蛋白质和寡核苷酸）的质谱分析。一个非常密切的工作关系和合作是保持与生物物理化学实验室，NHLBI。虽然该小组为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进行生物活性化合物结构解析的研究。今年的重点项目包括：有效抗艾滋病病毒和抗癌化合物的结构鉴定;蛋白质翻译后修饰的鉴定;继续研究一种有效抗艾滋病病毒化合物cyanovirin的临床试验;开发生物聚合物的微型LCMS技术，以大大提高灵敏度;海洋天然产物中异常和修饰氨基酸的鉴定和手性测定;镰状细胞治疗过程中形成的修饰血红蛋白的鉴定;以及开发利用氘交换跟踪蛋白质折叠的方法。 在这一年中，所有研究的重点已经成为生物聚合物和具有多个糖基化位点和许多重叠二硫键的大蛋白质，并正在进行检查。 目前正在尝试使用质谱法来确定蛋白质的三维形状。 已经开发了多种酶消化方案和复杂的软件来协助研究，这些方案和软件现在在世界范围内使用。 与其他一些研究所共享的新Q-TOF质谱仪已被订购，这将大大扩大该集团的生物聚合物研究潜力。

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.