XAFS STUDIES OF BIOINORGANIC SYSTEMS

生物无机系统的 XAFS 研究

• 批准号: 7597959
• 负责人: PETER A LAY
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7597959
• 关键词: Adverse effects; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Binding; Biological Process; Cell Death; Complex; Computer Retrieval of Information on Scientific Projects Database; Drug Formulations; Electron Transport Complex III; Freezing; Funding; Gastric Juice; Grant; Growth; Heme; Hemeproteins; Hydrogen Peroxide; Institution; Investigation; Ions; Lead; Levodopa; Malignant Neoplasms; Melanins; Melanoma Cell; Metabolic Biotransformation; Metal Ion Binding; Metalloproteins; Metals; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Research; Research Personnel; Resources; Roentgen Rays; Role; Simulate; Solutions; Source; Structure; System; Thinking; Toxin; United States National Institutes of Health; base; cell killing; chromium hexavalent ion; diabetic; dietary supplements; lead ion; melanoma; prevent; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hard X-ray XAS studies will be conducted on metalloproteins, metal-based drugs, genotoxic species of relevance to metal-induced cancers, and other bioinorganic systems. Heme protein studies will be conducted, in which Fe K-edge investigations will be focused on the binding of small molecules to the heme, in order to understand the factors that influence whether such binding is used as a switch in a biological function, or to transport (or store) the small molecule. K-edge Cr XAS studies will be used to determine the structures of frozen solutions of reactive Cr(VI), Cr(V) and Cr(IV) species of relevance to Cr-induced cancers. Many of these species are too reactive to be crystallized and can only be generated as transients in solution. Similarly, Cr(III) complexes are used as dietary supplements and potential anti-diabetics, but the active species are poorly characterized. XAFS will be used to characterize intermediates with biomolecules that are thought to be relevant to the biotransformations of such dietary supplements. The binding of metal ions to melanin is an important way in which melanoma cells prevent metal ions from leading to cell death, because melanoma cells contain relatively high intracellular concentration of H2O2 that reacts with metal ions to lead to toxins that would kill the cells and hence prevent the growth of melanomas. Hence are investigating the binding of metals ions to melanin and their roles in forming melanin from L-dopa using K-edge XAFS. Finally, we are investigating the structures of Cu, Ni and Zn anti-inflammatory drugs in pharmaceutical preparations and artificial gastric juices in order to understand how the structure of the complexes affects their efficacy and side-effects. By understanding their stabilities and structures in different formulations and their biotransformations in simulated gastric juices, we will optimize pharmaceutical formulations and gain a better understanding of the pharmacology of these drugs.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 硬X射线XAS研究将对金属蛋白，金属药物，与金属诱导的癌症相关的遗传毒性物种以及其他生物无机系统进行。将进行血红素蛋白研究，其中Fe K边缘研究将集中在小分子与血红素的结合上，以了解影响这种结合是生物学功能中的开关还是运输（或存储）小分子的因素。 K-EDGE CR XAS研究将用于确定与CR诱导的癌症相关性的反应性CR（VI），CR（V）和CR（IV）物种的冷冻溶液的结构。这些物种中的许多太活性了，无法结晶，只能作为溶液中的瞬变产生。同样，CR（III）复合物被用作饮食补充剂和潜在的抗糖尿病药，但活性物种的特征很差。 XAFS将用于表征与被认为与此类饮食补充剂的生物转化有关的生物分子的中间体。金属离子与黑色素的结合是黑色素瘤细胞防止金属离子导致细胞死亡的一种重要方法，因为黑色素瘤细胞含有相对较高的H2O2，与金属离子反应相对较高，从而导致毒素会导致毒素杀死细胞，从而防止黑色素瘤的生长。因此，正在研究金属离子与黑色素的结合及其在使用K边缘XAFS从L-DOPA形成黑色素中的作用。最后，我们正在研究药物制剂和人造胃汁中Cu，Ni和Zn抗炎药的结构，以了解复合物的结构如何影响其功效和副作用。通过了解它们在不同配方中的稳定性和结构，及其在模拟胃汁中的生物转化，我们将优化药物制剂，并更好地了解这些药物的药理学。