EXPLORING AND DEFINING THE ROLE OF LIGAND OXIDATION IN RU(II) ARENE-BASED DRUGS
探索和定义配体氧化在 RU(II) 芳烃类药物中的作用
基本信息
- 批准号:8362167
- 负责人:
- 金额:$ 0.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2012-02-29
- 项目状态:已结题
- 来源:
- 关键词:Antineoplastic AgentsBiochemicalBiologicalCharacteristicsComplexDrug Delivery SystemsEnvironmentFundingGrantLigandsNational Center for Research ResourcesNaturePharmaceutical PreparationsPharmacologic SubstancePrincipal InvestigatorPropertyRadiationResearchResearch InfrastructureResourcesRoleRutheniumSeleniumSeriesSourceUnited States National Institutes of Healthanalogbasecostdrug candidatemetal complexoxidationstructural biology
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
Defining and understanding the mechanisms of action of pharmaceutical agents is an ongoing research challenge that requires detailed information on the reactivity of these drugs within a biological environment. The challenge is generally more complex for metal-based drug candidates due to their broader reactivity and the correspondingly greater possibilities for interactions during transport to the biological target. We are investigating the fundamental biochemical properties of a series of ruthenium-based drug targets with demonstrated antitumor activity. Ru arene complexes of the form [Ru(ar)(en)L]X have shown excellent activity as anticancer agents but the nature of L has an important, yet somewhat unpredictable effect on bioactivity. We note particularly that thiolato complexes (L=RS-) are extremely bioactive under acidic and oxidative conditions. The properties of different oxidized forms of these complexes (e.g. L=RSO-, RSOH, RSO2-, RSO2H) and their related selenium analogs are currently being explored and show unusual bonding characteristics that are believed to be very relevant to their bioactivity. We therefore propose to utilize S K-edge and Se K-edge XAS (as well as other ligand K-edges where appropriate) to evaluate the nature of Ru-X bonding in these and related species.
该子项目是利用资源的众多研究子项目之一
由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持
并且子项目的主要研究者可能是由其他来源提供的,
包括其他 NIH 来源。 子项目可能列出的总成本
代表子项目使用的中心基础设施的估计数量,
NCRR 赠款不直接向子项目或子项目工作人员提供资金。
定义和理解药剂的作用机制是一项持续的研究挑战,需要有关这些药物在生物环境中的反应性的详细信息。对于金属候选药物来说,挑战通常更加复杂,因为它们具有更广泛的反应性,并且相应地在运输到生物靶标期间发生相互作用的可能性也更大。我们正在研究一系列具有抗肿瘤活性的钌基药物靶点的基本生化特性。 [Ru(ar)(en)L]X 形式的 Ru 芳烃配合物作为抗癌剂表现出优异的活性,但 L 的性质对生物活性具有重要但有些不可预测的影响。我们特别注意到硫醇络合物 (L=RS-) 在酸性和氧化条件下具有极高的生物活性。目前正在探索这些复合物的不同氧化形式(例如L=RSO-、RSOH、RSO2-、RSO2H)及其相关的硒类似物的特性,并显示出不寻常的键合特性,这些特性被认为与其生物活性非常相关。因此,我们建议利用 S K-edge 和 Se K-edge XAS(以及其他适当的配体 K-edge)来评估这些和相关物种中 Ru-X 键合的性质。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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PIERRE KENNEPOHL的其他文献
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{{ truncateString('PIERRE KENNEPOHL', 18)}}的其他基金
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
8362127 - 财政年份:2011
- 资助金额:
$ 0.33万 - 项目类别:
EXPLORING AND DEFINING THE ROLE OF LIGAND OXIDATION IN RU(II) ARENE-BASED DRUGS
探索和定义配体氧化在 RU(II) 芳烃类药物中的作用
- 批准号:
8170118 - 财政年份:2010
- 资助金额:
$ 0.33万 - 项目类别:
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
8170054 - 财政年份:2010
- 资助金额:
$ 0.33万 - 项目类别:
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
7954378 - 财政年份:2009
- 资助金额:
$ 0.33万 - 项目类别:
EXPLORING AND DEFINING THE ROLE OF LIGAND OXIDATION IN RU(II) ARENE-BASED DRUGS
探索和定义配体氧化在 RU(II) 芳烃类药物中的作用
- 批准号:
7954448 - 财政年份:2009
- 资助金额:
$ 0.33万 - 项目类别:
STRUCTURE AND REDOX CHEMISTRY OF TRUNCATED AMYLOID AGGREGATES
截短的淀粉样蛋白聚集体的结构和氧化还原化学
- 批准号:
7954473 - 财政年份:2009
- 资助金额:
$ 0.33万 - 项目类别:
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
7722039 - 财政年份:2008
- 资助金额:
$ 0.33万 - 项目类别:
EXPLORING AND DEFINING THE ROLE OF LIGAND OXIDATION IN RU(II) ARENE-BASED DRUGS
探索和定义配体氧化在 RU(II) 芳烃类药物中的作用
- 批准号:
7722144 - 财政年份:2008
- 资助金额:
$ 0.33万 - 项目类别:
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
7721804 - 财政年份:2008
- 资助金额:
$ 0.33万 - 项目类别:
XAS AS A NOVEL PROBE OF ELECTRONIC STRUCTURE AND REACTIVITY FOR PROTEIN-BASED SU
XAS 作为蛋白质 SU 电子结构和反应性的新型探针
- 批准号:
7598007 - 财政年份:2007
- 资助金额:
$ 0.33万 - 项目类别:
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