NOVARTIS PARTNER TIME (PRIVATE SECTOR RESEARCH)

诺华合作伙伴时间（私营部门研究）

• 批准号: 7954175
• 负责人: DIRKSEN E BUSSIERE
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954175
• 关键词: 1-Phosphatidylinositol 3-Kinase; AKT3 gene; ATP phosphohydrolase; Binding Proteins; Biological; CSF1R gene; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Data Collection; Drug Delivery Systems; Drug Design; Enzymes; Eukaryota; Funding; Goals; Grant; Heat-Shock Proteins 90; Human; Institution; Lead; Ligands; Molecular Models; PDPK1 gene; Pharmaceutical Chemistry; Phosphotransferases; Private Sector; Prokaryotic Cells; Protein Isoforms; Proteins; Receptor Protein-Tyrosine Kinases; Research; Research Personnel; Resources; Source; Structure; Synchrotrons; Therapeutic Intervention; Time; United States National Institutes of Health; X-Ray Crystallography; base; improved; molecular modeling; programs; structural biology; synchrotron radiation

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. NTP-binding proteins, such as kinases and ATPases, are important effectors of biological activity in both prokaryotes and eukaryotes. Because of this, they serve as nodes for therapeutic intervention and are thus critical drug targets. In the following experimental program we propose to perform structural studies on several key human NTP-binding proteins to further elucidate their mechanism of function as well as to integrate these proteins into an iterative structure-based drug design cycle. An iterative structure-based drug design cycle typically begins by solving the structure of the drug target by X-ray crystallography; this structure and numerous drug target:lead compound (target:ligand) co-structures are used in combination with molecular modeling and medicinal chemistry to synthesize lead compounds with improved potency and other improved characteristics. The cycle is continued until all compound optimization is completed. A rapid turn-around time is critical to the cycle and thus synchrotron data collection is of paramount importance. Our goal is to perform structural studies and iterative structure-based drug design on 7 projects: human AKT3, human CSF1R, human EG5, human HSP90, human PDK1, human PI3 kinase (both alpha and gamma isoforms), and various human receptor tyrosine kinases. The purpose of these studies will be to understand the mechanism of action of these enzymes, as well as to integrate each into a structure-based drug design cycle.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 NTP结合蛋白，如激酶和ATP酶，是原核生物和真核生物中重要的生物活性效应子。 正因为如此，它们作为治疗干预的节点，因此是关键的药物靶点。 在下面的实验计划中，我们建议对几种关键的人NTP结合蛋白进行结构研究，以进一步阐明其功能机制，并将这些蛋白整合到基于结构的迭代药物设计周期中。 迭代的基于结构的药物设计周期通常通过X射线晶体学解决药物靶标的结构开始;该结构和许多药物靶标：先导化合物（靶标：配体）共结构与分子建模和药物化学结合使用，以合成具有改善的效力和其他改善的特性的先导化合物。 继续该循环，直到完成所有化合物优化。 一个快速的周转时间是至关重要的周期，因此同步数据收集是至关重要的。 我们的目标是在7个项目上进行结构研究和迭代的基于结构的药物设计：人AKT 3，人CSF 1 R，人EG 5，人HSP 90，人PDK 1，人PI 3激酶（α和γ亚型）和各种人受体酪氨酸激酶。 这些研究的目的是了解这些酶的作用机制，并将其整合到基于结构的药物设计周期中。