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PROJECT 1- CHEMICAL BIOLOGY OF ARISTOLOCHIC ACIDS

项目 1-马兜铃酸的化学生物学

基本信息

批准号：
7305791
负责人：
FRANCIS JOHNSON
金额：
$ 38.81万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7305791
关键词：
Address Animals Aristolochic Acids Behavior Biological Biology Carboxylic Acids Carcinogens Cells Chemicals Chronic DNA DNA Adducts Development End stage renal failure Event Goals Hot Spot Human Impairment Induced Mutation Kidney Diseases Life Malignant Neoplasms Metabolic Activation Methods NMR Spectroscopy Nephrotoxic Nucleotide Excision Repair Oligonucleotides Program Research Project Grants Progress Reports Publications Published Comment Renal Tissue Renal function Research Research Personnel Research Project Grants Resolution Role Route Series Shuttle Vectors Site Solutions Specificity Structure Structure-Activity Relationship System Thermodynamics Toxic effect adduct analog aristolochic acid I bisphenol A chemical synthesis ds-DNA lexitropsin molecular dynamics novel oxidation phosphoramidite programs protein structure repaired three dimensional structure

项目摘要

in the Progress Report. Importantly, the synthetic route employed is generally applicable to the incorporation into DNA of adducts derived from aristolochic acid-l (AA-1) and other AA analogs. The Panel also commented that the progress report does not address previous aims ... there is concern about the ability to mount a successful concerted approach. Aims 2 and 3 of the orginal proposal were pursued actively, as described in the Progress Report, but did not result in publications. In the case of Aim 2, the selectivity of the lexitropsins could not be reproduced at the level of oligomeric DNA. The premise of Aim 3; that oxidation products of bisphenol A are responsible for their mutagenic behaviour, could not be confirmed. We therefore turned to an project directly related to the long-term goals of this PPG research and, in developing a novel method for introducing benzpyrenediolepoxide adducts

在进度报告中。重要的是，所采用的合成路线通常是适用于马兜铃酸-I（AA-1）和其它AA衍生的加合物掺入DNA 类似物专家小组还评论说，进度报告没有涉及以前的目标.。人们担心有能力采取成功的协调一致的办法。原提案的目标2和3得到了实现如进度报告所述，这些活动积极开展，但没有产生出版物。就目标2而言， lexitropsin的选择性不能在寡聚DNA水平上重现。目标3的前提; 双酚A的氧化产物是其致突变行为的原因，这一点无法得到证实。因此，我们转向了一个与PPG研究的长期目标直接相关的项目，开发一种引入苯并芘二醇环氧加合物的新方法