PROJECT 1- CHEMICAL BIOLOGY OF ARISTOLOCHIC ACIDS

项目 1-马兜铃酸的化学生物学

• 批准号: 7651412
• 负责人: FRANCIS JOHNSON
• 金额: $ 39.12万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7651412
• 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

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，采用的合成路线通常是 适用于掺入源自亚里士醇胆道-L（AA-1）和其他AA的加合物的DNA中 类似物。 该小组还评论说，进度报告没有解决以前的目标... 能够采用成功的一致方法的能力。提出了原始建议的目标2和3 如进度报告中所述，积极的是，但并未导致出版物。在AIM 2的情况下 词汇素的选择性不能在寡聚DNA的水平上再现。 AIM 3的前提； Bisphenol A的氧化产物无法确认其诱变行为。 因此，我们转向一个与该PPG研究的长期目标直接相关的项目，并在 开发一种新的方法来引入苯甲甲酸二醇加合物