FLUORESCENT CARCINOGEN-LIKE BRIDGED ANNULENES

荧光类致癌物桥环烯

• 批准号: 3841352
• 负责人: EARL DOOMES
• 金额: --
• 依托单位: SOUTHERN UNIV A&M COL BATON ROUGE
• 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/3841352
• 关键词: DNA; alkylating agents; antineoplastics; benzanthracenes; benzopyrenes; bridged cyclic compound; busulfan; charge transfer complex; chemical carcinogen; chemical group; chemical reaction; chemical structure function; chemical synthesis; chromatin; crosslink; diene; drug design /synthesis /production; fluorescence spectrometry; fluorescent dye /probe; histones; nuclear magnetic resonance spectroscopy; nucleic acid structure; protein structure; stereochemistry

The long range objectives of the proposed research may be divided into two general categories. In the first phase, we plan to develop methods of synthesis and study mechanisms of reactions of 2-aroyl- and 2-arenesulfonyl allyl amines. Chemical data on these activated allylamino substrates will be utilized in the overall evaluation of these agents as potential anti-tumor agents. Additionally, bis-allylamino sulfonyl arenas and bis-allylamino aroyl substrates will be characterized. These polyfunctional alkylating agents are being examined as analogs of quinone methides, an important class of biologically active organic compounds. The 2-arenesulfonyl- and 2-aroylallylamino substrates represent a new class of alkylating agents that will be developed as general fluorescent probes for proteins and nucleic acids. We plan to examine in detail the reactivities of 2-(naphthalenesulfonly)2-(naphthoyl)- and 2-(phenanthroyl)-allylamino substrates toward oligopeptides, histones and nucleic acids. Derivatives of activated allylamino substrates containing two functional groups on the arene substituent will be synthesized. The second section of the research objectives deals with transformations of cyclophane dienes to carcinogen-like bridged annulenes and to rigid polyfunctional alkylating agents. We shall concentrate our efforts on the synthesis of (1, 5, 10) methano [41] annulene, its benzo derivative, and polyfunctional allylamino substances derived from it. Bis-sulfonate esters and bis-allylamino substrates derived from [9] metacyclophane diene will be synthesized and investigated in terms of their effect on physical properties of deoxyribonucleic acid (DNA). Another important objective of this component of the MBRS program is to introduce undergraduate and graduate students to basic and modern techniques of biochemical and chemical research.

拟议研究的远程目标可以分为 两个一般类别。在第一阶段，我们计划开发方法 2-弧度和研究机制的合成和研究机制 2-芳烃烯丙基胺。这些激活的Allylamino的化学数据 底物将用于对这些代理的总体评估 潜在的抗肿瘤剂。此外，bis-亚利氨基磺胺sulfonyl竞技场 和Bis-Alllamino Aroyl底物将被描述。这些 多功能烷基化剂正在研究为喹酮的类似物 甲基，一类重要的具有生物活性的有机化合物。 2-芳烃和2-芳岛酰氨基氨基底物代表了一个新的 将作为一般荧光开发的烷基化剂类 蛋白质和核酸的探针。我们计划详细检查 2-（萘甲磺基）2-（萘）的反应率 - 2-（苯甜基） - 乙酰基氨基底物朝向寡肽，组蛋白和 核酸。活性烯丙基氨基底物的衍生物 将合成Arene取代基上的两个官能团。这 研究目标的第二部分涉及 环泳二烯对癌变的桥接环和刚性 多功能烷基化剂。我们将集中精力 （1，5，10）Methano [41] Annulene的合成，其苯并衍生物和 从中得出的多功能烯丙基氨基物质。二硫酸盐 酯和Bis- allylamino底物，源自[9] Diene将根据其对 脱氧核糖核酸（DNA）的物理特性。 MBRS计划的该组成部分的另一个重要目标是 向本科生和研究生介绍基础和现代 生化和化学研究技术。