Metal Coordination Compounds as Reporters for Biological NO

金属配位化合物作为生物 NO 的报告基因

• 批准号: 0907905
• 负责人: Stephen Lippard
• 金额: $ 80.1万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0907905&HistoricalAwards=false
• 关键词: Metal; Coordination; Compounds; Reporters; Biological

This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Stephen Lippard, Massachusetts Institute of Technology, to employ metal coordination complexes as reporting probes for biological nitric oxide (NO). Nitric oxide is an important molecule that controls many biological functions including smooth muscle dilation in the heart and other organs, signaling in the brain, and functioning of the immune system. This project investigates these roles through the preparation and application of bright, light-emitting molecules based on transition metal chemistry to track the generation and translocation of nitric oxide to its biological targets. Included among the targets are units in proteins that contain iron or zinc bound to sulfur, and the reactions of these units with nitric oxide and its derivatives are being investigated to provide benchmarks for interpreting the chemistry that transduces the action of NO in living systems. Graduate and postdoctoral researchers on the project are mentors to undergraduate research opportunity participants at the Massachusetts Institute of Technology. These scientists are trained to communicate their work; many subsequently assume key positions in academic or industrial organizations and some are active in outreach programs at local schools in the Cambridge and Boston communities.Sensors for nitric oxide will facilitate the screening of chemical libraries for inhibitors of the enzyme that produces NO in Gram-positive bacteria such as anthrax and Staph. aureus, thus providing leads for novel antibiotics. The chemistry of nitric oxide with iron-sulfur clusters will help guide efforts to develop catalysts for environmental cleanup since nitrogen oxides are toxic byproducts of fuel combustion processes.

无机，生物无机和有机化学计划的这项研究奖支持马萨诸塞州理工学院的Stephen Lippard教授的工作，采用金属配位络合物作为生物一氧化氮（NO）的报告探针。一氧化氮是控制许多生物功能的重要分子，包括心脏和其他器官中的平滑肌扩张，大脑中的信号传导和免疫系统的功能。该项目通过基于过渡金属化学的明亮发光分子的制备和应用来研究这些作用，以跟踪一氧化氮的产生和转移到其生物靶点。目标包括蛋白质中含有与硫结合的铁或锌的单位，这些单位与一氧化氮及其衍生物的反应正在研究中，以提供解释生命系统中转导NO作用的化学反应的基准。该项目的研究生和博士后研究人员是马萨诸塞州理工学院本科生研究机会参与者的导师。这些科学家接受过交流工作的培训;许多人后来在学术或工业组织中担任重要职务，有些人积极参与剑桥和波士顿社区当地学校的推广计划。一氧化氮传感器将有助于筛选化学库中的酶抑制剂，该酶在革兰氏阳性菌（如炭疽菌和葡萄球菌）中产生NO。金黄色葡萄球菌，从而为新的抗生素提供线索。氮氧化物与铁硫簇的化学反应将有助于指导开发环境净化催化剂的努力，因为氮氧化物是燃料燃烧过程的有毒副产品。