Rational design and molecular characterisation of novel bacterial RNA polymerase inhibitors

新型细菌RNA聚合酶抑制剂的合理设计和分子表征

• 批准号: G0600810/1
• 负责人: Ian Chopra
• 金额: $ 89.69万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600810%2F1
• 关键词: Rational; design; molecular; characterisation; novel

Bacterial infections are a major cause of human disease. Until recently most infections were easily treated with a range of antibiotics discovered and developed during the golden age of antibiotic discovery between 1940 and 1970. However, there has now been a dramatic rise in the incidence of bacterial resistance to existing antibiotics, leading to the possibility of returning to a pre-antibiotic era when only palliative care could be administered. A disturbing feature has been the emergence of bacteria multiply resistant to antibiotics, the so-called superbugs. Two very important examples of such bacteria are methicillin-resistant S.aureus (MRSA) and multiple drug resistant tuberculosis (MDR TB). New antibiotics are urgently required to combat these bacteria. The identification and characterisation of new inhibitors of RNAP, an essential bacterial enzyme, as proposed in this grant application, will provide new approaches to relieve the burden of disease caused by infectious drug resistant bacteria, . The newly identified inhibitors, or molecules subsequently derived from first-generation inhibitors, could become candidates for development as antibiotics. Ultimately it is hoped that new antibiotics, identified by the proposed research, will be used to treat life-threatening bacterial infections in man such as MRSA and TB. We anticipate that this will include patients suffering from these infections in the United Kingdom.

细菌感染是人类疾病的主要原因。直到最近，大多数感染都可以很容易地用1940年至1970年抗生素发现黄金时期发现和开发的一系列抗生素来治疗。然而，现在细菌对现有抗生素的抗药性急剧上升，导致有可能回到抗生素出现之前的时代，那时只能进行姑息治疗。一个令人不安的特征是出现了对抗生素产生繁殖抗药性的细菌，即所谓的超级细菌。这类细菌的两个非常重要的例子是耐甲氧西林金黄色葡萄球菌(MRSA)和耐多药结核病(MDR TB)。迫切需要新的抗生素来对抗这些细菌。RNAP是一种基本的细菌酶，如本赠款申请中所建议的那样，其新的抑制剂的鉴定和表征将为减轻传染性耐药细菌造成的疾病负担提供新的方法。新发现的抑制剂，或后来从第一代抑制剂衍生出来的分子，可能成为开发抗生素的候选药物。最终，人们希望这项拟议的研究确定的新抗生素将用于治疗威胁人类生命的细菌感染，如MRSA和结核病。我们预计，这将包括在英国遭受这些感染的患者。