A chemical proteomic strategy to identify novel drug targets in Plasmodium falciparum and corresponding lead compounds for the development of new antimalarials
一种化学蛋白质组学策略,用于识别恶性疟原虫中的新药物靶标和相应的先导化合物,用于开发新型抗疟药
基本信息
- 批准号:192524457
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2011
- 资助国家:德国
- 起止时间:2010-12-31 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Malaria remains one of the leading causes of morbidity and mortality in the world resulting in over a million deaths every year. In view of the widespread development of drug resistance in the parasite against commonly used drugs, there is a necessity to identify new drug targets and develop new pharmacaphores. In the present joint proposal we will utilize a novel chemical proteomic strategy termed activity based protein profiling (ABPP) to identify new targets in P. falciparum that are either essential for survival, growth or pathogenesis together with their corresponding inhibitors that can be developed as anti-malarial. We will screen small focused libraries of drug like natural product inspired compounds that inhibit the parasite growth and then utilize ABPP as chemical-proteomic approach to identify and the corresponding essential drug targets in P. falciparum. Selected biologically relevant targets identified by these analyses will be cloned and recombinant proteins will be expressed. As preliminary work we have already identified some β-lactone compounds that inhibit parasite growth and also identified their potential protease targets in the parasite. Detailed in vitro interaction studies and enzyme activity inhibition studies will be carried out using the recombinant proteins and targeting compounds. Derivatives of these compounds will be designed to identify molecules of higher affinity binding/activity inhibition and higher efficacy to inhibit parasite growth. Selected compounds will be further assessed for their ability to inhibit growth of parasites in a mouse-malaria model.
疟疾仍然是世界上发病率和死亡率的主要原因之一,每年造成100多万人死亡。鉴于寄生虫对常用药物的耐药性的广泛发展,有必要确定新的药物靶点并开发新的药效团。在本联合提案中,我们将利用一种新的化学蛋白质组学策略,称为基于活性的蛋白质谱(ABPP),以确定恶性疟原虫中对生存,生长或发病机制至关重要的新靶标,以及可以开发为抗疟疾的相应抑制剂。我们将筛选小型集中的药物库,如抑制寄生虫生长的天然产物激发的化合物,然后利用ABPP作为化学蛋白质组学方法来识别恶性疟原虫中相应的必需药物靶标。将克隆通过这些分析鉴定的选定生物学相关靶标,并表达重组蛋白。作为初步工作,我们已经鉴定了一些抑制寄生虫生长的β-内酯化合物,并鉴定了它们在寄生虫中的潜在蛋白酶靶标。将使用重组蛋白和靶向化合物进行详细的体外相互作用研究和酶活性抑制研究。将设计这些化合物的衍生物以鉴定具有更高亲和力结合/活性抑制和更高抑制寄生虫生长效力的分子。将进一步评估所选化合物在小鼠疟疾模型中抑制寄生虫生长的能力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Professor Dr. Stephan A. Sieber其他文献
Professor Dr. Stephan A. Sieber的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Professor Dr. Stephan A. Sieber', 18)}}的其他基金
Exploiting quorum sensing inhibition of the natural products fimbrolide and elegaphenone in gram-negative bacteria
利用群体感应抑制革兰氏阴性菌中的天然产物芬溴内酯和榄香酮
- 批准号:
358921956 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Chemical-proteomic tools to monitor pyridoxal phosphorylation and its function as an enzyme cofactor in disease-related pathways
用于监测吡哆醛磷酸化及其作为疾病相关途径中酶辅因子的功能的化学蛋白质组学工具
- 批准号:
314976069 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Identification of chemical compounds to inhibit the caseinolytic protease ClpXP complex and evaluate their biological activity
抑制酪蛋白分解酶 ClpXP 复合物的化合物的鉴定并评估其生物活性
- 批准号:
282324388 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Research Grants
Protein targets of rugulactone and illudin S: An analysis of their function and mechanism of action
胡古内酯和隐球菌素 S 的蛋白质靶点:功能和作用机制分析
- 批准号:
233925483 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Identification, validation and functional characterization of targets of myxobacterial compounds with potential for pharmacological cancer treatment
具有药物癌症治疗潜力的粘细菌化合物靶标的鉴定、验证和功能表征
- 批准号:
187769183 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Research Units
Chemisch-proteomische Strategien zur Identifikation krankheitsassoziierter Enzyme in pathogenen Bakterien als neuartige Angriffsziele für Antibiotika
化学蛋白质组学策略识别病原菌中与疾病相关的酶作为抗生素的新靶标
- 批准号:
28198381 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Independent Junior Research Groups
A Proteomic Strategy for Inhibiting Cancer-Associated Enzymes
抑制癌症相关酶的蛋白质组学策略
- 批准号:
5438978 - 财政年份:2004
- 资助金额:
-- - 项目类别:
Emmy Noether International Fellowships
Deciphering the structure activity relationship, mode of action and uptake of isonitrile antibiotics in Gram-negative bacteria
破译革兰氏阴性菌中异腈抗生素的结构活性关系、作用方式和摄取
- 批准号:
505074737 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
相似海外基金
Identification of sub-phenotypes of severely ill burn patients and risk for secondary sepsis: SEPSISBURN
识别严重烧伤患者的亚表型和继发性败血症的风险:SEPSISBURN
- 批准号:
10720049 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Proteomic Analysis of Implant Surfaces in Athroplasty Failure
关节置换术失败中植入物表面的蛋白质组学分析
- 批准号:
10623873 - 财政年份:2023
- 资助金额:
-- - 项目类别:
A Single Cell and Proteomic Precision Medicine Approach to Glyburide Responsive Contusion Expansion in Severe Traumatic Brain Injury
单细胞和蛋白质组精准医学方法治疗严重创伤性脑损伤中的格列本脲反应性挫伤扩张
- 批准号:
10645458 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Proteomic and epigenetic alterations associated with plant-based diets and CVD
与植物性饮食和心血管疾病相关的蛋白质组学和表观遗传改变
- 批准号:
10900009 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Proteomic and epigenetic alterations associated with plant-based diets and CVD
与植物性饮食和心血管疾病相关的蛋白质组学和表观遗传改变
- 批准号:
10643149 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Integrating Polygenic Risk and Environmental Exposures to Uncover Biological Mechanisms Underlying Dementia in a Diverse Cohort
整合多基因风险和环境暴露来揭示不同人群中痴呆症的生物机制
- 批准号:
10560160 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Research Project 1 PDAC Molecular Subtypes Contribute to Cancer Health Disparities
研究项目 1 PDAC 分子亚型导致癌症健康差异
- 批准号:
10733314 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Proteomic and integrative omic profiles of sugar- and artificially sweetened beverage consumption and changes in type 2 diabetes risk factors
糖和人工甜味剂饮料消费的蛋白质组学和综合组学特征以及 2 型糖尿病危险因素的变化
- 批准号:
10723200 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Multi-omic dissection of clonal hematopoiesis-associated diseases
克隆造血相关疾病的多组学解剖
- 批准号:
10644764 - 财政年份:2023
- 资助金额:
-- - 项目类别:
ADDRESSING THE CONTINUING CHALLENGE OF IDENTIFYING AND MANAGING CORONARY RISK: A PERSON-SPECIFIC STRATEGY USING PROTEOMICS
应对识别和管理冠状动脉风险的持续挑战:利用蛋白质组学的个体化策略
- 批准号:
10549983 - 财政年份:2022
- 资助金额:
-- - 项目类别: