Mechanism and Inhibition of Histone Modifications
组蛋白修饰的机制和抑制
基本信息
- 批准号:10621492
- 负责人:
- 金额:$ 37.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylationArginineBiologicalBiological ProcessBiologyCell physiologyChemicalsCoupledDevelopmentDiabetes MellitusDiseaseDisease PathwayEnzymesEpigenetic ProcessGenetic TranscriptionGoalsInfectionInflammationInvestmentsLaboratory ResearchLysineMalignant NeoplasmsMediatingMetabolic PathwayMetabolismMethodsMethylationMethyltransferaseMolecularMolecular TargetMutateOrganismPathogenesisPathologyPathway interactionsPharmaceutical PreparationsPhysiologyPost-Translational Protein ProcessingProcessProtein IsoformsProtein MethylationProtein MethyltransferasesProtein-Arginine N-MethyltransferaseRNA SplicingRegulationResearchSignal TransductionStructureTranslatingTranslationsdesigndrug discoveryexperimental studyhistone modificationhuman diseaseinnovationmembernervous system disordernovelnovel therapeuticsoverexpressionpathogenprogramsprotein functiontargeted treatmenttherapeutic candidatetherapy developmenttool
项目摘要
Protein methylation on arginine and lysine residues represents a type of versatile posttranslational modifications
occurring in all eukaryotic organisms. Protein methyltransferases regulate a plethora of cellular processes
ranged from gene transcription, RNA splicing, translation, metabolic pathways, to signal transduction. Many
protein methyltransferases are found to be overexpressed or mutated in common human diseases such as
cancer, inflammation, diabetes, neurological disorders, and infection. Hence, protein methyltransferases are
highly promising novel molecular targets in drug discovery. However, biological functions of the majority of
protein methyltransferase enzymes in dictating normal physiology and disease pathways are only poorly defined.
Our long-term research goal is to elucidate biological pathways whereby key protein methyltransferases
contribute to the pathogenesis of recalcitrant diseases such as cancer and infection, and meanwhile to discover
new structural chemotypes for protein methyltransferase-targeted therapy. The present research program is
aimed at investigating molecular mechanisms and functions of protein methylation catalyzed by key
methyltransferases. Our effort is coupled with and aided by development and application of innovative chemical
biology methods and tools. Built upon our recent preliminary results, we will implement experiments to elucidate
novel molecular mechanisms and regulation of protein arginine methyltransferase (PRMT) activities. We will
extend our efforts to investigate the activity, structure and function of untapped protein methyltransferases,
including those in different organisms such as infectious pathogens. Particular efforts will be directed to develop
isoform-selective modulators and probes for important PRMT members and apply them to elucidate PRMT-
regulated cellular pathways and disease processes. Further efforts will be invested to interrogate potential cross-
interactions of protein methylation with lysine acetylation in orchestrating biological regulation. The results of the
proposed research together will yield an in-depth understanding of the regulatory mechanism and biological
significance of protein methylation in the control of normal physiology and disease pathology, and translate
laboratory research leads into therapeutic candidates for the treatment of protein methyltransferase-controlled
ailments.
精氨酸和赖氨酸残基上的蛋白质甲基化是一种多功能的翻译后修饰
存在于所有真核生物中的。蛋白质甲基转移酶调节过多的细胞过程
从基因转录、RNA剪接、翻译、代谢途径到信号转导。许多
蛋白质甲基转移酶在常见的人类疾病中被发现过度表达或突变,例如
癌症、炎症、糖尿病、神经疾病和感染。因此,蛋白质甲基转移酶是
在药物发现中极具前景的新分子靶点。然而,大多数细胞的生物学功能
蛋白质甲基转移酶在决定正常生理和疾病途径中的作用还不是很清楚。
我们的长期研究目标是阐明关键蛋白甲基转移酶
有助于癌症和感染等顽固性疾病的发病机制,同时发现
蛋白质甲基转移酶靶向治疗的新结构化学类型。目前的研究计划是
旨在研究KEY催化蛋白质甲基化的分子机制和功能
甲基转移酶。我们的努力是与创新化学品的开发和应用相结合并得到帮助的
生物学方法和工具。在我们最近的初步结果的基础上,我们将进行实验来阐明
蛋白质精氨酸甲基转移酶(PRMT)活性的新分子机制和调控。我们会
继续努力研究未开发的蛋白质甲基转移酶的活性、结构和功能,
包括不同生物体中的那些,如传染性病原体。将作出特别努力,以发展
重要PRMT成员的异构体选择性调节剂和探针,并应用于阐明PRMT-
受调控的细胞通路和疾病过程。将投入进一步的努力来审问潜在的交叉
蛋白质甲基化与赖氨酸乙酰化在协调生物调节中的相互作用。评选结果
拟议的研究将产生对调节机制和生物学的深入理解。
蛋白质甲基化在控制正常生理和疾病病理中的意义及其翻译
实验室研究引导出治疗蛋白质甲基转移酶控制的候选药物
病痛。
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)
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{{ truncateString('Y. George Zheng', 18)}}的其他基金
Develop Potent Methyltransferase Inhibitors to Target Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
开发有效的甲基转移酶抑制剂来治疗严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2)
- 批准号:
10175592 - 财政年份:2021
- 资助金额:
$ 37.3万 - 项目类别:
Mechanism and Inhibition of Protein Arginine Methylation
蛋白质精氨酸甲基化的机制及抑制
- 批准号:
10079491 - 财政年份:2018
- 资助金额:
$ 37.3万 - 项目类别:
Mechanism and Inhibition of Protein Arginine Methylation
蛋白质精氨酸甲基化的机制及抑制
- 批准号:
10392637 - 财政年份:2018
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
8528619 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
7986077 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
8324722 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
8136011 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
8725683 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Chemical Approaches to Protein Arginine Methylation
蛋白质精氨酸甲基化的化学方法
- 批准号:
8693069 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
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