Purine Analog Anti-Mycobacterial Drug Development
嘌呤类似物抗分枝杆菌药物开发
基本信息
- 批准号:7232669
- 负责人:
- 金额:$ 46.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-01-01 至 2010-03-31
- 项目状态:已结题
- 来源:
- 关键词:2-methyladenosineAdenosineAdenosine KinaseAntimycobacterial AgentsAntitubercular AgentsAntiviral AgentsApplications GrantsBiochemicalBiochemical GeneticsBiochemical PharmacologyBiochemistryBiologicalCellsCharacteristicsChemistryClinicalComplementContractsCrystallizationDataDevelopmentDoctor of PhilosophyDrug DesignEnzymesEvaluationFundingGenerationsGenesGenus MycobacteriumGoalsGovernmentGrantGuanosineHomologous GeneHumanKnowledgeLeadLearningLibrariesMetabolicMetabolismMethodologyMethodsMycobacterium tuberculosisNew AgentsNucleosidesPathway interactionsPharmaceutical ChemistryPharmaceutical PreparationsPhasePhosphotransferasesPropertyPurine NucleosidesPurinesRecombinantsRecording of previous eventsResearch InstituteResourcesRoentgen RaysScientistScreening procedureSolidStructureStructure-Activity RelationshipSystemToxic effectTuberculosisViral CancerVirus Diseasesanalogantimicrobialbasecofactorcytotoxicitydesigndrug developmentenzyme mechanismenzyme pathwayevaluation/testingexpression cloningguanosine kinasehuman diseaseimprovedinhibitor/antagonistinsightiterative designkillingsmacrophagemetabolic abnormality assessmentmutantmycobacterialnovelnucleoside analogprogramspurinepurine analogpurine metabolism
项目摘要
DESCRIPTION (provided by applicant):
Through the NIAID-sponsored Tuberculosis Anti-microbial Acquisition and Coordinating Facility (TAACF), we have identified numerous anti-Mycobacterium tuberculosis lead compounds, which are structurally similar to purine bases and nucleosides. In the current grant period (1999 to 2003) we have (1) synthesized many new compounds and evaluated them for activity against M. tb, (2) characterized the biochemical pharmacology of one of the lead compounds (2-methyladenosine), and (3) begun the characterization of the enzymes involved in purine salvage in M. tb. In the new grant proposal we plan to continue these studies to further our understanding of the enzymes involved in the purine salvage pathway in M. tb and to design and synthesize new agents with selective activity against M. tb. Much is known about the substrate requirements of human enzymes involved in purine salvage, because of the considerable effort to develop nucleoside analogs for the treatment of cancer and viral diseases. However, very little is currently known about the substrate characteristics of these enzymes in M. tb. We have identified 3 purine salvage enzymes that are expressed in M. tb that could be exploited in the development of new selective anti-/W. tb agents. Two of these enzymes (adenosine cleavage and guanosine kinase) are not expressed in human cells and we have recently shown that the third enzyme (adenosine kinase) has unique characteristics that could also be used for selective activation of nucleoside analogs. The biochemical and genetic characterization of these enzymes should provide valuable information that will be useful in the rational design and development of new agents based on metabolic differences in purine metabolism between humans and M. tb.
The proposed specific aims to accomplish the goals of this grant proposal are: (1) identification, cloning, expression, and purification of M. tb adenosine cleavage and guanosine kinase activities; (2) biochemical characterization of M. tb adenosine kinase, adenosine cleavage, and guanosine kinase activities; (3) metabolic studies with new agents that have potent and selective anti-M. tb activity; and (4) design and synthesis of purine and purine nucleoside analogs with selective activity against M. tb.
描述(由申请人提供):
通过NIAID赞助的结核病抗微生物收购和协调机构(TAACF),我们已经确定了许多抗结核分枝杆菌的先导化合物,它们在结构上与嘌呤碱基和核苷相似。在目前的资助期(1999年至2003年),我们(1)合成了许多新的化合物,并评估了它们对M。tb,(2)表征了一种先导化合物(2-甲基腺苷)的生化药理学,(3)开始表征M. TB.在新的拨款申请中,我们计划继续这些研究,以进一步了解参与M. tb的选择性抑制剂,并设计合成具有选择性抑制M. TB.由于开发用于治疗癌症和病毒性疾病的核苷类似物的相当大的努力,关于嘌呤补救中涉及的人类酶的底物需求已经知道很多。然而,目前对M. TB.我们已经鉴定了3种在M. tb,可用于开发新的选择性抗-/W。结核病代理商。其中两种酶(腺苷裂解酶和鸟苷激酶)在人类细胞中不表达,我们最近发现第三种酶(腺苷激酶)具有独特的特性,也可用于选择性激活核苷类似物。这些酶的生物化学和遗传学特性应提供有价值的信息,这将是有用的,在合理的设计和开发新的代理人之间的嘌呤代谢的代谢差异的基础上,人类和M。TB.
为实现本项目的资助目标,我们提出的具体目标是:(1)M. tb腺苷切割和鸟苷激酶活性;(2)M. tb腺苷激酶、腺苷裂解和鸟苷激酶活性;(3)具有强效和选择性抗M. tb活性;和(4)具有抗结核杆菌选择性活性的嘌呤和嘌呤核苷类似物的设计和合成。TB.
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 }}
WILLIAM B PARKER其他文献
WILLIAM B PARKER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('WILLIAM B PARKER', 18)}}的其他基金
2013 Nucleosides, Nucleotides, and Oligonucleotides Gordon Research Conference
2013年核苷、核苷酸和寡核苷酸戈登研究会议
- 批准号:
8519771 - 财政年份:2013
- 资助金额:
$ 46.37万 - 项目类别:
2011 Nucleosides, Nucleotides, and Oligonucleotides GRC
2011 核苷、核苷酸和寡核苷酸 GRC
- 批准号:
8116777 - 财政年份:2011
- 资助金额:
$ 46.37万 - 项目类别:
PURINE ANALOG ANTIMYCOBACTERIAL DRUG DEVELOPMENT
嘌呤类似物抗真菌药物的开发
- 批准号:
2797353 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
BIOCHEMISTRY OF PURINE NUCLEOSIDE ANALOGS ACTIVATED BY E COLI PNP
大肠杆菌 PNP 激活的嘌呤核苷类似物的生物化学
- 批准号:
6203306 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
Purine Analog Anti-Mycobacterial Drug Development
嘌呤类似物抗分枝杆菌药物开发
- 批准号:
7609201 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
Purine Analog Anti-Mycobacterial Drug Development
嘌呤类似物抗分枝杆菌药物开发
- 批准号:
7012750 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
PURINE ANALOG ANTIMYCOBACTERIAL DRUG DEVELOPMENT
嘌呤类似物抗真菌药物的开发
- 批准号:
6341712 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
Purine Analog Anti-Mycobacterial Drug Development
嘌呤类似物抗分枝杆菌药物开发
- 批准号:
6947999 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
Purine Analog Anti-Mycobacterial Drug Development
嘌呤类似物抗分枝杆菌药物开发
- 批准号:
7410131 - 财政年份:1999
- 资助金额:
$ 46.37万 - 项目类别:
相似国自然基金
基于ADK/Adenosine调控DNA甲基化探讨“利湿化瘀通络”法对2型糖尿病肾病足细胞裂孔膜损伤的干预机制研究
- 批准号:82074359
- 批准年份:2020
- 资助金额:55 万元
- 项目类别:面上项目
细胞外腺苷(Adenosine)作为干细胞旁分泌因子的生物学鉴定和功能分析
- 批准号:81570244
- 批准年份:2015
- 资助金额:57.0 万元
- 项目类别:面上项目
Adenosine诱导A1/A2AR稳态失衡启动慢性低灌注白质炎性损伤及其机制
- 批准号:81171113
- 批准年份:2011
- 资助金额:55.0 万元
- 项目类别:面上项目
相似海外基金
The Role of Adenosine Kinase in Mixed Diastolic Heart Failure and Alzheimer Disease
腺苷激酶在混合性舒张性心力衰竭和阿尔茨海默病中的作用
- 批准号:
10679989 - 财政年份:2023
- 资助金额:
$ 46.37万 - 项目类别:
Postnatal development of adenosine kinase in the brainstem network that controls breathing
控制呼吸的脑干网络中腺苷激酶的出生后发育
- 批准号:
573323-2022 - 财政年份:2022
- 资助金额:
$ 46.37万 - 项目类别:
University Undergraduate Student Research Awards
Adenosine kinase antisense gene therapy for temporal lobe epilepsy.
腺苷激酶反义基因治疗颞叶癫痫。
- 批准号:
9011551 - 财政年份:2015
- 资助金额:
$ 46.37万 - 项目类别:
The Role of Adenosine Kinase in Controlling Beta-Cell Regeneration
腺苷激酶在控制 β 细胞再生中的作用
- 批准号:
8888112 - 财政年份:2015
- 资助金额:
$ 46.37万 - 项目类别:
Interrogating the Role of Adenosine Kinase in Islet Beta-Cells
探讨腺苷激酶在胰岛β细胞中的作用
- 批准号:
8480250 - 财政年份:2013
- 资助金额:
$ 46.37万 - 项目类别:
Interrogating the Role of Adenosine Kinase in Islet Beta-Cells
探讨腺苷激酶在胰岛β细胞中的作用
- 批准号:
8643226 - 财政年份:2013
- 资助金额:
$ 46.37万 - 项目类别:
The role of adenosine kinase in atherosclerosis
腺苷激酶在动脉粥样硬化中的作用
- 批准号:
8583339 - 财政年份:2011
- 资助金额:
$ 46.37万 - 项目类别:
The role of adenosine kinase in atherosclerosis
腺苷激酶在动脉粥样硬化中的作用
- 批准号:
8415996 - 财政年份:2011
- 资助金额:
$ 46.37万 - 项目类别:
The role of adenosine kinase in atherosclerosis
腺苷激酶在动脉粥样硬化中的作用
- 批准号:
8764729 - 财政年份:2011
- 资助金额:
$ 46.37万 - 项目类别:
The role of adenosine kinase in atherosclerosis
腺苷激酶在动脉粥样硬化中的作用
- 批准号:
8183795 - 财政年份:2011
- 资助金额:
$ 46.37万 - 项目类别: