Core C: Enzymology Core
核心 C:酶学核心
基本信息
- 批准号:10513682
- 负责人:
- 金额:$ 746.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-16 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Alberta provinceAlphavirusBacteriaBinding SitesBiochemicalBiochemistryBiological AssayBiophysicsCOVID-19 assayCellsCollaborationsCommunitiesComplexCoronavirusCryoelectron MicroscopyDevelopmentDistantEbola virusEnzymatic BiochemistryEnzyme InhibitionEnzyme KineticsEnzymesExhibitsFilovirusFlavivirusGenerationsGoalsHIV-1InsectaInternationalLaboratoriesLeadMammalian CellMeasurementMiniaturizationMonitorMultienzyme ComplexesMultiprotein ComplexesMutationNucleotidesPolymeraseProcessProtein FamilyRNA HelicaseRNA-Directed DNA PolymeraseRecordsResearch Project GrantsResistanceResistance developmentReverse Transcriptase InhibitorsSARS coronavirusStructureSystemTechnologyTestingTranslationsUniversitiesValidationViralVirusX-Ray Crystallographyantiviral drug developmentbiophysical techniquesdensitydrug developmentdrug discoveryhigh throughput screeninginhibitorinsightinterestlead optimizationmemberprogramsprotein expressionprotein purificationprotocol developmentscreeningsingle moleculestructural biologythree dimensional structuretoolvirology
项目摘要
ABSTRACT
The overarching goal of Core C is to support READDI-AC discovery efforts in collaboration with Discovery Core
B and MedChem Core D by validation, characterization, and optimization of compounds in enzyme assays and
structural studies, and to provide the Research Projects with detailed mechanisms of action and mechanistic
insights to mitigate potential problems with resistance conferring mutations.
Enzymology Core C includes seven internationally recognized laboratories that cover complementary expertise
at the interfaces of virology, biochemistry, biophysics and structural biology. Three specific aims that describe
the central activities of Enzymology Core C:
Aim 1: Develop assays to support hit discovery efforts by Discovery Core B.
Key activities include the expression and purification of enzymes that the Research Projects and Discovery
Core B have selected as targets. Enzymology Core C will support the development of protocols for the
expression and purification of new enzyme targets and their corresponding assays to monitor activity and
inhibition. The translation of enzyme assays into high density formats to facilitate high throughput screening by
Discovery Core B is a second responsibility.
Aim 2. Structural Biology to guide hit and lead optimization.
Enzymology Core C will focus on solving 3D structures of polymerases and RNA helicases that are currently
not available to the scientific community. Priority will also be given to solving the structures of flavivirus and
alphavirus polymerases in complex with the nucleotide and non-nucleotide analog inhibitors to provide detailed
information on the inhibitor binding sites.
Aim 3. Support the Projects in detailed mechanism of action studies for lead compounds.
Functional assays will be employed to assess the inhibitory activity against the biologically relevant enzyme
target, such as measurements of the half maximal inhibitory concentration to determine compound potency.
Promising hits and leads will also be tested against homologous enzymes within the protein family as well as
distant enzymes to assess breadth and the potential for off-target activity. Enzymology Core C will provide an
array of state-of-the-art biochemical/biophysical approaches to provide MedChem Core D and the Projects with
information on the mechanisms associated with inhibition and resistance.
摘要
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 }}
CRAIG E. CAMERON其他文献
CRAIG E. CAMERON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('CRAIG E. CAMERON', 18)}}的其他基金
Enteroviral 2C protein as a therapeutic target
肠道病毒2C蛋白作为治疗靶点
- 批准号:
10609524 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Enteroviral 2C protein as a therapeutic target
肠道病毒2C蛋白作为治疗靶点
- 批准号:
10450381 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Optimizing nucleoside analog efficacy with novel exonuclease inhibitors
使用新型核酸外切酶抑制剂优化核苷类似物的功效
- 批准号:
10514274 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Contribution of IL-32 gene expression to viral persistence
IL-32 基因表达对病毒持久性的贡献
- 批准号:
10057016 - 财政年份:2020
- 资助金额:
$ 746.26万 - 项目类别:
Contribution of IL-32 gene expression to viral persistence
IL-32 基因表达对病毒持久性的贡献
- 批准号:
10177863 - 财政年份:2020
- 资助金额:
$ 746.26万 - 项目类别:
相似海外基金
Intracellular functions and mechanisms of alphavirus ion channel 6K
甲病毒离子通道6K的细胞内功能和机制
- 批准号:
10727819 - 财政年份:2023
- 资助金额:
$ 746.26万 - 项目类别:
Elucidating the mechanisms of alphavirus subgenomic RNA translation
阐明甲病毒亚基因组 RNA 翻译机制
- 批准号:
10678281 - 财政年份:2023
- 资助金额:
$ 746.26万 - 项目类别:
Development of a Cross-Protective New World Encephalitic Alphavirus Subunit Vaccine
交叉保护性新世界脑炎甲病毒亚单位疫苗的研制
- 批准号:
10696914 - 财政年份:2023
- 资助金额:
$ 746.26万 - 项目类别:
Defining the Molecular Determinants of Encephalitic Alphavirus Viremia
定义脑炎甲病毒血症的分子决定因素
- 批准号:
10599124 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Defining the Molecular Determinants of Encephalitic Alphavirus Viremia
定义脑炎甲病毒血症的分子决定因素
- 批准号:
10384551 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Center of Excellence for Encephalitic Alphavirus Therapeutics
脑炎甲病毒治疗卓越中心
- 批准号:
10631703 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Mechanisms of alphavirus infectivity and adaptation - Resubmission - 1
甲病毒感染性和适应机制 - 重新提交 - 1
- 批准号:
10556424 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Structural Mechanisms of Alphavirus Membrane Fusion
甲病毒膜融合的结构机制
- 批准号:
10444088 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Structural Mechanisms of Alphavirus Membrane Fusion
甲病毒膜融合的结构机制
- 批准号:
10612929 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:
Mechanisms of alphavirus infectivity and adaptation - Resubmission - 1
甲病毒感染性和适应机制 - 重新提交 - 1
- 批准号:
10444392 - 财政年份:2022
- 资助金额:
$ 746.26万 - 项目类别:














{{item.name}}会员




