CCR5 & CXCR4 Antagonist & Agonist Binding Site Structure
CCR5
基本信息
- 批准号:7354111
- 负责人:
- 金额:$ 34.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-02-01 至 2010-01-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAffinityAgonistAmino Acid SequenceAmino AcidsAnti-HIV AgentsAntibodiesBacteriophagesBindingBinding SitesBioinformaticsCCR5 geneCD4 Positive T LymphocytesCXCR4 geneCellsChemokine (C-C Motif) Receptor 5ComplexCyanogen BromideDataDevelopmentDrug resistanceEpitope MappingEpitopesHIVHIV Envelope Protein gp120HIV InfectionsHelix (Snails)Immunologic Deficiency SyndromesInfectionInflammationLabelLeadLengthMapsMass Spectrum AnalysisMeasuresModelingMolecular ConformationMonoclonal AntibodiesMutateN-terminalOpportunistic InfectionsPeptide MappingPeptide Sequence DeterminationPeptidesPersonsPharmaceutical PreparationsPharmacologic SubstancePositioning AttributeProcessRANTESRandom Peptide LibrariesRhodopsinRoleSiteSite-Directed MutagenesisStagingStromal Cell-Derived Factor 1StructureSurfaceT-Cell DevelopmentTechniquesTestingToxic effectVariantViralViral PhysiologyVirusVirus DiseasesWorkanalogchemokine receptorcrosslinkcytokinedesigndrug developmentear helixextracellularimprintimprovedpreferencereceptorreceptor bindingreceptor functionresearch studysmall moleculetool
项目摘要
DESCRIPTION (provided by applicant):
Problems of drug resistance, latent viral reservoirs, and the toxic effects of current anti-HIV drugs call for the development of new anti-retrovirals with different modes of action. A promising approach for drug development is interference with the entry of HIV into cells. HIV entry is a complex process that requires binding of the HIV envelope protein gp120 to a cellular co-receptor (CCR5 or CXCR4). This proposal seeks to enhance understanding of the structure of CCR5 and CXCR4, including the amino acid residues that contribute to alternative modes of antagonist binding and contact residues involved in agonist activation. Virus isolates that require CCR5 for entry are the predominant infectious forms of HIV transmitted from one person to another. Virus strains that require CXCR4 for entry often emerge in the late stages of infection, are considered to be more pathogentic, and correlate with severe loss of CD4+ T lymphocytes and the development of opportunistic infections due to severe immunodeficiency. Several small-molecule antagonists for CCR5 or CXCR4 that block virus infection have been identified as promising drug leads by pharmaceutical companies, but their binding sites on the receptors and the mechanism of HIV blocking are poorly understood. This project will use high-affinity photoactive analogs of antagonist and agonist molecules to examine the interaction sites in CCR5 and CXCR4-and will investigate the roles of the residues at the crosslinking sites by site-specific mutagenesis. We will also investigate the changes in the conformation of CCR5 that result in activation or antagonism of HIV binding, by studying the interaction sites of monoclonal antibodies specific for the antagonist- or agonist-bound conformations of CCR5. The proposed studies will lead to a better understanding of the structure and function of CCR5 and CXCR4 and aim to provide information useful for the design of more potent drugs that inhibit HIV entry while minimizing side effects due to activating or blocking normal functions of CCR5 and CXCR4.
描述(由申请人提供):
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 }}
EDWARD A DRATZ其他文献
EDWARD A DRATZ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('EDWARD A DRATZ', 18)}}的其他基金
CENTER FOR THE ANALYSIS OF CELLULAR MECHANISMS AND SYSTEMS BIOLOGY
细胞机制和系统生物学分析中心
- 批准号:
8359565 - 财政年份:2011
- 资助金额:
$ 34.65万 - 项目类别:
CENTER FOR THE ANALYSIS OF CELLULAR MECHANISMS AND SYSTEMS BIOLOGY
细胞机制和系统生物学分析中心
- 批准号:
8167555 - 财政年份:2010
- 资助金额:
$ 34.65万 - 项目类别:
Center for the Analysis of Cellular Mechanisms and Systems Biology
细胞机制和系统生物学分析中心
- 批准号:
7901876 - 财政年份:2009
- 资助金额:
$ 34.65万 - 项目类别:
CENTER FOR THE ANALYSIS OF CELLULAR MECHANISMS AND SYSTEMS BIOLOGY
细胞机制和系统生物学分析中心
- 批准号:
7960476 - 财政年份:2009
- 资助金额:
$ 34.65万 - 项目类别:
Center for the Analysis of Cellular Mechanisms and Systems Biology
细胞机制和系统生物学分析中心
- 批准号:
8605372 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
Multiplex Fluorescent Zdyes for Differential Glycomic Detection
用于差异糖组检测的多重荧光 Zdyes
- 批准号:
7395128 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
Multiplex Fluorescent Zdyes for Differential Glycomic Detection
用于差异糖组检测的多重荧光 Zdyes
- 批准号:
7944483 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
CENTER FOR THE ANALYSIS OF CELLULAR MECHANISMS AND SYSTEMS BIOLOGY
细胞机制和系统生物学分析中心
- 批准号:
7721041 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
Multiplex Fluorescent Zdyes for Differential Glycomic Detection
用于差异糖组检测的多重荧光 Zdyes
- 批准号:
7577536 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
Center for the Analysis of Cellular Mechanisms and Systems Biology
细胞机制和系统生物学分析中心
- 批准号:
7692996 - 财政年份:2008
- 资助金额:
$ 34.65万 - 项目类别:
相似海外基金
Discovery of a High Affinity, Selective and β-arrestin Biased 5-HT7R Agonist
发现高亲和力、选择性和β-抑制蛋白偏向的 5-HT7R 激动剂
- 批准号:
10412227 - 财政年份:2022
- 资助金额:
$ 34.65万 - 项目类别:
Discovery of a High Affinity, Selective and β-arrestin Biased 5-HT7R Agonist
发现高亲和力、选择性和β-抑制蛋白偏向的 5-HT7R 激动剂
- 批准号:
10610473 - 财政年份:2022
- 资助金额:
$ 34.65万 - 项目类别:
Supplement to Discovery of a high affinity, selective and beta-arrestinbiased 5-HT7R Agonist Grant
对高亲和力、选择性和 β 抑制偏向 5-HT7R 激动剂发现的补充补助金
- 批准号:
10799162 - 财政年份:2022
- 资助金额:
$ 34.65万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6639179 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6724797 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6636512 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6326889 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6266928 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6539099 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6520329 - 财政年份:2001
- 资助金额:
$ 34.65万 - 项目类别: