Modulation of Innate Immune Responses: Synthesis and Biological Studies of Homo- and Hetero-dimeric Pattern Recognition Receptor Agonists and Other Immunostimulants
先天免疫反应的调节:同源和异源二聚体模式识别受体激动剂和其他免疫刺激剂的合成和生物学研究
基本信息
- 批准号:RGPIN-2017-05363
- 负责人:
- 金额:$ 1.6万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2017
- 资助国家:加拿大
- 起止时间:2017-01-01 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Immune cells defend against microbial infection by detecting pathogen-associated molecular patterns (PAMPs) present on microbes via pattern recognition receptors. Harnessing signalling by targeting these receptors with small molecule immunostimulants could greatly benefit the development of effective therapeutic agents. Although a good number of immunostimulants are known to date, the translation of these molecules into clinical uses is challenging for a number of reasons, such as: (a) a lack of understanding of the exact mechanisms of their action, and thus the inability to precisely predict effects, (b) relatively low potency of some immunostimulants, and (c) toxic side effects of others. In this research, we propose to covalently link different immunostimulants in order to study the effects of particular combinations of such molecules on their immunological properties. Covalently linked dimeric ligands containing two immunostimulants can simultaneously target two receptors of the immune system. Such dimeric ligands thereby become more potent immune activating agents due to a synergistic effect between the two immunostimulants. A group of dimeric ligands comprised of several different types of immunostimulants and different lengths of linking spacers will be chemically synthesized. Biological studies using in vitro experiments will reveal the immunostimulatory activity of these compounds. This research will provide useful tools for binding immunostimulating molecules to study innate immune response to synthetic immunostimulants and the crosstalk mechanisms between receptors. Through chemical synthesis and biological studies, more potent immunostimulants with no toxic side effects will be discovered. The long term goal of this research is to discover novel immunostimulatory agents with high potency and defined immunological effects, which will provide useful molecular tools for health-related research and ultimately lead to the development of clinically useful therapeutic agents such as vaccine adjuvants.
免疫细胞通过模式识别受体检测微生物上存在的病原体相关分子模式(PAMPs)来防御微生物感染。利用小分子免疫刺激剂靶向这些受体,可以极大地促进有效治疗剂的开发。尽管迄今为止已知大量免疫刺激剂,但由于以下原因,将这些分子转化为临床应用具有挑战性,例如:(a)缺乏对其作用的确切机制的了解,因此无法精确预测效果;(b)某些免疫刺激剂的效力相对较低;(c)其他免疫刺激剂的毒副作用。在这项研究中,我们提出共价连接不同的免疫刺激剂,以研究这些分子的特定组合对其免疫特性的影响。含有两种免疫刺激剂的共价连接二聚体可以同时靶向免疫系统的两种受体。由于两种免疫刺激剂之间的协同作用,这种二聚体配体因此成为更有效的免疫激活剂。一组由几种不同类型的免疫刺激剂和不同长度的连接间隔组成的二聚体配体将被化学合成。使用体外实验的生物学研究将揭示这些化合物的免疫刺激活性。本研究将为结合免疫刺激分子来研究先天免疫对合成免疫刺激药物的应答和受体间的串扰机制提供有用的工具。通过化学合成和生物学研究,将会发现更强效、无毒副作用的免疫刺激剂。这项研究的长期目标是发现具有高效和明确免疫效应的新型免疫刺激剂,这将为与健康相关的研究提供有用的分子工具,并最终导致临床有用的治疗剂如疫苗佐剂的开发。
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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Jiang, ZiHua其他文献
Simultaneous determination of 9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate in rat plasma by UHPLC-ESI-MS/MS after administration of xiyanping injection: application to a pharmacokinetic study
- DOI:
10.1002/bmc.2866 - 发表时间:
2013-07-01 - 期刊:
- 影响因子:1.8
- 作者:
Chong, Lan;Chen, Weikang;Jiang, ZiHua - 通讯作者:
Jiang, ZiHua
Jiang, ZiHua的其他文献
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{{ truncateString('Jiang, ZiHua', 18)}}的其他基金
Modulation of Innate Immune Responses: Synthesis and Biological Studies of Homo- and Hetero-dimeric Pattern Recognition Receptor Agonists and Other Immunostimulants
先天免疫反应的调节:同源和异源二聚体模式识别受体激动剂和其他免疫刺激剂的合成和生物学研究
- 批准号:
RGPIN-2017-05363 - 财政年份:2022
- 资助金额:
$ 1.6万 - 项目类别:
Discovery Grants Program - Individual
Modulation of Innate Immune Responses: Synthesis and Biological Studies of Homo- and Hetero-dimeric Pattern Recognition Receptor Agonists and Other Immunostimulants
先天免疫反应的调节:同源和异源二聚体模式识别受体激动剂和其他免疫刺激剂的合成和生物学研究
- 批准号:
RGPIN-2017-05363 - 财政年份:2020
- 资助金额:
$ 1.6万 - 项目类别:
Discovery Grants Program - Individual
Modulation of Innate Immune Responses: Synthesis and Biological Studies of Homo- and Hetero-dimeric Pattern Recognition Receptor Agonists and Other Immunostimulants
先天免疫反应的调节:同源和异源二聚体模式识别受体激动剂和其他免疫刺激剂的合成和生物学研究
- 批准号:
RGPIN-2017-05363 - 财政年份:2019
- 资助金额:
$ 1.6万 - 项目类别:
Discovery Grants Program - Individual
Modulation of Innate Immune Responses: Synthesis and Biological Studies of Homo- and Hetero-dimeric Pattern Recognition Receptor Agonists and Other Immunostimulants
先天免疫反应的调节:同源和异源二聚体模式识别受体激动剂和其他免疫刺激剂的合成和生物学研究
- 批准号:
RGPIN-2017-05363 - 财政年份:2018
- 资助金额:
$ 1.6万 - 项目类别:
Discovery Grants Program - Individual
Synthetic lipo-MDP analogs as mucosal adjuvants for animal vaccines
合成脂-MDP类似物作为动物疫苗粘膜佐剂
- 批准号:
488280-2015 - 财政年份:2015
- 资助金额:
$ 1.6万 - 项目类别:
Engage Grants Program
Synthetic NOD-like receptor ligands for modulating immune responses
用于调节免疫反应的合成 NOD 样受体配体
- 批准号:
469917-2014 - 财政年份:2014
- 资助金额:
$ 1.6万 - 项目类别:
Engage Grants Program
Identification of collarborative research projects in discovering novel anti-infectious agents
发现新型抗感染药物的合作研究项目的确定
- 批准号:
451538-2013 - 财政年份:2013
- 资助金额:
$ 1.6万 - 项目类别:
Interaction Grants Program
Synthetic Toll-like Receptor 4 Agonists as Potential Adjuvants for Use in Animal Vaccines
合成 Toll 样受体 4 激动剂作为动物疫苗中的潜在佐剂
- 批准号:
428767-2011 - 财政年份:2011
- 资助金额:
$ 1.6万 - 项目类别:
Engage Grants Program
Synthetic toll-like receptor 4 ligands: synthesis and biochemical investigation of pseudomonas aeruginosa lipid As and analogues
合成Toll样受体4配体:铜绿假单胞菌脂质As及其类似物的合成和生化研究
- 批准号:
312630-2008 - 财政年份:2010
- 资助金额:
$ 1.6万 - 项目类别:
Discovery Grants Program - Individual
Exploring Research Partnership With A Company
探索与公司的研究合作伙伴关系
- 批准号:
408115-2010 - 财政年份:2010
- 资助金额:
$ 1.6万 - 项目类别:
Interaction Grants Program
相似国自然基金
Innate-likeB细胞受损介导凋亡细胞的清除障碍在系统性红斑狼疮发病中的作用及机制研究
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