CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies

职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂

基本信息

  • 批准号:
    2339201
  • 负责人:
  • 金额:
    $ 60.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2024
  • 资助国家:
    美国
  • 起止时间:
    2024-02-01 至 2029-01-31
  • 项目状态:
    未结题

项目摘要

Antibodies are created by the immune system. They recognize foreign infectious agents. Their molecular recognition capabilities make them ideal to sense and to treat diseases. They are, however, not useful in binding to and blocking the action of proteases. This is important because protease activity can trigger the development of cancers. Key proteases involved in cancer development, called matrix metalloproteases (MMPs), are overproduced during the development of cancer and during diabetes, for example. The objective of this project is to evaluate the impact of modifying antibodies with unique amino acids on the regulation of MMP activity. The education component of this proposal seeks to enhance the Tufts STEM Ambassadors program and strengthen a partnership with the biotechnology program of an area vocational/technical high school.Extracellular proteases and peptidases play key roles in human health and disease. The specific disruption of these enzymes remains a fundamental challenge. For example, matrix metalloproteinases (MMPs) play key roles in development, inflammation, cancer, and infectious disease. Highly specific inhibitors are essential for uncovering the molecular functions of enzymes and for establishing a new generation of inhibitors with improved therapeutic potential. The overall goal is to establish principles of “chemically diversified” antibodies that enable next-generation protease inhibitor discovery. This project will evaluate integration of noncanonical amino acids and yeast display technology to exploit covalent (irreversible) binding and metal binding functionalities within antibodies. The investigators hope to discover chemistries capable of interfering with enzyme functions. These studies could also identify use cases where adding chemistries to antibodies leads to inhibitors with properties (such as potency, duration of action, or specific epitope targeting) that cannot be engineered into conventional antibodies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
抗体是由免疫系统产生的。它们能识别外来传染源。它们的分子识别能力使它们成为检测和治疗疾病的理想选择。然而,它们不能用于结合蛋白酶和阻断蛋白酶的作用。这一点很重要,因为蛋白酶活性可以引发癌症的发展。参与癌症发展的关键蛋白酶,称为基质金属蛋白酶(MMPs),在癌症发展期间和糖尿病期间过度产生。该项目的目的是评估用独特氨基酸修饰抗体对MMP活性调节的影响。该提案的教育部分旨在加强塔夫茨STEM大使计划,并加强与地区职业/技术高中生物技术计划的伙伴关系。细胞外蛋白酶和肽酶在人类健康和疾病中发挥着关键作用。这些酶的特定破坏仍然是一个根本性的挑战。例如,基质金属蛋白酶(MMP)在发育、炎症、癌症和感染性疾病中起关键作用。高度特异性的抑制剂对于揭示酶的分子功能和建立具有改进的治疗潜力的新一代抑制剂是必不可少的。总体目标是建立“化学多样化”抗体的原则,使下一代蛋白酶抑制剂的发现。该项目将评估非规范氨基酸和酵母展示技术的整合,以利用抗体内的共价(不可逆)结合和金属结合功能。研究人员希望发现能够干扰酶功能的化学物质。这些研究还可以确定在抗体中添加化学物质导致抑制剂具有无法工程化到传统抗体中的特性(例如效力、作用持续时间或特异性表位靶向)的用例。该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。

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 }}

James Van Deventer其他文献

James Van Deventer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('James Van Deventer', 18)}}的其他基金

Engineering and intracellular delivery of recombinant antibodies
重组抗体的工程设计和细胞内递送
  • 批准号:
    1807415
  • 财政年份:
    2018
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
EAGER: High throughput inhibitor discovery for dissecting serine hydrolase function
EAGER:用于剖析丝氨酸水解酶功能的高通量抑制剂的发现
  • 批准号:
    1815022
  • 财政年份:
    2018
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Standard Grant

相似国自然基金

Next Generation Majorana Nanowire Hybrids
  • 批准号:
  • 批准年份:
    2020
  • 资助金额:
    20 万元
  • 项目类别:

相似海外基金

CAREER: Next-generation Logic, Memory, and Agile Microwave Devices Enabled by Spin Phenomena in Emergent Quantum Materials
职业:由新兴量子材料中的自旋现象实现的下一代逻辑、存储器和敏捷微波器件
  • 批准号:
    2339723
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
CAREER: Securing Next-Generation Transportation Infrastructure: A Traffic Engineering Perspective
职业:保护下一代交通基础设施:交通工程视角
  • 批准号:
    2339753
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Standard Grant
CAREER: Next-Generation Methods for Statistical Integration of High-Dimensional Disparate Data Sources
职业:高维不同数据源统计集成的下一代方法
  • 批准号:
    2422478
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
CAREER: LoRa Enabled Space-air-ground Integrated Networks for Next-Generation Agricultural IoT
职业生涯:LoRa 支持下一代农业物联网的天地一体化网络
  • 批准号:
    2338976
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
CAREER: Next Generation Online Resource Allocation
职业:下一代在线资源分配
  • 批准号:
    2340306
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Standard Grant
CAREER: Next-Generation Flow Cytometry - A New Approach to Cell Heterogeneity
职业:下一代流式细胞术 - 细胞异质性的新方法
  • 批准号:
    2422750
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Standard Grant
CAREER: Non-Local Metamaterials and Metasurfaces for Next Generation Non-Reciprocal Acoustic Devices
职业:下一代非互易声学器件的非局域超材料和超表面
  • 批准号:
    2340782
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Standard Grant
CAREER: Next Generation of High-Level Synthesis for Agile Architectural Design (ArchHLS)
职业:下一代敏捷架构设计高级综合 (ArchHLS)
  • 批准号:
    2338365
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
CAREER: Engineering next-generation adrenal gland organoids
职业:设计下一代肾上腺类器官
  • 批准号:
    2335133
  • 财政年份:
    2024
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
CAREER: Next-generation Rhizosphere Monitoring - Non-invasive Plant Phenotyping and Health Monitoring Using the Light-piping Properties of Plant Stems
职业:下一代根际监测 - 利用植物茎的光管特性进行非侵入性植物表型和健康监测
  • 批准号:
    2238365
  • 财政年份:
    2023
  • 资助金额:
    $ 60.82万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了