Construction and Biological Characterisation of a Custom Engineered Protein Degradation Tool

定制工程蛋白质降解工具的构建和生物学表征

基本信息

  • 批准号:
    1943410
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Studentship
  • 财政年份:
    2017
  • 资助国家:
    英国
  • 起止时间:
    2017 至 无数据
  • 项目状态:
    已结题

项目摘要

Development of non-small molecule drugs has expanded over recent years, with biologics such as antibodies now seen as a viable treatment for some diseases. Protein and peptide drugs benefit from higher specificities than small molecules, and there is a much wider range of targets to which they can be applied. One such target is Aurora Kinase A, which is overexpressed in many cancer types and acts as a driver of cancer by phosphorylating substrates. AURKA is overexpressed in cancers such as breast, colon and neuroblastomas and targeting AURKA by inhibition does affect cancer growth but there is not complete reversal of the cancer phenotype. Targeting AURKA for degradation using the ubiquitin-proteasome system has potential for a better clinical response. PROTACs (PROteolysis Targeting Chimeras) are a new class of drug, that induce degradation of target molecules via a bifunctional small molecule, with a flexible linker region in the middle. Degradation occurs via the Ubiquitin Proteasome System, using chains of ubiquitin as the signalling molecule. There are a range of scaffolds used in this work, including TetratrioPeptide Repeats, Recombinase ATPase domain, and Monobodies. These scaffold proteins have AURKA binding regions inserted and degrons that bind E3 ligases elsewhere in the sequence. These bifunctional molecules should induce Aurora A degradation using the Ubiquitin Proteasome System. Work has been preformed using cancer cells treated with these constructs, and biophysical work to characterise their structure and interactions.
近年来,非小分子药物的开发得到了扩展,抗体等生物制剂现在被视为治疗某些疾病的可行方法。蛋白质和多肽药物比小分子药物具有更高的特异性,并且它们可以应用的靶点范围更广。其中一个这样的靶点是极光激酶A,它在许多癌症类型中过度表达,并通过磷酸化底物作为癌症的驱动因素。AURKA在乳腺癌、结肠癌和神经母细胞瘤等癌症中过度表达,通过抑制靶向AURKA确实会影响癌症生长,但不会完全逆转癌症表型。利用泛素-蛋白酶体系统靶向AURKA降解有可能获得更好的临床反应。PROteolysis Targeting Chimeras (PROteolysis Targeting Chimeras, PROteolysis靶向嵌合体)是一类新的药物,它通过一个双功能小分子,在中间有一个灵活的连接区域来诱导目标分子的降解。降解通过泛素蛋白酶体系统发生,使用泛素链作为信号分子。在这项工作中使用了一系列支架,包括四肽重复序列,重组酶atp酶结构域和单体。这些支架蛋白插入和降解AURKA结合区域,结合序列中其他地方的E3连接酶。这些双功能分子应该通过泛素蛋白酶体系统诱导Aurora A降解。研究人员利用这些结构体处理过的癌细胞,并利用生物物理学来描述它们的结构和相互作用。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Construction and Biological Characterisation of Custom Engineered Protein Degradation Tools.
定制工程蛋白质降解工具的构建和生物学表征。
  • DOI:
    10.17863/cam.86674
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Stockton S
  • 通讯作者:
    Stockton S
{{ 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 }}

其他文献

Internet-administered, low-intensity cognitive behavioral therapy for parents of children treated for cancer: A feasibility trial (ENGAGE).
针对癌症儿童父母的互联网管理、低强度认知行为疗法:可行性试验 (ENGAGE)。
  • DOI:
    10.1002/cam4.5377
  • 发表时间:
    2023-03
  • 期刊:
  • 影响因子:
    4
  • 作者:
  • 通讯作者:
Differences in child and adolescent exposure to unhealthy food and beverage advertising on television in a self-regulatory environment.
在自我监管的环境中,儿童和青少年在电视上接触不健康食品和饮料广告的情况存在差异。
  • DOI:
    10.1186/s12889-023-15027-w
  • 发表时间:
    2023-03-23
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
  • 通讯作者:
The association between rheumatoid arthritis and reduced estimated cardiorespiratory fitness is mediated by physical symptoms and negative emotions: a cross-sectional study.
类风湿性关节炎与估计心肺健康降低之间的关联是由身体症状和负面情绪介导的:一项横断面研究。
  • DOI:
    10.1007/s10067-023-06584-x
  • 发表时间:
    2023-07
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
  • 通讯作者:
ElasticBLAST: accelerating sequence search via cloud computing.
ElasticBLAST:通过云计算加速序列搜索。
  • DOI:
    10.1186/s12859-023-05245-9
  • 发表时间:
    2023-03-26
  • 期刊:
  • 影响因子:
    3
  • 作者:
  • 通讯作者:
Amplified EQCM-D detection of extracellular vesicles using 2D gold nanostructured arrays fabricated by block copolymer self-assembly.
使用通过嵌段共聚物自组装制造的 2D 金纳米结构阵列放大 EQCM-D 检测细胞外囊泡。
  • DOI:
    10.1039/d2nh00424k
  • 发表时间:
    2023-03-27
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
  • 通讯作者:

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('', 18)}}的其他基金

An implantable biosensor microsystem for real-time measurement of circulating biomarkers
用于实时测量循环生物标志物的植入式生物传感器微系统
  • 批准号:
    2901954
  • 财政年份:
    2028
  • 资助金额:
    --
  • 项目类别:
    Studentship
Exploiting the polysaccharide breakdown capacity of the human gut microbiome to develop environmentally sustainable dishwashing solutions
利用人类肠道微生物群的多糖分解能力来开发环境可持续的洗碗解决方案
  • 批准号:
    2896097
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
A Robot that Swims Through Granular Materials
可以在颗粒材料中游动的机器人
  • 批准号:
    2780268
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Likelihood and impact of severe space weather events on the resilience of nuclear power and safeguards monitoring.
严重空间天气事件对核电和保障监督的恢复力的可能性和影响。
  • 批准号:
    2908918
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Proton, alpha and gamma irradiation assisted stress corrosion cracking: understanding the fuel-stainless steel interface
质子、α 和 γ 辐照辅助应力腐蚀开裂:了解燃料-不锈钢界面
  • 批准号:
    2908693
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Field Assisted Sintering of Nuclear Fuel Simulants
核燃料模拟物的现场辅助烧结
  • 批准号:
    2908917
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Assessment of new fatigue capable titanium alloys for aerospace applications
评估用于航空航天应用的新型抗疲劳钛合金
  • 批准号:
    2879438
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
使用右旋糖酐-胶原蛋白水凝胶开发 3D 打印皮肤模型,以分析白细胞介素 17 抑制剂的细胞和表观遗传效应
  • 批准号:
    2890513
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
CDT year 1 so TBC in Oct 2024
CDT 第 1 年,预计 2024 年 10 月
  • 批准号:
    2879865
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
  • 批准号:
    2876993
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship

相似海外基金

Biological and pathological characterisation of novel plasmid-carrying avian Chlamydia abortus strain 84/2334
新型质粒携带禽流产衣原体菌株 84/2334 的生物学和病理学特征
  • 批准号:
    BB/X016692/1
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Biological and pathological characterisation of novel plasmid-carrying avian Chlamydia abortus strain 84/2334
新型质粒携带禽流产衣原体菌株 84/2334 的生物学和病理学特征
  • 批准号:
    BB/X015483/1
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Developments and applications of cavity ring-down polarimetry for the detection and characterisation of optically active biological compounds.
用于检测和表征光学活性生物化合物的腔衰荡旋光法的开发和应用。
  • 批准号:
    2890146
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Studentship
Nanoscale Characterisation of Biological and Bioinspired Materials using Integrated Fluidic Force - High-Resolution Confocal Microscopy
使用集成流体力对生物和仿生材料进行纳米级表征 - 高分辨率共焦显微镜
  • 批准号:
    BB/W019639/1
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Going to the source: Terrestrial and freshwater environmental characterisation, monitoring, and biological fates of plastic pollution
追根溯源:陆地和淡水环境特征、监测以及塑料污染的生物归宿
  • 批准号:
    557769-2021
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Going to the source: Terrestrial and freshwater environmental characterisation, monitoring, and biological fates of plastic pollution
追根溯源:陆地和淡水环境特征、监测以及塑料污染的生物归宿
  • 批准号:
    557769-2021
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Systematic characterisation of genetically influenced 'omics' phenotypes and disease modules within biological networks
生物网络中受遗传影响的“组学”表型和疾病模块的系统表征
  • 批准号:
    MR/S003746/1
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
    Fellowship
Characterisation of biological nanopores for sensing and biopolymer sequencing
用于传感和生物聚合物测序的生物纳米孔表征
  • 批准号:
    BB/R505778/1
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Training Grant
Physical and biological characterisation of clinically relevant combined MRI-radiation exposures with conventional and nanoparticle contrast agents
常规和纳米颗粒造影剂临床相关联合 MRI 辐射暴露的物理和生物学特征
  • 批准号:
    MR/P01593X/1
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Training Grant
Physical and biological characterisation of clinically relevant combined MRI-radiation exposures with conventional and nanoparticle contrast agents
常规和纳米颗粒造影剂临床相关联合 MRI 辐射暴露的物理和生物学特征
  • 批准号:
    1934654
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了