Protease Substrate Array

蛋白酶底物阵列

• 批准号: 6924558
• 负责人: MICHAL LEBL
• 金额: $ 60.31万
• 依托单位: ILLUMINA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924558
• 关键词: apoptosis; cell line; endopeptidases; enzyme activity; enzyme substrate; enzyme substrate complex; fiber optics; fluorescence; high throughput technology; microarray technology; microcapsule; oligonucleotides; peptides; protease inhibitor; protein quantitation /detection; proteomics; technology /technique development

DESCRIPTION (provided by applicant): This proposal seeks to develop a new bead-based array technology for simultaneously measuring catalytic activity of proteases in small volumes of cells or biological fluids. Technology of this kind is needed to accelerate research in proteomics-based diagnostics and drug discovery by enabling molecular phenotyping across large populations, and the large-scale, massively parallel screening for drug leads, which modulate protease activity. Methods will be developed that allow multiplexed protease assays to be carried out on populations on beads, with each bead-type of the population being specific to a particular protease. Basic and diagnostic applications of this technology will enable careful examination of the molecular basis of cardiovascular disease, cancer, infectious disease, and certain genetic disorders, as well as the screening for and identification of protease inhibitors, which may interfere with pathogenic aberrations of such proteases. An advantage of such multiplexed enzyme assay format is the ability to screen for inhibitors, as well as specificity of inhibition in the same screen.

描述（由申请人提供）：该提案旨在开发一种新的基于珠的阵列技术，用于同时测量小体积细胞或生物流体中蛋白酶的催化活性。需要这种技术来加速基于蛋白质组学的诊断和药物发现的研究，使分子表型在大规模人群中，以及大规模，大规模平行筛选药物先导，调节蛋白酶活性。将开发允许对珠粒上的群体进行多重蛋白酶测定的方法，其中群体的每种珠粒类型对特定蛋白酶具有特异性。该技术的基本和诊断应用将能够仔细检查心血管疾病、癌症、传染病和某些遗传疾病的分子基础，以及筛选和鉴定可能干扰这些蛋白酶的致病性畸变的蛋白酶抑制剂。这种多重酶测定形式的优点是筛选抑制剂的能力，以及在相同筛选中抑制的特异性。

项目成果

Retention of histidine-containing peptides on a nickel affinity column.

含组氨酸肽在镍亲和柱上的保留。

• DOI: 10.1093/chromsci/45.4.207
• 发表时间: 2007
• 期刊: Journal of chromatographic science
• 影响因子: 1.3
• 作者: Kozlov,IgorA;Kermani,BahramG;Melnyk,PeterC;Barker,DavidL;Zhao,Chanfeng;Hachmann,JohnP;Lebl,Michal
• 通讯作者: Lebl,Michal

Using Support Vector Machine Regression to Model the Retention of Peptides in Immobilized Metal-affinity Chromatography.

• DOI: 10.1016/j.snb.2007.02.004
• 发表时间: 2007-07
• 期刊: Sensors and actuators. B, Chemical
• 作者: B. Kermani;Igor A. Kozlov;Peter C. Melnyk;Chanfeng Zhao;John P. Hachmann;David L. Barker;Michal Lebl

A method for rapid protease substrate evaluation and optimization.

一种快速蛋白酶底物评估和优化的方法。

• DOI: 10.2174/138620706777698535
• 发表时间: 2006
• 期刊: Combinatorial chemistry & high throughput screening
• 影响因子: 1.8
• 作者: Kozlov,IgorA;Melnyk,PeterC;Zhao,Chanfeng;Hachmann,JohnP;Shevchenko,Veronika;Srinivasan,Anu;Barker,DavidL;Lebl,Michal
• 通讯作者: Lebl,Michal

A high-complexity, multiplexed solution-phase assay for profiling protease activity on microarrays.

用于在微阵列上分析蛋白酶活性的高复杂性、多重溶液相测定。

• DOI: 10.2174/138620708783398304
• 发表时间: 2008
• 期刊: Combinatorial chemistry & high throughput screening
• 影响因子: 1.8
• 作者: Kozlov,IgorA;Melnyk,PeterC;Hachmann,JohnP;Srinivasan,Anu;Shults,Melissa;Zhao,Chanfeng;Musmacker,Joseph;Nelson,Nicholas;Barker,DavidL;Lebl,Michal
• 通讯作者: Lebl,Michal