Macromolecular Substrates For Enzymes

酶的大分子底物

• 批准号: 6675236
• 负责人: GLEN HORTIN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6675236
• 关键词: allosteric site; chemical structure; chemical synthesis; clinical research; crosslink; diagnosis design /evaluation; diagnosis quality /standard; disease /disorder etiology; enzyme activity; enzyme substrate; human tissue; macromolecule; polymers; thrombin

Measurements of enzyme activity serve as important tools for the diagnosis of disease processes and for basic research. We are seeking to develop new substrates for enzymes that improve the ability to measure or the specificity of measuring enzyme activity. We have found that linking small chromogenic and fluorogenic substrates to polymer molecules serves as an approach to prepare substrates with large molecular size. Initial results were described in Clinical Chemistry 2001;47:215-222. Continuing studies have examined further models analyzing effects of substrate size on enzyme activity. These studies have examined effects of substrate size on antibody inhibition of enzyme activity (J Clin Lab Anal 2001;15:64-70) and on the activity of enzymes that have an active site located within a tubular structure that serve as a size-dependent filter using proteasomes as a model (J Prot Chem 2002;21:333-337.) We have been working on better physical characterization of the size of the new synthetic substrates using light scattering techniques and development of substrates for other classes of proteases such as metalloproteases.

酶活性的测量是疾病过程诊断和基础研究的重要工具。我们正在寻求开发新的酶底物，以提高测量酶活性的能力或特异性。我们发现，将小的显色和荧光底物与聚合物分子连接可以作为制备大分子大小底物的方法。临床化学2001；47:215-222描述了初步结果。持续的研究检验了进一步的模型，分析底物大小对酶活性的影响。这些研究考察了底物大小对抗体抑制酶活性的影响（J clinin Lab Anal 2001;15:64-70），以及以蛋白酶体为模型，在管状结构中具有活性位点的酶的活性（J Prot Chem 2002;21:33 -337）。我们一直致力于利用光散射技术对新合成底物的尺寸进行更好的物理表征，并开发其他类型蛋白酶（如金属蛋白酶）的底物。

项目成果

Substrate size selectivity of 20S proteasomes: analysis with variable-sized synthetic substrates.

20S 蛋白酶体的底物尺寸选择性：使用可变尺寸的合成底物进行分析。

• DOI: 10.1023/a:1019990201364
• 发表时间: 2002
• 期刊: Journal of protein chemistry
• 作者: Hortin,GlenL;Murthy,Jay
• 通讯作者: Murthy,Jay