Macromolecular Substrates For Enzymes

酶活性的测量是诊断疾病过程和进行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，将小的显色底物和荧光底物连接到聚合物分子上是制备大分子尺寸底物的一种方法。初步结果发表在《临床化学》2001；47：215-222。持续的研究进一步检验了分析底物大小对酶活性影响的模型。这些研究考察了底物大小对抗体抑制酶活性的影响(J Clin Lab Anal2001；15：-70)，以及以蛋白酶体为模型(J Prot Chem 2002；21：333-337)，对活性部位位于管状结构内的酶的活性的影响(J Prot Chem 2002；21：333-337)。我们一直致力于利用光散射技术对新的合成底物的大小进行更好的物理表征，并开发其他类型的蛋白酶底物，如金属蛋白酶。

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.