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针对生物医学应用的小分子蛋白定制。

Tailoring small proteins towards biomedical applications.

机构信息

Department of Protein Engineering, University of Wroclaw, Tamka 2, 50-137 Wroclaw, Poland.

出版信息

Curr Pharm Biotechnol. 2011 Nov;12(11):1792-8. doi: 10.2174/138920111798376905.

DOI:10.2174/138920111798376905
PMID:21902634
Abstract

Over the last two decades proteins have become increasingly important in human therapy and diagnosis. Engineering therapeutic proteins through improving their biological activity and stability has been a major interest in our group. In this mini-review we summarize our research on three proteins with pharmaceutical potential - serine protease inhibitor from squash seeds (CMTI), bovine pancreatic trypsin inhibitor (BPTI), and human fibroblast growth factor 1 (FGF1). To improve the functional properties of these proteins we used multiple techniques such as homology approach, rational design, total chemical synthesis, site-directed mutagenesis and phage display. The physicochemical properties of the obtained protein variants were evaluated using protein crystallography, spectroscopic techniques, enzymatic assays, stability measurements as well as numerous biological tests.

摘要

在过去的二十年中,蛋白质在人类治疗和诊断中的作用越来越重要。通过提高其生物活性和稳定性来设计治疗性蛋白质一直是我们小组的主要关注点。在这篇小综述中,我们总结了我们在三种具有药物潜力的蛋白质方面的研究成果 - 来自南瓜种子的丝氨酸蛋白酶抑制剂(CMTI)、牛胰蛋白酶抑制剂(BPTI)和人成纤维细胞生长因子 1(FGF1)。为了改善这些蛋白质的功能特性,我们使用了多种技术,如同源性方法、理性设计、全化学合成、定点突变和噬菌体展示。使用蛋白质晶体学、光谱技术、酶促测定、稳定性测量以及许多生物学测试来评估获得的蛋白质变体的物理化学性质。

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