Inserm U618 Protéases et Vectorisation Pulmonaires, IFR 135 Imagerie Fonctionnelle, University of Tours, 37000 Tours, France.
Biochimie. 2010 Nov;92(11):1689-704. doi: 10.1016/j.biochi.2010.05.003. Epub 2010 May 12.
Since its introduction by Georges Smith some 25 years ago, phage display has proved to be a powerful molecular technique for selecting proteins with desired biological properties from huge libraries. Early on, various protease inhibitor scaffolds were displayed at the surface of filamentous phages to select new inhibitors with shifted specificities and enhanced affinities towards one or more target protease(s). The past two decades have seen a number of natural protease inhibitors subjected to phage display, mostly to shift and increase their inhibitory specificity, but also to explore the molecular mechanisms by which they interact with their cognate enzymes with low or very high selectivity. This review focuses on the major uses of phage display in the field of protein protease inhibitors. The exquisite molecular mechanisms by which natural protease inhibitors prevent unwanted or excessive proteolysis in cells and tissues are also examined along with some of the general principles underlying the way phage display is applied to these molecules.
自 25 年前 Georges Smith 引入噬菌体展示技术以来，该技术已被证明是一种从庞大文库中筛选具有所需生物学特性的蛋白质的强大分子技术。早期，各种蛋白酶抑制剂支架被展示在丝状噬菌体的表面，以筛选具有不同特异性和增强对一种或多种靶蛋白酶亲和力的新型抑制剂。在过去的二十年中，已经有许多天然蛋白酶抑制剂被用于噬菌体展示，主要是为了改变和提高它们的抑制特异性，但也探索了它们与同源酶相互作用的分子机制，具有低或非常高的选择性。本综述重点介绍了噬菌体展示在蛋白质蛋白酶抑制剂领域的主要用途。还检查了天然蛋白酶抑制剂在细胞和组织中防止不必要或过度蛋白水解的精细分子机制，以及噬菌体展示应用于这些分子的一些一般原则。
