蛋白骨架在随机肽库构建及靶分子筛选中的应用*

自然界有着丰富的蛋白骨架来源。选择适宜的蛋白骨架和展示、筛选方法，可构建基于合理蛋白骨架结构的优化限制性随机肽库。与非限制性随机肽库相比，可望获得针对靶分子具有新功能的蛋白结构或更高亲和力的配体分子。目前，骨架蛋白限制的随机肽库已在高效靶分子筛选、基础研究、临床诊断和医学治疗等方面显示出巨大的潜在应用价值。以S-S限制性骨架、抗体分子、锌指蛋白、Z结构域、FN3结构域等为主要代表，综合介绍了蛋白骨架的结构基础、分类、基于蛋白骨架的限制性随机肽库构建及近年来在靶分子筛选等方面的应用最新进展。

Application of Scaffolds in Construction of Random Peptide Libraries and Targeted Molecules Selection

Nature is abundant in protein scaffolds. By selecting suitable protein scaffold, display and screening methods, the rational and constrained random peptide library(RPL) can be constructed. Compared with the non-constrained RPL, it offered more opportunities for obtaining novel protein structures and more higher affinity ligands against the target molecules. At present, the protein scaffold constrained RPLs have been shown great potential in applications such as target selection, basic research, clinical diagnosis, medical therapy and so on.It is systematically introduced the structure bases, classification and construction of constrained RPL based on scaffolds, as well the recent great advances of application in selection against target molecules with S-S constrained scaffolds, antibodies, Zinc finger protein, Z domain, FN3 domain as important examples.