Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Cell Chem Biol. 2016 May 19;23(5):543-553. doi: 10.1016/j.chembiol.2016.04.010.
Protein engineering is an emerging discipline that dovetails modern molecular biology techniques with high-throughput screening, laboratory evolution technologies, and computational approaches to modify sequence, structure, and, in some cases, function and properties of proteins. The ultimate goal is to develop new proteins with improved or designer functions for use in biotechnology, medicine, and basic research. One way to engineer proteins is to change their solvent-exposed regions through focused or random "protein resurfacing." In this review we explain what protein resurfacing is, and discuss recent examples of how this strategy is used to generate proteins with altered or broadened recognition profiles, improved stability, solubility, and expression, cell-penetrating ability, and reduced immunogenicity. Additionally we comment on how these properties can be further improved using chemical resurfacing approaches. Protein resurfacing will likely play an increasingly important role as more biologics enter clinical use, and we present some arguments to support this view.
蛋白质工程是一门新兴学科，它将现代分子生物学技术与高通量筛选、实验室进化技术和计算方法相结合，以修饰蛋白质的序列、结构，并在某些情况下修饰其功能和特性。其最终目标是开发具有改进或设计功能的新型蛋白质，用于生物技术、医学和基础研究。一种工程蛋白质的方法是通过有针对性或随机的“蛋白质表面重塑”来改变其暴露于溶剂的区域。在这篇综述中，我们解释了什么是蛋白质表面重塑，并讨论了最近如何利用这种策略来产生具有改变或拓宽识别谱、提高稳定性、溶解性和表达能力、穿透细胞能力以及降低免疫原性的蛋白质的例子。此外，我们还评论了如何使用化学表面重塑方法进一步改善这些特性。随着更多的生物制剂进入临床应用，蛋白质表面重塑可能会发挥越来越重要的作用，我们提出了一些论据来支持这一观点。
