The University of Chicago, Department of Biochemistry and Molecular Biology, Chicago, IL 60637, USA.
Biochemistry (Mosc). 2022 Jan;87(Suppl 1):S146-S110. doi: 10.1134/S0006297922140127.
Functional Protein Engineering became the hallmark in biomolecule manipulation in the new millennium, building on and surpassing the underlying structural DNA manipulation and recombination techniques developed and employed in the last decades of 20th century. Because of their prominence in almost all biological processes, proteins represent extremely important targets for engineering enhanced or altered properties that can lead to improvements exploitable in healthcare, medicine, research, biotechnology, and industry. Synthetic protein structures and functions can now be designed on a computer and/or evolved using molecular display or directed evolution methods in the laboratory. This review will focus on the recent trends in protein engineering and the impact of this technology on recent progress in science, cancer- and immunotherapies, with the emphasis on the current achievements in basic protein research using synthetic antibody (sABs) produced by phage display pipeline in the Kossiakoff laboratory at the University of Chicago (KossLab). Finally, engineering of the highly specific binding modules, such as variants of Streptococcal protein G with ultra-high orthogonal affinity for natural and engineered antibody scaffolds, and their possible applications as a plug-and-play platform for research and immunotherapy will be described.
功能蛋白质工程成为新千年生物分子操作的标志,建立在并超越了 20 世纪最后几十年发展和应用的基础结构 DNA 操作和重组技术。由于它们在几乎所有生物过程中的突出地位,蛋白质成为工程增强或改变特性的极其重要的目标,这些特性可以在医疗保健、医学、研究、生物技术和工业中得到利用。现在可以在计算机上设计合成蛋白质结构和功能,并且可以在实验室中使用分子展示或定向进化方法进行进化。本文将重点介绍蛋白质工程的最新趋势以及该技术对科学、癌症和免疫疗法的最新进展的影响,重点介绍芝加哥大学 Kossiakoff 实验室(KossLab)利用噬菌体展示技术生产的合成抗体(sAB)进行基础蛋白质研究的最新成果。最后,将描述高度特异性结合模块的工程设计,例如具有超高正交亲和力的链球菌蛋白 G 变体,用于天然和工程抗体支架,以及它们作为研究和免疫疗法的即插即用平台的可能应用。