Binz H Kaspar, Amstutz Patrick, Plückthun Andreas
Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Nat Biotechnol. 2005 Oct;23(10):1257-68. doi: 10.1038/nbt1127.
Not all adaptive immune systems use the immunoglobulin fold as the basis for specific recognition molecules: sea lampreys, for example, have evolved an adaptive immune system that is based on leucine-rich repeat proteins. Additionally, many other proteins, not necessarily involved in adaptive immunity, mediate specific high-affinity interactions. Such alternatives to immunoglobulins represent attractive starting points for the design of novel binding molecules for research and clinical applications. Indeed, through progress and increased experience in library design and selection technologies, gained not least from working with synthetic antibody libraries, researchers have now exploited many of these novel scaffolds as tailor-made affinity reagents. Significant progress has been made not only in the basic science of generating specific binding molecules, but also in applications of the selected binders in laboratory procedures, proteomics, diagnostics and therapy. Challenges ahead include identifying applications where these novel proteins can not only be an alternative, but can enable approaches so far deemed technically impossible, and delineate those therapeutic applications commensurate with the molecular properties of the respective proteins.
例如，海七鳃鳗进化出了一种基于富含亮氨酸重复序列蛋白的适应性免疫系统。此外，许多其他蛋白质（不一定参与适应性免疫）介导特异性高亲和力相互作用。这些免疫球蛋白的替代物是设计用于研究和临床应用的新型结合分子的有吸引力的起点。事实上，通过在文库设计和筛选技术方面取得的进展以及积累的经验（尤其是通过合成抗体文库的研究获得的），研究人员现在已经将许多这些新型支架用作定制的亲和试剂。不仅在生成特异性结合分子的基础科学方面取得了重大进展，而且在所选结合剂在实验室程序、蛋白质组学、诊断和治疗中的应用方面也取得了重大进展。未来的挑战包括确定这些新型蛋白质不仅可以作为替代物，而且能够实现迄今为止被认为技术上不可能的方法的应用，并确定与各自蛋白质的分子特性相称的治疗应用。
