Engineering novel binding proteins from nonimmunoglobulin domains

  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.

 　 并不是所有的获得性免疫系统都是利用免疫球蛋白来特异的识别外来分子，例如七鳃鳗，它利用的是一种富亮氨酸的蛋白。此外，还有很多蛋白也调节高亲和力的特异相互作用，当然并不一定是获得性免疫系统中的。这些可以作为免疫球蛋白替代物的分子启发我们去设计新的结合分子，应用于科研和临床。事实上，随着库的设计和筛选技术的不断进步及经验的积累，研究人员不仅仅是从人工抗体库中，还开发了很多新的平台来进行高亲和力特定结合分子的设计。不仅在基础研究方面取得的突破，还将其应用到实验手段、蛋白组学、诊断学及疾病治疗中。当前所面临的挑战包括鉴别这些蛋白不仅可作为替代物，而且能使方法在技术上可行，以及描绘出的这些蛋白在治疗上的应用要与其分子特征相符。

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