Mirror image proteins.

Mirror image proteins.
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DOI:
10.1016/j.cbpa.2014.09.019
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发表时间:
2014-10
影响因子:
7.8
通讯作者:
Lu W
Lu W
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao L;Lu W

文献摘要

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完全由非天然D-氨基酸和非手性氨基酸甘氨酸组成的蛋白质是其天然L蛋白质的镜像形式。最近在化学蛋白质合成方面的进展提供了独特和方便的合成途径来获得结构域大小的镜像D-蛋白质,使蛋白质研究能够通过“镜子”以以前无法获得的方式进行。D-蛋白可以帮助确定其天然的难以结晶的L形式的结构(外消旋X射线结晶学);D-蛋白可以作为文库筛选的诱饵,最终产生药理上优越的D-肽/D-蛋白疗法(镜像噬菌体展示);D-蛋白也可以被用作探测生物学分子事件的强大机制工具。本文综述了镜像蛋白在结构生物学、药物开发和免疫学中的应用进展。
Proteins composed entirely of unnatural D-amino acids and the achiral amino acid glycine are mirror image forms of their native L-protein counterparts. Recent advances in chemical protein synthesis afford unique and facile synthetic access to domain-sized mirror image D-proteins, enabling protein research to be conducted through “the looking glass” and in a way previously unattainable. D-proteins can facilitate structure determination of their native L-forms that are difficult to crystallize (racemic X-ray crystallography); D-proteins can serve as the bait for library screening to ultimately yield pharmacologically superior D-peptide/D-protein therapeutics (mirror image phage display); D-proteins can also be used as a powerful mechanistic tool for probing molecular events in biology. This review examines recent progress in the application of mirror image proteins to structural biology, drug discovery, and immunology.