公开(公告)号：WO2013113851A1

公开(公告)日：2013-08-08

申请号：PCT/EP2013/051962

申请日：2013-01-31

Applicant: TECHNISCHE UNIVERSITAET MUENCHEN

Inventor： SKERRA, Arne ,  MEINING, Winfried ,  EGGENSTEIN, Evelyn

IPC: C07K14/47

CPC classification number: C07K14/47 ,  A61K38/00 ,  C07K14/8114 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/50 ,  C40B40/10

Abstract: The present disclosure relates to a collection of novel muteins derived from human α1m (or a1m) polypeptide or a functional homologue thereof. The disclosure further refers to a α1m mutein capable of specifically binding to one or more targets other than a target to which wild-type α1m binds. The disclosure also relates to a method for producing such collection of muteins and a method for isolating a mutein capable of binding one or more such non-natural targets of wild-type α1m polypeptide. These aspects are made possible due to, e.g, the structural elucidation of α1m disclosed herein by the present inventors, an appreciation of ligand-binding sights thereof and, hence, an understanding of which amino acid positions are most suitable for mutagenesis for re-engineering specificity and affinity for any given target while maintaining the secondary and/or tertiary structure of a1m.

Abstract translation: 本公开涉及衍生自人α1m（或a1m）多肽或其功能同系物的新型突变蛋白的集合。 本公开还涉及能够特异性结合野生型α1m结合的靶以外的一种或多种目标的α1突变蛋白。 本公开还涉及用于产生这种突变蛋白的收集的方法和分离能够结合野生型α1m多肽的一种或多种这种非天然靶标的突变蛋白的方法。 这些方面由于例如本发明人在此公开的α1m的结构阐释，配体结合瞄准物的鉴定以及因此理解哪种氨基酸位置最适于诱变用于重新设计而成为可能 特异性和亲和力，同时维持a1m的二级和/或三级结构。