公开(公告)号：US20100239517A1

公开(公告)日：2010-09-23

申请号：US12682057

申请日：2008-10-08

申请人： Stephen Brocchini ,  Penny Bryant ,  Yuehua Cong ,  Ji-Won Choi ,  Antony Godwin ,  Keith Powell

发明人： Stephen Brocchini ,  Penny Bryant ,  Yuehua Cong ,  Ji-Won Choi ,  Antony Godwin ,  Keith Powell

IPC分类号： A61K38/21 ,  C07K16/00 ,  C07K14/56 ,  C07K14/47 ,  A61K38/17 ,  A61K39/44 ,  A61P29/00

CPC分类号： A61K47/645 ,  A61K47/60 ,  A61K47/65

摘要： The invention provides a novel process for conjugating a polymer, especially PEG, to a protein or peptide, which comprises reacting a polymeric conjugation reagent with a protein or peptide containing a polyhistidine tag under conditions such that conjugation occurs via said polyhistidine tag. The resulting conjugates are novel. The invention further relates to novel conjugates of the general formula (I) in which one of X and X′ represents a polymer, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; or, if X′ represents a polymer, X-Q-W— together may represent an electron withdrawing group; and in addition, if X represents a polymer, X′ and electron withdrawing group W together with the interjacent atoms may form a ring; Z represents a protein or a peptide linked to A and B via respective histidine residues; A is a C1-5 alkylene or alkenylene chain; and B is a bond or a C1-4 alkylene or alkenylene chain.

摘要翻译： 本发明提供了一种用于将聚合物，特别是PEG与蛋白质或肽共轭的新方法，其包括使聚合物缀合试剂与含有多组氨酸标签的蛋白质或肽在通过所述多组氨酸标签发生缀合的条件下反应。 所得到的缀合物是新颖的。 本发明还涉及通式（I）的新结合物，其中X和X'之一表示聚合物，另一个表示氢原子; 每个Q独立地表示连接基团; W表示吸电子部分或可通过还原吸电子部分制备的部分; 或者如果X'代表聚合物，则X-Q-W一起可以代表吸电子基团; 此外，如果X表示聚合物，则X'和吸电子基团W与中间原子一起可以形成环; Z表示通过相应组氨酸残基与A和B连接的蛋白质或肽; A是C 1-5亚烷基或亚烯基链; B是键或C1-4亚烷基或亚链烯基。