公开(公告)号：US20110224135A1

公开(公告)日：2011-09-15

申请号：US13057809

申请日：2009-08-10

申请人： Heinrich Terlau ,  Rocio Finol-Urdaneta ,  Stefan Becker ,  Walter Raasch

发明人： Heinrich Terlau ,  Rocio Finol-Urdaneta ,  Stefan Becker ,  Walter Raasch

IPC分类号： A61K38/17 ,  C07K14/435 ,  C12Q1/02 ,  C07K1/107 ,  A61P3/10 ,  A61P3/04 ,  A61P3/00 ,  A61P9/12

CPC分类号： C07K14/43504 ,  C07K14/8114

摘要： The present invention relates to a (poly)peptide or a peptidomimetic thereof having the biological activity of Conkunitzin-S1, wherein said (poly)peptide is selected from (a) a polypeptide comprising or having the amino acid sequence of SEQ ID NO: 1; (b) a polypeptide having at least 85% sequence identity to SEQ ID NO:1; or (c) a fragment of a) or b); wherein said (poly)peptide or peptidomimetic specifically modulates the activity of a channel having the activity of a Kv1.7 containing channel, for the treatment or prevention of metabolic diseases or conditions, or secondary diseases or conditions related to said metabolic diseases or conditions. The present invention furthermore relates to a method of screening for (poly)peptides derived from Conkunitzin-S1 suitable for specifically modulating the activity of a channel having the activity of a Kv1.7 containing channel, comprising: (a) altering the amino acid sequence of Conkunitzin-S1 represented by SEQ ID NO: 1 by deleting and/or inserting and/or replacing at least one amino acid; and (b) determining the modulatory effect of the (poly)peptide obtained in step (a) (i) on a channel having the activity of a Kv1.7 containing channel and (ii) on channels, preferably potassium channels, not having the activity of a Kv1.7 containing channel, which are optionally expressed on the same cell as the channel having the activity of a Kv1.7 containing channel.

摘要翻译： 本发明涉及具有Conkunitzin-S1生物活性的（多）肽或其肽模拟物，其中所述（多）肽选自（a）包含或具有SEQ ID NO：1的氨基酸序列的多肽 ; （b）与SEQ ID NO：1具有至少85％序列同一性的多肽; 或（c）a）或b）的片段; 其中所述（多）肽或肽模拟物特异性调节具有Kv1.7含有通道活性的通道的活性，用于治疗或预防代谢疾病或病症，或与所述代谢疾病或病症有关的继发性疾病或病症。 本发明还涉及一种筛选衍生自Conkunitzin-S1的（多）肽的方法，其适用于特异性调节含有Kv1.7含有通道活性的通道的活性，其包括：（a）改变氨基酸序列 通过删除和/或插入和/或替换至少一个氨基酸的由SEQ ID NO：1表示的Conkunitzin-S1; （b）确定步骤（a）（i）中获得的（多）肽对具有Kv1.7含有通道活性的通道的调节作用，和（ii）在不具有 包含Kv1.7的通道的活性，其任选地在与具有含有Kv1.7的通道的活性的通道相同的单元上表达。