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    • 3. 发明申请
    • USE OF CONKUNITZIN-S1 FOR THE MODULATION OF GLUCOSE-INDUCED INSULIN SECRETION
    • 用于调节葡萄糖诱导的胰岛素分泌的康宁嗪-S1
    • WO2010015421A1
    • 2010-02-11
    • PCT/EP2009/005801
    • 2009-08-10
    • MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V. BERLINUNIVERSITÄT ZU LÜBECKTERLAU, HeinrichFINOL-URDANETA, RocioBECKER, StefanRAASCH, Walter
    • TERLAU, HeinrichFINOL-URDANETA, RocioBECKER, StefanRAASCH, Walter
    • C07K14/435
    • C07K14/43504C07K14/8114
    • 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; wherein a modulatory effect of the (poly)peptide determined in step (i) that is at least 50% of the modulatory effect of Conkunitzin-S1 indicates that the (poly)peptide re suitable for modulating the activity of said channel having the activity of a Kv1.7 containing channel; and wherein the determination of essentially no modulatory effect in step (ii) indicates that the (poly)peptide is specifically modulating the activity of channels having the activity of a Kv1.7 containing channel.
    • 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 含有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细胞上表达; 其中在步骤(i)中测定的所述(多)肽的调节作用是Conkunitzin-S1的调节作用的至少50%,这表明(多)肽适合于调节具有活性的所述通道的活性 包含Kv1.7通道; 并且其中在步骤(ii)中基本上没有调节作用的测定表明(多)肽特异性调节具有含有Kv1.7的通道的活性的通道的活性。
    • 7. 发明公开
    • USE OF CONKUNITZIN-S1 FOR THE MODULATION OF GLUCOSE-INDUCED INSULIN SECRETION
    • CONKUNITZIN-S1的调制糖诱导INSULINSEZERNIERUNG的使用
    • EP2367848A1
    • 2011-09-28
    • EP09804528.9
    • 2009-08-10
    • Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.Universität zu Lübeck
    • TERLAU, HeinrichFINOL-URDANETA, RocioBECKER, StefanRAASCH, Walter
    • C07K14/435
    • C07K14/43504C07K14/8114
    • 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; wherein a modulatory effect of the (poly)peptide determined in step (i) that is at least 50% of the modulatory effect of Conkunitzin-S1 indicates that the (poly)peptide re suitable for modulating the activity of said channel having the activity of a Kv1.7 containing channel; and wherein the determination of essentially no modulatory effect in step (ii) indicates that the (poly)peptide is specifically modulating the activity of channels having the activity of a Kv1.7 containing channel.