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。

公开(公告)号：US20050137132A1

公开(公告)日：2005-06-23

申请号：US10892499

申请日：2004-07-16

申请人： Baldomero Olivera ,  Maren Watkins ,  Heinrich Terlau ,  Michael Ferber

发明人： Baldomero Olivera ,  Maren Watkins ,  Heinrich Terlau ,  Michael Ferber

IPC分类号： A61K38/17

CPC分类号： A61K38/17

摘要： The present invention is directed to kappaM (κM) conopeptide RIIIK and its use for blocking the flow of potassium ions through voltage-gated potassium channels. The κM conopeptides include unglycosylated and O-glycosylated peptides.

摘要翻译： 本发明涉及kappaM（kappaM）肽肽RIIIK及其通过电压门控钾通道阻断钾离子流的用途。 卡帕霉素肽包括非糖基化和O-糖基化肽。

公开(公告)号：US20060178303A1

公开(公告)日：2006-08-10

申请号：US11222216

申请日：2005-09-09

申请人： Baldomero Olivera ,  Heinrich Terlau ,  Julita Imperial ,  James Garrett

发明人： Baldomero Olivera ,  Heinrich Terlau ,  Julita Imperial ,  James Garrett

IPC分类号： A61K38/16 ,  C07K14/435

CPC分类号： C07K14/43504 ,  A61K38/00

摘要： The present invention is directed to conopeptides termed conkunitzins and their use for blocking the flow of potassium ions through voltage-gated potassium channels. In view of the Kunitz domain in the conkunitzins, they are also useful for inhibiting platelet aggregation and as protease inhibitors.

摘要翻译： 本发明涉及称为康尼他嗪的肽，以及它们用于阻断钾离子通过电压门控钾通道流动的用途。 鉴于康un嗪中的Kunitz结构域，它们也可用于抑制血小板聚集和蛋白酶抑制剂。

公开(公告)号：US5672682A

公开(公告)日：1997-09-30

申请号：US619936

申请日：1996-03-18

申请人： Heinrich Terlau ,  Ki-Joon Shon ,  Michelle Grilley ,  Baldomero M. Olivera

发明人： Heinrich Terlau ,  Ki-Joon Shon ,  Michelle Grilley ,  Baldomero M. Olivera

IPC分类号： A61K38/00 ,  C07K14/435 ,  C07K14/00

CPC分类号： C07K14/43504 ,  A61K38/00

摘要： A new peptide, .kappa.-conotoxin PVIIA, is disclosed. This peptide is found naturally in the cone snail Conus purpurascens and has the amino acid sequence Cys-Arg-Ile-Xaa-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val (SEQ ID NO:1) where Xaa represents 4-trans-hydroxyproline hydroxyproline or proline. This peptide together with a previously disclosed peptide, .delta.-conotoxin PVIA, act synergistically to rapidly immobilize fish which are injected with the two peptides. Injection of .kappa.-conotoxin PVIIA alone results in different symptoms with an injected fish becoming hyperactive and then contracting and suddenly extending all major fins. This "fin-popping" occurs repeatedly resulting in a series of jerky movements, but injection of only .kappa.-conotoxin PVIIA does not immobilize or kill the fish.

摘要翻译： 公开了一种新的肽，κ-毒素PVIIA。 这种肽天然存在于锥螺旋锥体中，具有氨基酸序列Cys-Arg-Ile-Xaa-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-Cys-Ser -Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val（SEQ ID NO：1），其中Xaa表示4-反式 - 羟脯氨酸羟脯氨酸或脯氨酸。 该肽与先前公开的肽δ-毒素PVIA一起协同作用以快速固定注射了两种肽的鱼。 单独注射κ-毒素PVIIA导致不同的症状，注射的鱼变得活跃，然后收缩并突然延伸所有主要鳍。 这种“昙花一现”反复发生，导致一连串的剧烈运动，但只注射κ-毒素PVIIA不会使鱼类不能固定或杀死。