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。
摘要:
The invention relates to relatively short peptides (termed Conopeptide-Y family peptides or CPY family peptides or CPY peptides herein), about 30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which are rich in the amino acid tyrosine.
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:
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:
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:
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。