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1. 发明申请

WO2013003178A1 SULFATION OF WNT PATHWAY PROTEINS 审中-公开
标题翻译： WNT途径蛋白的硫化
公开(公告)号：WO2013003178A1
公开(公告)日：2013-01-03
申请号：PCT/US2012/043451
申请日：2012-06-21
申请人： ENZO BIOCHEM, INC. , RABBANI, Joshua , DONEGAN, James J. , LI, Xiaofeng
发明人： RABBANI, Joshua , DONEGAN, James J. , LI, Xiaofeng
IPC分类号： C07K14/51 , C07K7/04
CPC分类号： A61K38/1709 , A61K38/08 , A61K38/10 , C07K14/47 , C07K14/51 , C07K14/705 , C07K14/71
摘要： Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner. Additionally provided is a method of enhancing a Wnt signaling pathway comprising contacting an LRP5/6 receptor in the Wnt signaling pathway with either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, in a manner sufficient to enhance the Wnt signaling pathway. Further provided is a method of treating a subject having a disease exacerbated by inhibition of a Wnt signaling pathway comprising administering either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, to the subject in a manner sufficient to reduce the inhibition of the Wnt signaling pathway. Also, a method of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner is provided. The method comprises adding the above-described composition that is capable of inhibiting binding of a protein ligand to its binding partner to the protein ligand and its binding partner in a manner sufficient to inhibit binding of the protein ligand to its binding partner.
摘要翻译：提供了包含包含氨基酸和/或氨基酸类似物的肽的组合物，其包含包含Tyr43或Tyr213的硬化蛋白片段的连续序列。还提供了包含包含少于约75个氨基酸和/或氨基酸类似物的肽的组合物，其包含能够被硫酸化的氨基酸或氨基酸类似物，其中该组合物能够抑制与LRP结合的硬皮蛋白。还提供了一种组合物，其包含包含小于约75个氨基酸和/或氨基酸类似物的肽，其包含能够翻译后硫酸化的氨基酸或氨基酸类似物，其中组合物能够抑制蛋白质配体的结合，所述蛋白质配体包含硫酸化位点到其结合配偶体。另外提供了增强Wnt信号传导途径的方法，包括使Wnt信号传导途径中的LRP5 / 6受体与包含硬化蛋白片段序列的任一上述组合物接触或能够抑制硬化蛋白酶与LRP结合，其中酪氨酸或酪氨酸类似物不被硫酸化，以足以增强Wnt信号通路的方式。还提供了一种治疗具有通过抑制Wnt信号传导途径加重疾病的受试者的方法，包括施用包含硬化蛋白酶片段序列的上述组合物或能够抑制硬化蛋白与LRP的结合，其中酪氨酸或酪氨酸类似物不以足以降低Wnt信号传导途径抑制的方式硫酸化。此外，提供了抑制包含硫酸化位点的蛋白质配体与其结合配偶体的结合的方法。该方法包括加入能够以足以抑制蛋白质配体与其结合配偶体的结合的方式将蛋白质配体与其结合配偶体结合至蛋白质配体及其结合配偶体的上述组合物。

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