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Compositions and methods for treating conditions related to EPHRIN signaling with cupredoxins

A composition, copper-oxygen technology, which is applied in the preparation methods of peptides, chemical instruments and methods, preparations for in vivo tests, etc., can solve the problems of threatening non-cancer cells and so on

Inactive Publication Date: 2008-06-11
THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, these treatments threaten non-cancerous cells, which is stressful to the body and produces many side effects

Method used

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  • Compositions and methods for treating conditions related to EPHRIN signaling with cupredoxins
  • Compositions and methods for treating conditions related to EPHRIN signaling with cupredoxins
  • Compositions and methods for treating conditions related to EPHRIN signaling with cupredoxins

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Experimental program
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Embodiment 8

[0103] The inventors have also found that cupredoxin, which has a similar structure to the loop region of Ephrin G-H, inhibits the growth of mammalian cancer cells in vitro. In summary, plastocyanin from Phormidiumlaminosum, Rusticyanin from Thiobacillus ferrooxidans, and Pseudomonas azurinin all inhibited Mel-2 human melanoma cells and MCF-7 human breast cancer cells in the trypan blue assay. Growth in vitro. See Example 4. In addition, it is now known that the 88-113 residue region of azurin can inhibit the cell growth of MCF-7 breast cancer cells. See Example 10. Finally, it is now known that the 18-mer azurin peptide and the 15-mer pore Ulva plastocyanin peptide corresponding to the structurally similar region of the EphrinB2 GH loop region can inhibit MCF-7 human breast cancer cells, CCF in vitro -Growth of STTG1 brain tumor astrocytoma cells and LN-229 glioblastoma. See Examples 3 and 9.

Embodiment 3 and 9

[0104] Surprisingly, cupredoxin, which is similar in structure to the G-H loop of EphrinB2, can also affect Ephrin-related development in the body. It is now known from the in vivo study of the Ephrin-related development of C. elegans that the cupredoxin Rusticyanin interferes with the formation of tail muscles, while the cupredoxin azurrin prevents embryonic development, both of which are Ephrin related development. See Example 1.

Embodiment 1

[0105] It is now understood that in addition to azurin, the cupredoxin Rusticyanin and plastocyanin also share structural homology with the G and H regions of EphrinB2. See Examples 2 and 5. In addition, it is known that azurin, Phytocyanin and cucumber basic protein share significant structural homology with Ephrin. Because of the general structural conservation in the cupredoxin protein family, it is expected that many other cupredoxins and cupredoxin-like proteins will also show significant structural homology with Ephrin. See Example 2. Therefore, it is proposed that using the composition and method of the present invention, cupredoxin family proteins can generally be used to treat Ephrin signaling-related diseases and cancers. Related special cupredoxins include, but are not limited to, azurin, Rusticyanin, plastocyanin, anacyanin, auracyanin, pseudoazurin, and cucumber basic protein. Exemplary protein sequences here are plastocyanin (SEQ ID NO: 2 and 22), Rusticyanin (SEQ ID...

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Abstract

The present invention relates to compositions and methods of use of cupredoxins, and variants, derivatives and structural equivalents of cupredoxins that interfere with the ephrin signaling system in mammalian cells. Specifically, the invention relates to compositions and methods that use cupredoxins, such as azurin, rusticyanin and plastocyanin, and variants, derivatives and structural equivalents thereof, to treat cancer in mammals.

Description

[0001] Related application [0002] According to USC Sections 119 and 120, this application requires the US provisional patent application 60 / 764,749 filed on February 3, 2006, the US provisional patent application 60 / 682,812 filed on May 20, 2005, and October 6, 2005 The priority of the filed U.S. Patent Application 11 / 244,105, 11 / 244,105 claims the priority of the U.S. Provisional Patent Application 60 / 616,782 filed on October 7, 2004 and the U.S. Provisional Patent Application 60 / 680,500 filed on May 13, 2005 , And is a partial continuation application of U.S. Patent Application 10 / 720,603 filed on November 11, 2003. 10 / 720,603 claims the priority of U.S. Provisional Patent Application 60 / 414,550 filed on August 15, 2003, and it is January 2002 Part of the U.S. Patent Application 10 / 047,710 filed on February 15th is a continuation application, and 10 / 047,710 claims the priority of the U.S. Provisional Patent Application 60 / 269,133 filed on February 15, 2001. The entire contents o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/02A61K39/10A61K39/38A61K39/095A61K39/108A61K49/00C07K1/00C07H21/02C07H21/04
Inventor A·查克拉巴迪T·达斯古普塔山田亨A·乔杜里A·菲亚略朱永华
Owner THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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