Peptide having cancer selective translocation function and use thereof

a technology of selective translocation and peptide, which is applied in the direction of peptide/protein ingredients, peptide sources, instruments, etc., can solve and achieve the effect of reducing the problems of side effects and low image quality

Inactive Publication Date: 2015-06-18
SEOUL NAT UNIV R&DB FOUND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]It is an object of the present invention to provide a peptide which can minimize problems associated with side effects or low image quality, which can occur due to the non-specific distribution of conventional tumor diagnostic or therapeutic agents, in which the peptide can deliver tumor diagnostic agents or disease therapeutic agents selectively to target cells only.
[0009]Accordingly, a main object of the present invention is to reconstitute the oxidation / reduction balance in mutant strains, which lack each of 472 genes involved in breathing, electron transfer and oxidation / reduction reactions, at the genome-wide level by anaerobic fermentation, and based on the reconstitution, select genes capable of controlling the carbon metabolic flow and provide a mutant microorganism in which lactic acid, succinic acid or ethanol is produced in large amounts but the production of other organic acids is significantly reduced, and a method for producing the mutant microorganism. Still another object of the present invention is to use the peptide for the diagnosis or treatment of cancer.

Problems solved by technology

However, if materials that are used for the diagnosis and treatment of diseases do not act specifically against such targets only, problems of side effects and low image quality will be caused by non-specific distribution of the materials.

Method used

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  • Peptide having cancer selective translocation function and use thereof
  • Peptide having cancer selective translocation function and use thereof
  • Peptide having cancer selective translocation function and use thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Target-Selective Cell / Tissue-Penetrating Peptide

[0040]Peptides were prepared by the F-moc chemistry method using an automatic peptide synthesizer, and then the peptide moieties were cut by resin, washed, freeze-dried, followed by purification by liquid chromatography, thereby preparing a VPTD peptide represented as SEQ ID NO: 1 (VSRRRRRRGGRRRR) and an HPTD peptide represented as SEQ ID NO: 2 (CSSRKKNPNCRRH). The molecular weights of the purified peptides were analyzed by MALDI.

example 2

Preparation of Tumor-Targeting and Tumor-Penetrating Peptide-Drug Conjugates

[0041]The VPTD peptide of SEQ ID NO: 1 and the HPTD peptide of SEQ ID NO: 2, prepared in Example 1, contained the free-sulfhydryl group of a cysteine residue, and thus chemical linkage between the peptide and the anticancer protein RNase or doxorubicin was induced using the free-sulfhydryl group as a chemical crosslinking agent. The surfaces of RNase and doxorubicin (Dox) were modified to have a thiol group attached to the carboxyl group on the surfaces. 10 molecules of peptide-SH were added to 1 molecule of particle surface-SH and reacted at 4° C. for 12 hours, and then unreacted molecules were removed by ultrafiltration, followed by freeze drying, thereby obtaining a conjugate of the VPTD peptide of SEQ ID NO: 1 and RNase, a conjugate of the VPTD peptide of SEQ ID NO: 1 and Dox, a conjugate of the HPTD peptide of SEQ ID NO: 2 and RNase, and a conjugate of the HPTD peptide of SEQ ID NO: 2 and Dox.

example 3

Tumor Cell Penetration Abilities of Tumor-Targeting and Cell-Penetrating Peptides

[0042]In order to test the tumor cell-targeting and tumor cell-penetrating abilities of the VPTD peptide of SEQ ID NO: 1 and the HPTD peptide of SEQ ID NO: 1, prepared in Example 1, the termini of the prepared peptides were labeled with a fluorescent dye, and then each of the peptides was inoculated into a tumor cell line (MDA-MB-231, ATCC) at various concentrations.

[0043]60 minutes after the inoculation, the fluorescence of the cells was measured by FACS, and the results of the measurement are shown in FIG. 1. As can be seen in FIG. 1(A), the fluorescence of the tumor cells increased in a manner dependent on the concentration of the peptide. FIG. 1(B) shows the results of observing the fluorescence of the tumor cells by a confocal laser scanning microscope in order to examine the tumor cell penetration abilities of the VPTD peptide of SEQ ID NO: 1 and the HPTD peptide of SEQ ID NO: 1. In FIG. 1(B), in ...

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Abstract

The present invention relates a peptide having cancer selective translocation function, and the use thereof, and more particularly to a VEGF-binding protein transduction domain (VPTD) represented as SEQ ID NO: 1 or a heparin-binding protein transduction domain (HPTD) represented as SEQ ID NO: 2, which bind specifically to VEGF and heparin, which are overexpressed specifically in tumor cells or tumor tissues, and to a conjugate comprising a drug linked to the peptide.The peptide and the peptide-drug conjugate bind specifically to VEGF and heparin in tumor cells or tumor tissue and accumulate in the tumor cells or tumor tissue, and thus can be used for the accurate diagnosis and treatment of cancer. Also, the non-specific distribution of the peptide or the conjugate in the body after administration is inhibited, and thus the side effects thereof can be minimized. Accordingly, the peptide or the conjugate is useful for the diagnosis and treatment of cancer.

Description

TECHNICAL FIELD[0001]The present invention relates to a peptide having cancer selective translocation function, and the use thereof, and more particularly to a peptide having cancer selective translocation function, a conjugate comprising a drug such as an anticancer agent linked to the peptide having cancer selective translocation function, and the use thereof.[0002]The peptide having cancer selective translocation function of the present invention or a conjugate of the peptide and a drug can selectively penetrate tumor cells or tumor tissues, and thus can be widely used for the diagnosis or treatment of various cancers.BACKGROUND ART[0003]For the treatment of tumors or the diagnosis and treatment of inflammations, for example, osteoarthritis, and skin diseases, many studies have been conducted on proteins or small materials, which are present specifically in disease foci. Thus, many kinds of such materials have been identified while studies on treatment with such materials have al...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/48A61K49/00A61K31/704C07K7/08A61K38/46
CPCA61K47/48246C07K7/08A61K49/0056A61K31/704A61K38/465A61K38/00A61K47/64A61P35/00C07K14/47C07K2319/10C12Q1/26C12Q1/58C12Q1/66C12Y301/13G01N33/574A61K47/50A61K49/14C07K14/435
Inventor PARK, YOON JEONGCHUNG, CHONG-PYOUNGSUH, JIN SOOKCHOI, YOON JUNG
Owner SEOUL NAT UNIV R&DB FOUND
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