KR20140123311A - Targeting Peptide for Cancer and Medical Use Thereof - Google Patents

Abstract

The present invention relates to cancer targeting peptide, a cancer diagnosis kit using the same, and a drug delivery composition. According to the present invention, peptide capable of efficiently targeting various cancer tissues can be practically used as a small molecule diagnosis probe capable of diagnosing cancer development or used as a drug delivery material for cancer treatment and cancer prevention.

Description

Cancer targeting peptides and their medical applications {Targeting Peptide for Cancer and Medical Use Thereof}

The present invention relates to a cancer-screening peptide and its use for cancer diagnosis and drug delivery.

Cells, the smallest units that make up the human body, divide by intracellular regulatory functions when normal, and maintain cell balance while growing, dying, and disappearing. When a cell is damaged for some reason, it is treated and regenerated to serve as a normal cell, but if it does not recover, it will die by itself. However, cancer is defined as a condition in which abnormal cells that do not control these proliferation and inhibition for many reasons are not only excessively proliferating but also invade surrounding tissues and organs, resulting in mass formation and normal tissue destruction. Cancer is a cell proliferation that can not be inhibited, and it destroys normal cell and organ structure and function, so its diagnosis and treatment are very important.

On the other hand, a drug delivery system or target treatment selectively delivering a drug to cancer cells and tissues is a technology that has received much attention. This is because the use of the same amount of anticancer agent can increase the efficacy of the drug and at the same time can greatly reduce adverse effects on normal tissues. When applied to gene therapy, the virus can be selectively delivered to cancer cells, thereby increasing treatment efficiency and reducing serious side effects. So far, we have developed antigens that are specific for tumor cells and antibodies that target them. However, in the case of antibodies, there are problems such as concerns of immune response and low efficiency of penetration into tissues. On the other hand, in the case of peptides, it is advantageous that the molecular weight is small so that there is less fear of immune reaction and easy penetration into tissues. Therefore, when a cancer-targeting peptide is linked to a conventional anticancer agent, it can be utilized as an intelligent drug delivery system that selectively transfers a drug to a tumor. Therefore, development of a cancer-targeting peptide is required, and Korean Patent Publication No. 10-01-0132455 Discloses bcl-2 binding peptides of cancer cells, but it is still in- vitro studies.

Therefore, unlike the screening method which has been studied at the existing culture cell level, the present invention provides a novel cancer screening peptide and its medical use through screening in vivo by constructing a mouse model transplanted with actual human cancer cells .

In order to solve the above problems, the present invention provides a cancer-screening peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 20 and a polynucleotide encoding the same do.

The present invention also provides a cancer diagnostic kit comprising a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO:

The present invention also provides a drug delivery composition comprising a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO:

The peptide according to the present invention can be effectively used as a drug delivery material for the treatment and prevention of cancer and a low molecular diagnostic probe capable of diagnosing the expression of cancer by targeting various cancer tissues with excellent efficiency.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph showing a method for constructing an animal model in which various kinds of carcinoma are formed according to Example 1 of the present invention, and the results of the confirmation. FIG.
2 is a plan view of an M13 phage display bio-panning for screening peptides targeting various cancer tissues according to Example 2 of the present invention.
FIG. 3 is an in vivo imaging result obtained by amplifying the 20 loop type peptide expression phage shown in Table 2, measuring the concentration, labeling the Cy5.5 fluorescent probe, and analyzing the target ability.
FIG. 4 is an ex vivo imaging result obtained after completion of the in vivo imaging experiment of the loop-type peptide-expressing phage at the 11th day of the experiment to compare the fluorescence intensities of cancer tissues.
FIG. 5 is a graph showing the distribution of the peptides of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 20 having 20 well peptides in Table 2, ex vivo imaging results.
Fig. 6 shows the in vivo and ex vivo imaging results of the target ability of a phage expressing the five loop type peptide of the present invention having excellent targeting ability in a xenograft model derived from a pancreatic cancer.

The present invention provides a cancer-screening peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO:

The inventors of the present invention have identified peptides (Tumor-targeting peptides) that specifically bind to cancer tissues in human carcinomas through the construction of a mouse model transplanted with actual human cancer cells and screening in vivo , And that the novel peptide can be used as an imaging probe capable of diagnosing cancer site and progression, and furthermore, cancer metastasis, and an effective drug delivery application.

More specifically, the sequence of SEQ ID NO: 1 is AKATCPA, the sequence of SEQ ID NO: 7 is TNANHYF, the sequence of SEQ ID NO: 8 is GWSGLSV, the sequence of SEQ ID NO: 9 is LYANSPF, and the sequence of SEQ ID NO: 20 is IKVGKVQ.

The peptide of the present invention is a low molecular peptide consisting of seven amino acids. Low molecular weight peptides are small in size and stabilized three-dimensionally. They are easy to pass through the mucosa and can recognize molecular targets even in deep tissues. In addition, since the low molecular peptide according to the present invention secures stability through local injection and minimizes immunoreactivity, it has an advantage of early diagnosis of cancer. The low molecular peptide according to the present invention is relatively simple and less toxic than the antibody in the mass production.

In addition, the low molecular peptide according to the present invention has a high binding strength to a target substance rather than an antibody, and does not undergo denaturation during thermal / chemical treatment. Also, because of its small size, it can be used as a fusion protein by attaching it to other proteins. It can be used as a diagnostic kit and a drug delivery material because it can be specifically attached to a polymer protein chain.

The peptides of the present invention can be readily prepared by chemical synthesis known in the art (Creighton, Proteins, Structures and Molecular Principles, W. H. Freeman and Co., NY, 1983). Typical methods include liquid or solid phase synthesis, fractional condensation, F-MOC or T-BOC chemistry (see, for example, Chemical Approaches to the Synthesis of Peptides and Proteins, Williams et al., Eds., CRC Press, Boca Raton Florida A Practical Approach, Atherton & Sheppard, Eds., IRL Press, Oxford, England, 1989).

The peptides of the present invention can also be produced by genetic engineering methods. First, a DNA sequence encoding the peptide is constructed according to a conventional method. DNA sequences can be constructed by PCR amplification using appropriate primers. Alternatively, the DNA sequence may be synthesized by standard methods known in the art, for example, using an automated DNA synthesizer (e.g., marketed by Biosearch or Applied Biosystems). The constructed DNA sequence is operatively linked to the DNA sequence and contains one or more expression control sequences (e.g., promoters, enhancers, etc.) that regulate the expression of the DNA sequence , And the host cells are transformed with the recombinant expression vector formed therefrom. The resulting transformant is cultured under appropriate medium and conditions so that the DNA sequence is expressed, and the substantially pure peptide encoded by the DNA sequence is recovered from the culture. The recovery can be performed using methods known in the art (e.g., chromatography). By "substantially pure peptide" herein is meant that the peptide according to the invention is substantially free of any other proteins derived from the host. Genetic engineering methods for peptide synthesis of the present invention can be found in the following references: Maniatis et al., Molecular Cloning; A laboratory Manual, Cold Spring Harbor Laboratory, 1982; Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, N. Y., Second (1998) and Third (2000) Edition; Gene Expression Technology, Method in Enzymology, Genetics and Molecular Biology, Method in Enzymology, Guthrie & Fink (eds.), Academic Press, San Diego, Calif., 1991; And Hitzeman et al., J. Biol. Chem., 255: 12073-12080,1990.

In order to easily identify, detect and quantify whether the peptide of the present invention binds to cancer tissue, the peptide of the present invention can be provided in a labeled state. That is, they may be provided by linking (e.g., covalently binding or bridging) to a detectable label. The detectable label is a chromogenic enzyme (e.g., peroxidase (peroxidase), alkaline phosphatase (alkaline phosphatase)), radioactive isotopes (for ^{example: 124 I, 125 I, 111} In, 99 mTc, 32 P, 35 S), A chromophore, a luminescent material or a fluorescent material such as FITC, RITC, rhodamine, cyanine, Texas Red, fluorescein, phycoerythrin, Quantum dots), and the like.

Similarly, the detectable label may be an antibody epitope, a substrate, a cofactor, an inhibitor or an affinity ligand. Such labeling may be performed during the synthesis of the peptide of the present invention, or may be performed in addition to the peptide already synthesized. If a fluorescent substance is used as a detectable label, the cancer can be diagnosed by fluorescence-based tomography (FMT). For example, the peptide of the present invention labeled with a fluorescent substance can be circulated into the blood and the fluorescence by the peptide can be observed by fluorescence tomography. If fluorescence is observed, it is diagnosed as cancer.

In one embodiment of the present invention, the cancer may be a solid tumor. More specifically, the cancer-screening peptide according to the present invention may be used for the treatment of brain tumors, low-grade astrocytoma, (CNS), craniopharyngioma, ependymoma, brain stem tumor, head and neck cancer, pancreatic adenoma, meningioma, meningioma, cystic neoplasia, We report a case of a patient with head and neck tumor, larygeal cancer, oopgaryngeal cancer, nasal cavity / PNS tumor, nasopharyngeal tumor, salivary gland tumor, hypopharyngeal cancer Hypopharyngeal cancer, thyroid cancer, oral cavity tumor, chest tumor, small cell lung cancer, non small cell lung cancer, thymoma ), Mediastinal tumors breast cancer, Abdomen-pelvis tumor, Stomach cancer, Hepatoma, Gall bladder cancer, Esophageal cancer, Esophageal cancer, Breast cancer, Male breast cancer, Pancreatic cancer, small intestinal tumor, large intestinal tumor, anal cancer, bladder cancer, renal cancer, pancreatic cancer, pancreatic cancer, male genital cancer, penile cancer, prostate cancer, female genital cancer, cervix cancer, endometrial cancer (including breast cancer), cancer of the uterine cervix Endometrial cancer, ovarian cancer, uterine sarcoma, vaginal cancer, female vaginal cancer, female urethral cancer, or skin cancer. . Even more preferably lung cancer or pancreatic cancer, to be used for its diagnosis and drug delivery.

The present invention also provides a polynucleotide encoding the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: The polynucleotides can be obtained as described above.

The present invention also provides a cancer diagnostic kit comprising a cancer-screening peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: The peptides may be those obtained by chemical or genetic engineering methods as described above. The diagnostic kit of the present invention may further comprise a buffer or reaction solution which stably maintains the structure or physiological activity of the peptide. Further, in order to maintain stability, it may be provided in a powder state or in a state dissolved in an appropriate buffer or maintained at 4 캜.

Herein, the term "diagnosis" in the present invention means to confirm existence or characteristic of a pathological condition. For purposes of the present invention, the diagnosis is to identify the presence or characteristics of the cancer.

The diagnosis of cancer using the peptide of the present invention can be made by detecting the binding of the peptide of the present invention to the tissue or cells directly obtained by blood, urine or biopsy.

Also, in order to facilitate identification, detection and quantification of the peptide of the present invention bound to cancerous tissue, the peptide of the present invention may be provided in a labeled state as described above.

When the peptide of the present invention is provided without labeling, the cancer diagnostic kit of the present invention can be used to search for a cancer-causing part, in particular, And < / RTI > The components may be known compounds for the labeling of the peptides of the invention or may be conjugated to a peptide of the invention or an antibody against a particular receptor that binds to the peptide of the invention or a secondary antibody thereto, And may be a reagent for detection thereof.

In addition, the peptide of the present invention may be provided in a form coated on the surface of a plate. In this case, cancer can be diagnosed by inoculating the subject cancer tissue or cancer cells directly to the plate, reacting under appropriate conditions, and observing the binding of the cancer and the peptide on the surface of the plate.

The present invention also provides a drug delivery composition comprising a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO:

The peptide according to the present invention can be used as an intelligent drug delivery vehicle for selectively delivering a drug to cancer tissues. When the peptide of the present invention is used in combination with a conventionally known drug to treat cancer, the peptide of the present invention selectively transmits the drug only to cancer tissues and cancer cells, thereby increasing the efficacy of the drug, Can significantly reduce the side effects.

The above drug may be used as an anticancer agent, and any anticancer agent that can be linked to the peptide of the present invention is not limited as long as it is conventionally used for the treatment of cancer. Such as cisplatin, 5-fluorouracil, adriamycin, methotrexate, vinblastine, platelets, chlorambucil, cyclophosphamide, melphalan, nitroguanestad, nitroso urea, taxol, paclitaxel, docetaxel, 6 - mercaptopurine, 6-thioguanine, bleomycin, daunorubicin, doxorubicin, epirubicin, dirubicin, mitomycin-C, hydroxyurea and the like. The linkage between the anticancer agent and the peptide of the present invention can be carried out by a method known in the art, for example, through covalent bonding, crosslinking and the like. For this purpose, the peptide of the present invention can be chemically modified to the extent that its activity is not lost if necessary.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> Various people carcinoma  Formative animal model construction

in An animal model for human lung cancer derived cancer was constructed to proceed with vivo peptide screening. To construct the animal model, Balb / c nude mice were used. A549 cells, a human lung cancer cell, were subcultured to measure the number of cells. To construct a heterogeneous xenograft model, A549 cells 5 × 10 ⁵ cells / 50 μl were injected into the right thigh subcutaneous tissues. The cancer tissue size was measured up to about 1 month (4 weeks), and the in vivo peptide screening was carried out when the size of the cancer tissue grew to about 200 mm ³ .

In addition, an animal model was constructed by the same method using human lung cancer cell A549 as well as human pancreatic cancer cell BxPC3.

In order to construct each orthotopic xenograft model, A549 / Fluc cells and BxPC3 / Fluc cells were subcultured and the above cancer cells were injected into the lungs and pancreas of the mice, respectively. Since the above model injected cancer cells directly into mouse organs, D-Luciferin was intraperitoneally injected at intervals of 7 days and the degree of luminescence was measured by IVIS spectral imaging system (Xenogen) The growth saturation of cancer was confirmed by luminescence imaging measurement. Approximately four weeks later, when the emission intensity was found to be about 10 ⁷ photons / s / cm ² / sr, in vivo imaging. The animal model construction process and the imaging result are shown in Fig.

1 is a model construction process of a heterozygous mouse model (A549 cell and BxPC3 cell), B is a mouse model (A549 / Fluc cell) heterozygous for the lung, C is a mouse model of heterozygous transplantation in the pancreas Model (BxPC3 / Fluc cells).

1 (1) is a photograph of the result of cancer tissue formation of a mouse model (A549 cell and BxPC3 cell) in which cancer has been formed four weeks after heterozygous transplantation. Fig. 1 (2) (A549 / Fluc cells), and (3) the imaging results (BxPC3 / Fluc cells) of a mouse model in which the cancer was formed 4 weeks after the xenograft transplantation in the pancreas.

& Lt; Example 2 > M13 Phage Peptide Library in vivo screening - in vivo Phage display

The animal model constructed in Example 1, a human lung cancer-derived xenograft tumor, was constructed to have approximately 2.7 billion different amino acid sequences through a random-loop-type peptide library (a random array consisting of 7 amino acids) in a mouse model formed on the right hind limb Loop type peptide library-PhD ^™ phage display peptide library kit, purchased from New England Biolabs (NEB)), in vivo The screening of the peptides with higher specificity was designed to be selectable. In order to screen for the peptide targeting cancer tissues formed in the constructed mouse model, M13 phage peptide library (approximately 2.7 billion loop amino acid peptide having seven amino acid sequences was inserted into the M13 phage gp3 (a fusion between the biotransformation and the M13 phage peptide library), and a peptide expression phage that can be specifically targeted to the cancer tissue through various washing conditions Respectively. The screening schedule and reaction conditions associated therewith are shown in FIG. 2 and Table 1, respectively.

[Table 1]

Specifically, FIG. 2 is a plan view of M13 phage screening for peptide screening targeted to cancer tissues, which comprises (1) constructing a mouse model in which cancer tissue is formed on the right hind limb, and (2) After the phage library expressing the constructed loop type peptide library was injected through the tail vein and circulated, (3) it was washed under various conditions, and (4) finally the targeted phage was eluted to obtain a phage. The above-obtained phage was infected with E. coli, amplified, circulated through a mouse tail vein and circulated, and then repeated at higher intensity washing conditions, thereby repeating the process of finding a more specific and strongly binding phage (This is called biopanning). Table 1 is a table showing the four-step bio-panning washing conditions for detecting phages expressing peptides having high targeting ability and specificity in cancer tissues in the in vivo circulation process. And then subjected to biofanning four times each to obtain a phage having a peptide that targets the cancer tissue formed in vivo. The resulting phage was infected with E. coli ER2738 cells, which were host cells, and amplified on LB medium. Then, about 100 phage plaques were randomly selected to separate and purify M13 phage genomic DNA (single stranded circular DNA) The sequence was identified and the amino acid sequence of the peptide moiety that was expressed on the phage surface protein (gp3 minor coat protein) and targeted to the cancer tissue was identified. The results are shown in Table 2 below. Table 2 shows a total of 20 amino acid sequences (SEQ ID NO: 1 to SEQ ID NO: 20) through the Clustal X sequence analysis program, and five distinct sequences were selected from the sequences.

[Table 2]

< Example  3> in vivo  Formed on In cancer tissue Target Peptides  Fluorescent label ring

in To confirm the specific peptide targeting the cancer tissue obtained from the vivo screening, the phage expressing each loop type peptide was amplified and then titering was performed to determine the concentration of the phage solution. The phage expressing each of the loop-type peptides obtained in the above was in In order to confirm the efficiency of specifically targeting cancer tissue in vivo through vivo imaging, a step of attaching a Cy5.5 fluorescent probe was carried out.

Specifically, 1 μg / μl of N-hydroxysuccinimide esters of Cy5.5 (Amersham) was added to ^10-12 plaque forming units (pfu) of phage concentration in 1 mL bicarbonate buffer (pH 8.3) The Cy5.5 fluorescent probe was connected to the phage surface. The phage expressing each of the loop type peptides connected to the Cy5.5 fluorescent probe was obtained by precipitation with 200 mu l of a 20% (w / v) PEG 8000 / 2.5 M NaCl solution. To determine the proportion of Cy5.5 fluorescent blobs connected to each final phage sample, the ratio was determined using the IVIS spectral imaging system (Xenogen) and the ROI value was determined using the instrument software program . Specifically, comparing the phage samples that were ligated to each other in terms of the concentration of the added Cy5.5 fluorescence probe, the fluorescence coupling ratio of each of the processed phage samples was almost the same And it was confirmed that they were uniformly connected without.

< Example  4> Loop type The peptide  Expressed Phage  real Cancer tissue Targeting  Whether for confirmation in vivo Imaging

The phage expressing the respective loop type peptides obtained in Example 3 were injected into the xenograft mouse model of lung cancer derived from the same mouse model constructed in Example 1 through the tail vein, and the images were measured at intervals of one day, In the circulation pathway of peptides and other organs and tissues. Thus, it has been confirmed that complete targeting of cancer tissues is achieved.

The peptide sequences of five groups out of a total of 20 peptide sequences identified through the bio-panning process in Example 2 were in (Fig. 3, G1, G7, G8, G9, and G20), indicating excellent targeting ability in vivo imaging.

Furthermore, in order to ex vivo examine which part of the cancer tissue the phage expressing each of the loop-type peptides targets, only the cancer tissue is isolated and the whole cancer tissue itself and the cancer tissue are sectioned into several fragments The results are shown in Fig. 4 and Fig.

Specifically, as shown in FIG. 3, FIG. 4, and FIG. 5, when Cy5.5 before processing and empty phage without peptide expression were compared, the peptide sequences of 20 groups in Table 2, The five sequences of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 20 were selected according to excellent targeting ability, and the five sequence peptides were targeted to the outside of cancer tissue, It was confirmed that the five peptide sequences specifically target cancer tissues accurately according to the results of fluorescence measurement.

Then, based on the results of FIG. 3, FIG. 4 and FIG. 5, in order to more accurately compare the target efficiencies, the collected cancer tissues were collected, and only the targeted phage was eluted, and the respective phage concentrations were measured by titering. Since the size and the weight of the cancer tissue are different, the weight of each cancer tissue was measured, and the amount of the confirmed phage was calculated based on the cancer tissue weight. Also, in order to more accurately quantify each imaging result, in vivo And ex vivo Imaging was performed by measuring the region of interest (ROI) of the IVIS spectrum (Xenogen). The results are shown in Table 3 below. Referring to Table 3, it can be confirmed that the five peptide sequences have excellent targeting ability when compared with the Cy5.5 and the empty phage as reference.

[Table 3]

Also, in the xenograft model derived from pancreatic cancer among the mouse models constructed in Example 1, the process was performed under the same conditions as those described above, and the results are shown in FIG. As can be seen in Fig. 6, the phage expressing each loop-type peptide showed excellent targeting ability in human lung cancer as well as pancreatic cancer tissue. The above results indicate that the peptide sequence can be targeted not only to a specific cancer but also to a variety of cancer tissues and it is also possible to utilize the imaging system using the peptide of the present invention Suggesting that it can be diagnosed.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

<110> University of Ulsan Foundation for Industry Cooperation <120> Targeting Peptide for Cancer and Medical Use Thereof <130> ADP-2013-0098 <160> 20 <170> Kopatentin 2.0 <210> 1 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 1 targeting cancer cell <400> 1 Ala Lys Ala Thr Cys Pro Ala   1 5 <210> 2 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 2 targeting cancer cell <400> 2 Ser Trp Gln Ile Gly Gly Asn   1 5 <210> 3 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 3 targeting cancer cell <400> 3 Thr Val Arg Thr Ser Ala Asp   1 5 <210> 4 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 4 targeting cancer cell <400> 4 Ile Gly Asn Ser Asn Thr Leu   1 5 <210> 5 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 5 targeting cancer cell <400> 5 Ile Lys Val Gly Lys Leu Gln   1 5 <210> 6 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 6 targeting cancer cell <400> 6 Asn Trp Gly Asp Arg Ile Leu   1 5 <210> 7 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 7 targeting cancer cell <400> 7 Thr Asn Ala Asn His Tyr Phe   1 5 <210> 8 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 8 targeting cancer cell <400> 8 Gly Trp Ser Gly Leu Ser Val   1 5 <210> 9 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 9 targeting cancer cell <400> 9 Leu Tyr Ala Asn Ser Pro Phe   1 5 <210> 10 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 10 targeting cancer cell <400> 10 Ser Ile Ser Ser Leu Thr Asp   1 5 <210> 11 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 11 targeting cancer cell <400> 11 Asn Trp Gly Asp Arg Ile Arg   1 5 <210> 12 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 12 targeting cancer cell <400> 12 Asn Trp Gly Asp Arg Ile Glu   1 5 <210> 13 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 13 targeting cancer cell <400> 13 Arg Ser Ala Asn Ile Phe Thr   1 5 <210> 14 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 14 targeting cancer cell <400> 14 Phe Asn Met Phe Ser Arg Phe   1 5 <210> 15 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 15 targeting cancer cell <400> 15 Ile Ser Ala Trp Pro Thr Arg   1 5 <210> 16 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 16 targeting cancer cell <400> 16 Ser Ile Ser Ser Leu Thr His   1 5 <210> 17 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 17 targeting cancer cell <400> 17 Phe Leu Asn Pro Thr Thr Thr   1 5 <210> 18 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 18 targeting cancer cell <400> 18 Lys Asn Leu Thr Arg Leu Ala   1 5 <210> 19 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 19 targeting cancer cell <400> 19 Met Ala Arg Tyr Met Ser Ala   1 5 <210> 20 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> peptide 20 targeting cancer cell <400> 20 Ile Lys Val Gly Lys Val Gln   1 5

Claims (8)

SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 20. A polynucleotide encoding the amino acid sequence of claim 1. A kit for cancer diagnosis comprising a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: The method of claim 3,
Wherein the peptide is labeled with one selected from the group consisting of a chromogenic enzyme, a radioisotope, a chromopore, a luminescent material, and a fluorescent material. The method of claim 3,
Wherein the diagnosis is carried out by reacting the peptide with the tissue or cells directly obtained by blood, urine or biopsy to detect their binding. A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 20. The method according to claim 6,
Wherein the composition is specific for cancer. The method according to claim 6,
Wherein the drug is an anticancer agent.

Images