JP6841404B2 - peptide - Google Patents
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- JP6841404B2 JP6841404B2 JP2016163465A JP2016163465A JP6841404B2 JP 6841404 B2 JP6841404 B2 JP 6841404B2 JP 2016163465 A JP2016163465 A JP 2016163465A JP 2016163465 A JP2016163465 A JP 2016163465A JP 6841404 B2 JP6841404 B2 JP 6841404B2
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- peptide
- colorectal cancer
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- inflammatory bowel
- bowel disease
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 37
- 206010009944 Colon cancer Diseases 0.000 claims description 22
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 19
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 16
- 229940124597 therapeutic agent Drugs 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 7
- 230000000069 prophylactic effect Effects 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000012830 cancer therapeutic Substances 0.000 claims description 2
- 238000011282 treatment Methods 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 8
- 210000002429 large intestine Anatomy 0.000 description 8
- 230000029663 wound healing Effects 0.000 description 7
- 108700020483 Wnt-5a Proteins 0.000 description 6
- 101150109862 WNT-5A gene Proteins 0.000 description 5
- 102000043366 Wnt-5a Human genes 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 206010009900 Colitis ulcerative Diseases 0.000 description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 101100264057 Mus musculus Wnt5a gene Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 210000004922 colonic epithelial cell Anatomy 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940125700 inflammatory bowel disease agent Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
本発明は、ペプチドに関する。また、本発明は、炎症性腸疾患の予防又は治療剤、大腸がんの治療剤に関する。 The present invention relates to peptides. The present invention also relates to a prophylactic or therapeutic agent for inflammatory bowel disease and a therapeutic agent for colorectal cancer.
潰瘍性大腸炎やクローン病を代表とする炎症性腸疾患（Inflammatory bowel disease：以下IBD）は原因不明の慢性再燃性消化管炎症疾患である。近年、IBDの病態における免疫機構や腸内細菌の関与などが明らかとなっており、それらを標的とする様々な治療が提唱されている。その治療効果の目標は臨床的寛解ではなく、内視鏡的に確認する「粘膜治癒」が重要であり粘膜治癒が得られれば、臨床的寛解の維持、手術率の低下につながることが示されている。IBDに対しては近年多くの治療薬が臨床応用されており、治療成績も向上しているが、同時に治療抵抗性で手術を余儀なくされる症例も依然として多く存在している。また、炎症性腸疾患の患者数は年々増加の一途をたどっており、内科治療に抵抗性で手術にいたる症例も増加している。したがって、既存の内科治療に加え、粘膜治癒を促すことによる長期寛解維持効果を発揮する治療の開発が急務である。 Inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn's disease, is a chronic relapsed gastrointestinal inflammatory disease of unknown cause. In recent years, the immune system and the involvement of intestinal bacteria in the pathophysiology of IBD have been clarified, and various treatments targeting them have been proposed. It has been shown that the goal of the therapeutic effect is not clinical remission, but endoscopically confirmed "mucosal healing" is important, and if mucosal healing is obtained, it will lead to maintenance of clinical remission and reduction of surgical rate. ing. In recent years, many therapeutic agents have been clinically applied to IBD, and the treatment results have improved, but at the same time, there are still many cases in which surgery is unavoidable due to treatment resistance. In addition, the number of patients with inflammatory bowel disease is steadily increasing year by year, and the number of patients who are resistant to medical treatment and undergo surgery is also increasing. Therefore, in addition to the existing medical treatments, there is an urgent need to develop a treatment that exerts a long-term remission maintenance effect by promoting mucosal healing.
一方、進行した大腸癌に対しては分子標的薬の開発などで治療効果は向上しているが、いまだに死亡率は増加傾向にある。進行大腸癌に対する内科治療は、複数の治療を繰り返して実施する過程で治療抵抗性を示し、治療の継続が不可能になってしまう。したがって、既存の抗癌剤治療に加え、別のメカニズムによる大腸癌化学療法の開発が急務である。 On the other hand, for advanced colorectal cancer, the therapeutic effect has been improved by the development of molecular-targeted drugs, but the mortality rate is still on the rise. Medical treatment for advanced colorectal cancer shows resistance to treatment in the process of repeatedly performing a plurality of treatments, making it impossible to continue the treatment. Therefore, there is an urgent need to develop colorectal cancer chemotherapy by another mechanism in addition to the existing anticancer drug treatment.
本発明は、炎症性腸疾患、大腸がんの治療薬を提供することを目的とする。 An object of the present invention is to provide a therapeutic agent for inflammatory bowel disease and colorectal cancer.
本発明者は、Wnt5aの部分ペプチドが炎症性腸疾患、大腸がんに有効であることを見出した。 The present inventor has found that a partial peptide of Wnt5a is effective for inflammatory bowel disease and colorectal cancer.
本発明は、以下のペプチド、炎症性腸疾患の予防又は治療剤、大腸がん治療剤を提供するものである。
項１． 下記のアミノ酸配列（Ｉ）
QLADFRKVGDALKEKYDSAAAMR （Ｉ）
を含む、ペプチド。
項２． 下記のアミノ酸配列（Ｉａ）
R１−QLADFRKVGDALKEKYDSAAAMR （Ｉａ）
（式中、R１は下記の１３種
GVSGSCSLKTCWL、
VSGSCSLKTCWL、
SGSCSLKTCWL、
GSCSLKTCWL、
SCSLKTCWL、
CSLKTCWL、
SLKTCWL、
LKTCWL、
KTCWL、
TCWL、
CWL、
WL、又は
L
のいずれかである）
を含む、項１に記載のペプチド。
項３． GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMRで表される、項１又は２に記載のペプチド
項４． 項１，２又は３のペプチドを有効成分として含む炎症性腸疾患の予防又は治療剤。
項５． 項１，２又は３のペプチドを有効成分として含む大腸がん治療剤。
The present invention provides the following peptides, prophylactic or therapeutic agents for inflammatory bowel disease, and therapeutic agents for colorectal cancer.
Item 1. The following amino acid sequence (I)
QLADFRKVGDALKEKYDSAAAMR (I)
Including peptides.
Item 2. The following amino acid sequence (Ia)
R 1- QLADFRKVGDALKEKYDSAAAMR (Ia)
(In the formula, R 1 is the following 13 types
GVSGSCSLKTCWL,
VSGSCSLKTCWL,
SGSCSLKTCWL,
GSCSLKTCWL,
SCSLKTCWL,
CSLKTCWL,
SLKTCWL,
LKTCWL,
KTCWL,
TCWL,
CWL,
WL or
L
Is one of)
Item 2. The peptide according to Item 1.
Item 3. Item 4. Peptide item 1 or 2 represented by GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMR. A prophylactic or therapeutic agent for inflammatory bowel disease containing the peptides of Items 1, 2 or 3 as an active ingredient.
Item 5. A therapeutic agent for colorectal cancer containing the peptides of Items 1, 2 or 3 as an active ingredient.
本発明のペプチドは、大腸粘膜細胞の増殖を促進し、大腸粘膜の創傷治癒に有効であり、炎症性腸疾患の予防又は治療剤として有用である。 The peptide of the present invention promotes the proliferation of large intestine mucosal cells, is effective for wound healing of the large intestine mucosa, and is useful as a preventive or therapeutic agent for inflammatory bowel disease.
また、本発明のペプチドは、大腸がん細胞の増殖を抑制し、大腸がんの治療剤として有用である。 In addition, the peptide of the present invention suppresses the growth of colorectal cancer cells and is useful as a therapeutic agent for colorectal cancer.
大腸がんの発症は、炎症性腸疾患により促進すると言われており、本発明のペプチドは、潰瘍性大腸炎の治癒促進により、大腸がんを予防でき、かつ大腸がんの治療効果を有し、強力な大腸保護作用を有する。 It is said that the onset of colorectal cancer is promoted by inflammatory bowel disease, and the peptide of the present invention can prevent colorectal cancer by promoting the healing of ulcerative colitis and has a therapeutic effect on colorectal cancer. It has a strong large intestine protective effect.
本発明のペプチドは、大腸粘膜細胞の増殖を促進し、かつ、大腸がんの増殖を抑制するという、相反する作用を併せ持つという格別の効果を奏するものである。 The peptide of the present invention has a special effect of promoting the growth of colon mucosal cells and suppressing the growth of colon cancer, which have contradictory actions.
本発明のペプチドは、ヒトWnt5a由来であり、23アミノ酸のペプチド（I）を必須配列として含み、さらにN末端側にＲ基で表される1〜13個のアミノ酸もしくはペプチドを連結したものであってもよい。これらの23〜36個のアミノ酸からなるペプチドは、共通して式（Ｉ）の23個のアミノ酸配列を保有している。 The peptide of the present invention is derived from human Wnt5a, contains a peptide (I) of 23 amino acids as an essential sequence, and further has 1 to 13 amino acids or peptides represented by R groups linked to the N-terminal side. You may. These peptides consisting of 23 to 36 amino acids commonly carry the 23 amino acid sequences of formula (I).
23個と36個のアミノ酸配列の配列番号は、以下の通りである。
配列番号１： QLADFRKVGDALKEKYDSAAAMR
配列番号２： GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMR
ヒト及びマウスのWnt5aの塩基配列及びアミノ酸配列は公知であり、データベースに下記のアクセッション番号で登録されている。
マウスのWnt5a ： NM_009524
ヒトのWnt5a ： NM_003392
ヒトとマウスのWnt5aの配列番号１，２に対応するアミノ酸配列は同一であり、本発明のペプチドは、ヒト及びマウスを含む哺乳動物に対し、炎症性腸疾患の予防又は治療剤、並びに、大腸がん治療剤として有用である。
The SEQ ID NOs of the 23 and 36 amino acid sequences are as follows.
SEQ ID NO: 1: QLADFRKVGDALKEKYDSAAAMR
SEQ ID NO: 2: GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMR
The nucleotide and amino acid sequences of human and mouse Wnt5a are known and are registered in the database with the following accession numbers.
Mouse Wnt5a: NM_009524
Human Wnt5a: NM_003392
The amino acid sequences corresponding to SEQ ID NOs: 1 and 2 of Wnt5a in humans and mice are the same, and the peptides of the present invention can be used as a prophylactic or therapeutic agent for inflammatory bowel disease in mammals including humans and mice, and the large intestine. It is useful as a cancer therapeutic agent.
配列番号１で示される23アミノ酸のペプチド（I）（QLADFRKVGDALKEKYDSAAAMR）は、エピトープを含んでおり、腸粘膜創傷治癒作用及び大腸がんの増殖抑制作用に必須の部分である。また、本発明のペプチドは水溶性である。 The 23-amino acid peptide (I) (QLADFRKVGDALKEKYDSAAAMR) shown in SEQ ID NO: 1 contains an epitope and is an essential part for intestinal mucosal wound healing action and colon cancer growth inhibitory action. Moreover, the peptide of the present invention is water-soluble.
本発明の式（I）又は(Ia)のペプチドは、固相合成により製造してもよく、これらのペプチドをコードするDNAを大腸菌などの適当な宿主に導入して遺伝し工学的な手法により製造してもよい。また、式（I）又は(Ia)のペプチドのN末端は、メチル化もしくはアセチル化されていてもよく、C末端はメチルエステル、エチルエステル、プロピルエステル、ブチルエステルなどの炭素数１〜４のアルキル基とエステル化されていてもよく、アミド化（CONH2）されていてもよい。 The peptides of the formula (I) or (Ia) of the present invention may be produced by solid-phase synthesis, and the DNA encoding these peptides is introduced into an appropriate host such as Escherichia coli and inherited by an engineering method. It may be manufactured. Further, the N-terminal of the peptide of the formula (I) or (Ia) may be methylated or acetylated, and the C-terminal may have 1 to 4 carbon atoms such as methyl ester, ethyl ester, propyl ester and butyl ester. It may be esterified with an alkyl group or may be amidated (CONH2).
また、本発明のペプチドは、塩酸、硫酸、硝酸、メタンスルホン酸、トルエンスルホン酸などの有機酸もしくは無機酸と酸付加塩を形成してもよく、ナトリウム、カリウム、リチウムなどのアルカリ金属、カルシウム、マグネシウムなどのアルカリ土類金属と塩基塩を形成してもよい。 Further, the peptide of the present invention may form an acid addition salt with an organic acid or an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, methanesulfonic acid and toluenesulfonic acid, and an alkali metal such as sodium, potassium and lithium, and calcium. , May form a base salt with an alkaline earth metal such as magnesium.
本発明のペプチドは、粘膜細胞の増殖を促進することで炎症性腸疾患の粘膜創傷治癒を促進することができ、潰瘍性大腸炎、クローン病などの炎症性腸疾患の予防又は治療に有効である。 The peptide of the present invention can promote mucosal wound healing of inflammatory bowel disease by promoting the proliferation of mucosal cells, and is effective for prevention or treatment of inflammatory bowel disease such as ulcerative colitis and Crohn's disease. is there.
また、本発明のペプチドは、大腸がんの増殖を抑制できるので、大腸がんの治療に有効である。 Moreover, since the peptide of the present invention can suppress the growth of colorectal cancer, it is effective for the treatment of colorectal cancer.
本発明のペプチドは、錠剤、カプセル剤、顆粒剤、液剤などの経口剤により投与した場合、腸管粘膜から吸収されることにより大腸に作用してもよく、吸収されなかったペプチドは大腸表面の粘膜もしくはがんに直接作用して効果を発現してもよい。或いは、注射剤、坐剤などの非経口剤により投与してもよい。本発明のペプチドを大腸に直接作用させる場合、腸溶性コーティングした錠剤、顆粒剤などの経口剤として投与すると、腸内で分解されずに大腸まで到達するので、好ましい。 When the peptide of the present invention is administered as an oral preparation such as tablets, capsules, granules, and liquids, it may act on the large intestine by being absorbed from the intestinal mucosa, and the unabsorbed peptide may act on the large intestine. Alternatively, it may act directly on the cancer to exert its effect. Alternatively, it may be administered by a parenteral agent such as an injection or a suppository. When the peptide of the present invention is allowed to act directly on the large intestine, it is preferable to administer it as an oral preparation such as an enteric coated tablet or granule because it reaches the large intestine without being decomposed in the intestine.
本発明のペプチドの潰瘍性大腸炎、大腸がんに対する有効投与量は、いずれも成人１日当たり０．０１ｍｇ〜１０ｇ程度である。 The effective dose of the peptide of the present invention for ulcerative colitis and colorectal cancer is about 0.01 mg to 10 g per day for adults.
以下に実施例を示すが、本発明はこの実施例だけに限定されるものではない。 Examples are shown below, but the present invention is not limited to these examples.
本実施例で使用する配列番号２の36アミノ酸のペプチドの製造は、Invitragenに依頼し、質量分析の結果、理論値3906.53、実測値3906.40であった。
配列番号２：GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMR
The 36-amino acid peptide of SEQ ID NO: 2 used in this example was produced by Invitragen, and as a result of mass spectrometry, the theoretical value was 3906.53 and the measured value was 3906.40.
SEQ ID NO: 2: GVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMR
実施例１：マウス大腸癌皮下移植モデル
6週齢BALB-Cマウスの背側に培養したColon26（マウス大腸癌細胞株）を皮下移植（皮下注）し、同日より投与を開始した。PBS（200μl）連日腹腔内投与群をコントロール群、PBSに溶解した36アミノ酸の配列番号1のWnt5a ペプチド（20μg/200μl）の連日腹腔内投与群を治療群とした（各群５匹）。その後経時的に両群の腫瘍径を測定し、比較検討した。結果を図１に示す。
Example 1: Mouse colorectal cancer subcutaneous transplant model
Colon26 (mouse colon cancer cell line) cultured on the dorsal side of 6-week-old BALB-C mice was subcutaneously transplanted (subcutaneous injection), and administration was started on the same day. The daily intraperitoneal administration group of PBS (200 μl) was used as the control group, and the daily intraperitoneal administration group of Wnt5a peptide (20 μg / 200 μl) of SEQ ID NO: 1 of 36 amino acids dissolved in PBS was used as the treatment group (5 animals in each group). After that, the tumor diameters of both groups were measured over time and compared. The results are shown in FIG.
実施例２：Wnt5a 36AA peptideの創傷治癒効果
YAMC細胞（Young Adult Mouse Colonic epithelial cell）におけるwound healing assay（YAMC細胞を用いたwound healing assayに関する参考論文：Uchiyama K, et al., BBRC 391(2010) 1122-1126）において、配列番号1の36アミノ酸のペプチドの濃度が10ng/mlでYAMC細胞の創傷治癒を亢進した。
Example 2: Wound healing effect of Wnt5a 36AA peptide
In the wound healing assay in YAMC cells (Young Adult Mouse Colonic epithelial cells) (reference paper on wound healing assay using YAMC cells: Uchiyama K, et al., BBRC 391 (2010) 1122-1126), 36 of SEQ ID NO: 1. The amino acid peptide concentration of 10 ng / ml enhanced wound healing of YAMC cells.
Claims (3)
Colorectal cancer therapeutic agent comprising as an active ingredient the peptide of claim 1.
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