JP6050319B2 - 活性ポリペプチドの結合親和力及び結合特異性を増強させる蛋白質骨格モジュール - Google Patents
活性ポリペプチドの結合親和力及び結合特異性を増強させる蛋白質骨格モジュール Download PDFInfo
- Publication number
- JP6050319B2 JP6050319B2 JP2014506324A JP2014506324A JP6050319B2 JP 6050319 B2 JP6050319 B2 JP 6050319B2 JP 2014506324 A JP2014506324 A JP 2014506324A JP 2014506324 A JP2014506324 A JP 2014506324A JP 6050319 B2 JP6050319 B2 JP 6050319B2
- Authority
- JP
- Japan
- Prior art keywords
- present
- protein
- active polypeptide
- protein backbone
- polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 165
- 108090000623 proteins and genes Proteins 0.000 title claims description 153
- 102000004169 proteins and genes Human genes 0.000 title claims description 151
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 140
- 229920001184 polypeptide Polymers 0.000 title claims description 137
- 230000027455 binding Effects 0.000 title description 49
- 108010018242 Transcription Factor AP-1 Proteins 0.000 claims description 48
- 102100023118 Transcription factor JunD Human genes 0.000 claims description 48
- 108091033319 polynucleotide Proteins 0.000 claims description 30
- 102000040430 polynucleotide Human genes 0.000 claims description 30
- 239000002157 polynucleotide Substances 0.000 claims description 30
- 206010028980 Neoplasm Diseases 0.000 claims description 29
- 239000004480 active ingredient Substances 0.000 claims description 24
- 239000013604 expression vector Substances 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 22
- 201000011510 cancer Diseases 0.000 claims description 20
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 18
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 238000009007 Diagnostic Kit Methods 0.000 claims description 5
- 238000012258 culturing Methods 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 150000001413 amino acids Chemical group 0.000 description 47
- 210000004027 cell Anatomy 0.000 description 33
- 238000000034 method Methods 0.000 description 22
- 238000001514 detection method Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 102000010787 Interleukin-4 Receptors Human genes 0.000 description 12
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 239000013598 vector Substances 0.000 description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical group O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- -1 radioisotope Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 102100024470 Stabilin-2 Human genes 0.000 description 5
- 101710164033 Stabilin-2 Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 3
- 102100023980 Signal transducer and activator of transcription 6 Human genes 0.000 description 3
- 229920002472 Starch Chemical class 0.000 description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 description 3
- 239000001913 cellulose Chemical class 0.000 description 3
- 229920002678 cellulose Chemical class 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000013076 target substance Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 206010046766 uterine cancer Diseases 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical class O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 2
- 239000004366 Glucose oxidase Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 241000723873 Tobacco mosaic virus Species 0.000 description 2
- 102000000887 Transcription factor STAT Human genes 0.000 description 2
- 108050007918 Transcription factor STAT Proteins 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- MURGITYSBWUQTI-UHFFFAOYSA-N fluorescin Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC=C(O)C=C2OC2=CC(O)=CC=C21 MURGITYSBWUQTI-UHFFFAOYSA-N 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 229940116332 glucose oxidase Drugs 0.000 description 2
- 235000019420 glucose oxidase Nutrition 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000012137 tryptone Substances 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- ZTOJFFHGPLIVKC-YAFCTCPESA-N (2e)-3-ethyl-2-[(z)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S\1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C/1=N/N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-YAFCTCPESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 108050009406 C-type lectin-like Proteins 0.000 description 1
- 102000002086 C-type lectin-like Human genes 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- QAHFOPIILNICLA-UHFFFAOYSA-N Diphenamid Chemical compound C=1C=CC=CC=1C(C(=O)N(C)C)C1=CC=CC=C1 QAHFOPIILNICLA-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000672609 Escherichia coli BL21 Species 0.000 description 1
- 241001288713 Escherichia coli MC1061 Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 101000731000 Homo sapiens Membrane-associated progesterone receptor component 1 Proteins 0.000 description 1
- 101001074035 Homo sapiens Zinc finger protein GLI2 Proteins 0.000 description 1
- 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 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
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102100032399 Membrane-associated progesterone receptor component 1 Human genes 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091000041 Phosphoenolpyruvate Carboxylase Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 239000012327 Ruthenium complex Substances 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 102100035558 Zinc finger protein GLI2 Human genes 0.000 description 1
- ATQVBSVAXDRWFW-HBMCJLEFSA-N [(1r)-2-(4-hydroxyphenyl)-1-[[(2s)-1-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]ethyl]phosphonic acid Chemical compound C([C@@H](C(=O)NC(=O)[C@H](C(C)C)NC)N[C@@H](CC=1C=CC(O)=CC=1)P(O)(O)=O)C1=CC=CC=C1 ATQVBSVAXDRWFW-HBMCJLEFSA-N 0.000 description 1
- 239000005092 [Ru (Bpy)3]2+ Substances 0.000 description 1
- ZTOJFFHGPLIVKC-CLFAGFIQSA-N abts Chemical compound S/1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C\1=N\N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-CLFAGFIQSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 150000001615 biotins Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910001417 caesium ion Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 229940124466 diagnostic for cancer Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000008202 granule composition Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 108010029257 guanosine-diphosphatase Proteins 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- RXNXLAHQOVLMIE-UHFFFAOYSA-N phenyl 10-methylacridin-10-ium-9-carboxylate Chemical compound C12=CC=CC=C2[N+](C)=C2C=CC=CC2=C1C(=O)OC1=CC=CC=C1 RXNXLAHQOVLMIE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- YVSWPCCVTYEEHG-UHFFFAOYSA-N rhodamine B 5-isothiocyanate Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(N=C=S)C=C1C(O)=O YVSWPCCVTYEEHG-UHFFFAOYSA-N 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical class [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Chemical class 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001180 sulfating effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/485—Epidermal growth factor [EGF], i.e. urogastrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5406—IL-4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Plant Pathology (AREA)
Description
a)配列番号1で示されるアミノ酸配列の1番目乃至19番目のアミノ酸配列からなるポリペプチド;
b)活性ポリペプチドを含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とする活性ポリペプチドが内蔵された蛋白質骨格モジュールを提供することである。
本発明の他の目的は前記宿主細胞を培養する段階を含む活性ポリペプチドが内蔵された蛋白質骨格モジュールを製造する方法を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用組成物を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを必要とする個体に有効量で投与する段階を含む診断方法を提供することである。
本発明の他の目的は診断用製剤の製造のための前記活性ポリペプチドが内蔵された蛋白質骨格モジュールの用途を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む薬学的組成物を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用キットを提供することである。
本発明の他の目的は
a)配列番号1で示されるアミノ酸配列の1番目乃至19番目のアミノ酸配列からなるポリペプチド;
b)配列番号3で示されるAP-1(activator protein 1)のアミノ酸配列を含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とする活性ポリペプチドが内蔵された蛋白質骨格モジュールを提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを符号化するポリヌクレオチドを提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用組成物を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを必要とする個体に有効量で投与する段階を含む癌又は動脈硬化診断方法を提供することである。 本発明の他の目的は癌又は動脈硬化診断用製剤の製造のための前記活性ポリペプチドが内蔵された蛋白質骨格モジュールの用途を提供することである。
本発明の他の目的は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用キットを提供することである。
a)配列番号1で示されるアミノ酸配列1番目乃至29番目のアミノ酸配列からなるポリペプチド;
b)活性ポリペプチドを含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とする活性ポリペプチドが内蔵された蛋白質骨格モジュールを提供する。
本発明の他の目的を達成するために、本発明は前記ポリヌクレオチドを含む発現ベクターを提供する。
本発明の他の目的を達成するために、本発明は前記発現ベクターに形質転換された宿主細胞を提供する。
本発明の他の目的を達成するために、本発明は前記宿主細胞を培養する段階を含む活性ポリペプチドが内蔵された蛋白質骨格モジュールを製造する方法を提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用組成物を提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを必要とする個体に有効量で投与する段階を含む診断方法を提供する。 本発明の他の目的を達成するために、本発明は診断用製剤の製造のための前記活性ポリペプチドが内蔵された蛋白質骨格モジュールの用途を提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む薬学的組成物を提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用キットを提供する
本発明の他の目的を達成するために、本発明は
a)配列番号1で示されるアミノ酸配列の1番目乃至19番目のアミノ酸配列からなるポリペプチド;
b)配列番号3で示されるAP-1(activator protein 1)のアミノ酸配列を含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とする活性ポリペプチドが内蔵された蛋白質骨格モジュールを提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを符号化するポリヌクレオチドを提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用組成物を提供する。
本発明の他の目的を達成するために、本発明は前記活性ポリペプチドが内蔵された蛋白質骨格モジュールを要とする個体に有効量で投与する段階を含む癌又は動脈硬化の診断方法を提供する。
本発明の他の目的を達成するために、本発明は癌又は動脈硬化診断用製剤の製造のための前記活性ポリペプチドが内蔵された蛋白質骨格モジュールの用途を提供する。
本発明の他の目的を達成するために、本発明は活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用キットを提供する。
a)配列番号1で示されるアミノ酸配列の1番目乃至19番目のアミノ酸配列からなるポリペプチド;
b)配列番号3で示されるAP-1(activator protein 1)のアミノ酸配列を含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とするAP-1が内蔵された蛋白質骨格モジュール、及び
前記AP-1が内蔵された蛋白質骨格モジュールを符号化するポリヌクレオチドを提供する。
DMID(Designed Modular Immunodiagnosties)候補郡スクリーニング及びモデリング
1−1.スクリーニング
ヒトから発現される蛋白質ドメイン内に多量に存在するmodularドメインをヒトの遺伝子データベースを比較分析するポストジノミックスクリーニングを通じて20個の候補郡に選定した後、a)高い親和力、b)低い分子量、c)低い免疫原性(low immunogenicity)、d)ヒトに豊富に存在、及びe)3次元構造検証可能な条件を基準にEGFL(EGF-like)ドメインを選定した。
EGFLドメインの3次元モデリングのためにBLASTとAlignMasterプログラムが使用された。ヒトのEGFLドメインの構造はProtein DataBankから提供された。
組換えDMID-AP1発現及び精製
2−1.形質転換菌株製作-DMID-SalI-HindIII cassetteの製作
本発明の蛋白質骨格モジュール(DMID)を製作するためにスタビリン2蛋白質が存在するEGFLドメイン(4621-4869)をE-coli発現ベクターであるpET32a(Novagen)のBamH1とXhol siteにクローニングして発現蛋白質を製造した。EGFLドメインのGCTGAC(4639-4644)をGTCGACで遺伝子変異を起こし、制限酵素Sall siteを製造してAAAGCA(4703-4708)をAAGCTTで変異を起こして制限酵素HindIIIsiteを製造し、活性ポリペプチドを挿入できるDMID-Sall-HindIII casseteを製造した。
形質転換されたOrigami strainを50ug/mlのAmpicilinと25ug/mlのKanamycinが含まれた20mlのTryptone phosphate(TP)broth (2% bacto-tryptone,0.2% Na2 HPO4 ,0.1% KH2 PO4 ,0.8%NaCl,1.5% yeast extret and 0.2%glcose)夜通し培養した。
前記保管された細胞を1mM PMSF,0.5mM DTTが含まれた10ml of 2X PBSに再懸濁して、Duty cycle:30%,Output:2.5 for 5 minの条件で超音波粉砕した。粉砕された細胞を15,000gに10分間遠心分離して上澄液を採取した。
組換えDMID-AP1結合能力向上検証―表面プラズモン共鳴分析
本発明のAP1が内蔵された蛋白質骨格モジュール(DMID-AP1)の結合能力を調べるためにnaked AP1とDMID-AP1の結合定数をBiacore 2000を使用して表面プラズモン共鳴分析法で測定した。昆虫細胞(SF21)で発現及び精製したヒトのIL-4 レセプタのectodomain(IL-4Ra)をHBR 緩衝液(10 mM HEPES,pH7.4,150 mM NaCl,3.4mM EDTA,and 0.005% surfant P20)に希釈した後、Biacore CM5 chip表面に製造社の方法によりコーティングした(2500 RU)。同一緩衝液に希釈したAP-1ペプチド又はDMID-AP1を流して(50 ul/min)RU値の変化を測定した後、Biaevaluation2.0プログラムを使用して結合定数を求めた。
組換えDMID-API 検出能力向上検証1-IL-4によるIL-4 レセプタの活性阻害度の測定
5X105 のTHP1(NIH AIDS Research and Reagent Program,NCI9949)細胞を6-well plateに播種(seeding)後100ng/mlのPhorbol12-myristate13-acetate(PMA)(Sigma,P8139-1MG)を3日間処理して活性化(activate)させた。18時間血清(serum)がない条件で細胞を培養した後、0.67nM(1X)のIL-4単独又は多様な濃度[10n X (0.67NM)]のAP-1 peptide又は組換えDMID-AP1を共に処理した。IL-4とIL-4 レセプタ間の結合により誘導されたStat蛋白質のリン酸化はRabbit polyclonal antibody anti-STAT6(Cell Signaling,#9362)とRabbit polyclonal antibody anti-pTyr641-STAT6(Cell Signaling,#9361)を使用してウェスタンブット法で測定した。その結果、図4に示した通り、本発明のDMID-AP1がAP1に比べてStat蛋白質をリン酸化するIL-4活性を10倍以上阻害することを確認した。
組換えDMID-AP1 検出能力向上検証2-細胞影像,動物影像
5−1.細胞影像(Cellular imaging)
本発明のAP1が内蔵された蛋白質骨格モジュール(DMID-AP1)の細胞に発現されたIL-4レセプタとの競争的結合能力を調べるために、H226 cell lineにおけるnaked AP1とDMID-AP1のIL-4 レセプタに対する結合能力を蛍光標識された蛋白質を使用して測定した。AP-1ペプチド又は精製されたDMID-AP1を透析緩衝液(50mM Boric acid,150mM NaCl,1mM EDTA,pH 9.0)で4℃で透析した後、蛍光物質Fluorescein Isothiocyanate(FITC)(sigma)と37℃で1時間反応させて標識した。50mM Glycineを37℃で5分間入れて反応を中止後、透析緩衝液(20mM Tris HCl,pH8.0)で4℃で透析した。H226 cellにそれぞれ同一な量の対照群ペプチド、AP-1、DMID-AP1を添加して結合、洗滌後 4%paraformaldehyde(PFA)で固定して細胞核は4',6-diamidino-2-phenylindole(DAPI)で染色後、蛍光顕微鏡(Zeiss,Oberkochen,Germany)で観察した。
1X107個のH226細胞を培養培地に浮遊させて、5〜6週齢の雌BALB/c nudeマウスの右側大腿部に皮下注射して皮下腫瘍モデルを製造した。約3週後腫瘍の大きさが0.1〜1cmになった時実験に使用した。腫瘍異種移植マウスを麻酔させて蛍光物質が結合されたAP-1ペプチドとDMID-AP1 150 ugを尻尾部分の静脈に注射した。蛍光標識されたペプチドの腫瘍ターゲッティング機能をOpticsを利用して分析した。
Claims (12)
- a)配列番号1で示されるアミノ酸配列の1番目乃至19番目のアミノ酸配列からなるポリペプチド;
b)配列番号3で示されるAP-1(activator protein 1)のアミノ酸配列からなる活性ポリペプチドを含むポリペプチド及び
c)配列番号1で示されるアミノ酸配列の29番目乃至86番目のアミノ酸配列からなるポリペプチドが順次に連結されたポリペプチドを含むことを特徴とする活性ポリペプチドが内蔵された蛋白質骨格モジュール。 - 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを符号化するポリヌクレオチド。
- 請求項2記載のポリヌクレオチドを含む発現ベクター。
- 請求項3記載の発現ベクターに形質転換された宿主細胞。
- 請求項4記載の宿主細胞を培養する段階を含む請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを製造する方法。
- 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用組成物。
- 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む薬学的組成物。
- 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む診断用キット。
- 前記ポリヌクレオチドは配列番号4乃至配列番号6の塩基配列からなる群より選ばれたいずれか一つであることを特徴とする請求項2記載のポリヌクレオチド。
- 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用組成物。
- 請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールを有効成分として含む癌又は動脈硬化診断用キット。
- 癌又は動脈硬化診断用製剤の製造のための請求項1記載の活性ポリペプチドが内蔵された蛋白質骨格モジュールの使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2011-0035613 | 2011-04-18 | ||
KR1020110035613A KR101818759B1 (ko) | 2011-04-18 | 2011-04-18 | 활성 폴리펩타이드의 결합 친화력 및 결합 특이성을 증강시키는 단백질 골격 모듈 |
PCT/KR2012/002958 WO2012144799A2 (ko) | 2011-04-18 | 2012-04-18 | 활성 폴리펩타이드의 결합 친화력 및 결합 특이성을 증강시키는 단백질 골격 모듈 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014519313A JP2014519313A (ja) | 2014-08-14 |
JP6050319B2 true JP6050319B2 (ja) | 2016-12-21 |
Family
ID=47042041
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014506324A Expired - Fee Related JP6050319B2 (ja) | 2011-04-18 | 2012-04-18 | 活性ポリペプチドの結合親和力及び結合特異性を増強させる蛋白質骨格モジュール |
Country Status (6)
Country | Link |
---|---|
US (1) | US8975369B2 (ja) |
EP (1) | EP2700649B1 (ja) |
JP (1) | JP6050319B2 (ja) |
KR (1) | KR101818759B1 (ja) |
CN (1) | CN103703022A (ja) |
WO (1) | WO2012144799A2 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101604375B1 (ko) * | 2013-02-08 | 2016-03-25 | 경북대학교 산학협력단 | 인간 페리틴 유래 융합폴리펩티드 |
KR102028250B1 (ko) * | 2017-10-17 | 2019-11-04 | 전북대학교산학협력단 | 대장균 선별용 펩타이드 |
CN112289372B (zh) * | 2020-12-15 | 2022-04-22 | 武汉华美生物工程有限公司 | 一种基于深度学习的蛋白质结构设计方法及装置 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050287638A1 (en) * | 2000-04-25 | 2005-12-29 | Weigel Paul H | Hyaluronan receptor for endocytosis, variants thereof, and methods of making and using same |
AU2002246808A1 (en) * | 2000-12-19 | 2002-08-06 | Curagen Corporation | Human nucleic acids and polypeptides and methods of use thereof |
US20030232013A1 (en) * | 2002-02-22 | 2003-12-18 | Gary Sieckman | Therapeutic and diagnostic targeting of cancers cells with tumor homing peptides |
KR100870233B1 (ko) * | 2007-04-05 | 2008-11-24 | 경북대학교 산학협력단 | 동맥경화 진단, 예방 및 치료용 펩타이드 및 이의 용도 |
KR101196799B1 (ko) * | 2008-02-25 | 2012-11-05 | 경북대학교 산학협력단 | 스태빌린-2의 egf-유사 도메인의 반복부위 단편을포함하는 폴리펩티드, 이를 포함하는 포스파티딜세린검출용 조성물 및 이의 용도 |
US20110077581A1 (en) * | 2009-09-25 | 2011-03-31 | Georgia Tech Research Corporation | Targeted cellular delivery of nanoparticles |
-
2011
- 2011-04-18 KR KR1020110035613A patent/KR101818759B1/ko active IP Right Grant
-
2012
- 2012-04-18 EP EP12773577.7A patent/EP2700649B1/en not_active Not-in-force
- 2012-04-18 CN CN201280029758.7A patent/CN103703022A/zh active Pending
- 2012-04-18 WO PCT/KR2012/002958 patent/WO2012144799A2/ko active Application Filing
- 2012-04-18 JP JP2014506324A patent/JP6050319B2/ja not_active Expired - Fee Related
-
2013
- 2013-10-18 US US14/057,654 patent/US8975369B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
KR20120118186A (ko) | 2012-10-26 |
KR101818759B1 (ko) | 2018-01-16 |
WO2012144799A3 (ko) | 2013-01-17 |
EP2700649A2 (en) | 2014-02-26 |
EP2700649A4 (en) | 2014-12-24 |
US8975369B2 (en) | 2015-03-10 |
US20140079643A1 (en) | 2014-03-20 |
JP2014519313A (ja) | 2014-08-14 |
EP2700649B1 (en) | 2016-12-21 |
CN103703022A (zh) | 2014-04-02 |
WO2012144799A2 (ko) | 2012-10-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6486908B2 (ja) | 肝細胞増殖因子に結合する設計アンキリン反復タンパク質 | |
US11578427B2 (en) | Designed ankyrin repeat domains with altered surface residues | |
AU2021215151B2 (en) | SIRP-alpha variant constructs and uses thereof | |
PT1107989E (pt) | Expresso e exportaão de angiostatina e endostatina na forma de imunofusinas | |
KR20120097481A (ko) | 사람 혈청 알부민(HSA)의 변이체와 컨쥬게이션된 αvβ3 인테그린에 대해 선택적인 폴리펩타이드 및 이의 약제학적 용도 | |
Mohajeri et al. | The challenges of recombinant endostatin in clinical application: Focus on the different expression systems and molecular bioengineering | |
JP2017525394A (ja) | ディスインテグリンバリアントとその医薬用途 | |
JP6050319B2 (ja) | 活性ポリペプチドの結合親和力及び結合特異性を増強させる蛋白質骨格モジュール | |
JP5445975B2 (ja) | Tnf受容体の可溶性変異体 | |
US11306147B2 (en) | Single chain fusionconstructs comprising multimeric antibody fragments fused to collagen trimerization domains | |
TW201908337A (zh) | 活性型mmp-9結合肽 | |
AU769933B2 (en) | Angiostatin-binding protein | |
CN111647074B (zh) | 一种her3二聚化界面抗原肽、重组抗原肽、编码基因及其应用 | |
WO2015090234A1 (en) | Improving pharmacokinetic profile for angiopoietin-2 inhibiting polypeptide or thymalfasin | |
JP2002528120A (ja) | 細胞透過媒介性ポリペプチド | |
US10550169B2 (en) | Oligomers for TNF superfamily inhibition, methods of making and using | |
CN114057888A (zh) | 一种SIRPα-Fc融合蛋白 | |
US20230312737A1 (en) | Anti-dr5 polypeptides and methods of use thereof | |
CN113018418B (zh) | 微小RNA31前体编码多肽miPEP31在制备高血压药物中的应用 | |
KR102675219B1 (ko) | Sirp-알파 변이체 구성체 및 이의 용도 | |
WO2021257961A1 (en) | Compositions and methods for treating cancer | |
WO2011079431A1 (zh) | 具有端粒酶抑制活性的融合蛋白、其制备方法和用途 | |
MXPA00011922A (en) | Angiostatin-binding protein |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150402 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160315 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160610 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161025 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161124 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6050319 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |