JP6820251B2 - 病原菌に対する抗生活性を有するペプチド及びこれを含む抗生ペプチド組成物 - Google Patents
病原菌に対する抗生活性を有するペプチド及びこれを含む抗生ペプチド組成物 Download PDFInfo
- Publication number
- JP6820251B2 JP6820251B2 JP2017510404A JP2017510404A JP6820251B2 JP 6820251 B2 JP6820251 B2 JP 6820251B2 JP 2017510404 A JP2017510404 A JP 2017510404A JP 2017510404 A JP2017510404 A JP 2017510404A JP 6820251 B2 JP6820251 B2 JP 6820251B2
- Authority
- JP
- Japan
- Prior art keywords
- antibiotic
- peptide
- present
- peptides
- activity against
- 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.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 94
- 230000003115 biocidal effect Effects 0.000 title claims description 78
- 239000000203 mixture Substances 0.000 title claims description 15
- 244000052769 pathogen Species 0.000 title claims description 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 36
- 239000003242 anti bacterial agent Substances 0.000 claims description 22
- 241000894006 Bacteria Species 0.000 claims description 18
- 241000607142 Salmonella Species 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 8
- 241000191967 Staphylococcus aureus Species 0.000 claims description 7
- 241000588724 Escherichia coli Species 0.000 claims description 6
- 241000186805 Listeria innocua Species 0.000 claims description 5
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 description 29
- 230000000844 anti-bacterial effect Effects 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229940088710 antibiotic agent Drugs 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 241000192125 Firmicutes Species 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 2
- 101800002011 Amphipathic peptide Proteins 0.000 description 2
- 239000004475 Arginine Substances 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
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000005452 food preservative Substances 0.000 description 2
- 235000019249 food preservative Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000008020 pharmaceutical preservative Substances 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- -1 secropin Proteins 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 1
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 1
- 101710114744 Bombinin Proteins 0.000 description 1
- 229940123150 Chelating agent Drugs 0.000 description 1
- 241000555825 Clupeidae Species 0.000 description 1
- 108010002069 Defensins Proteins 0.000 description 1
- 102000000541 Defensins Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 238000002768 Kirby-Bauer method Methods 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108060003100 Magainin Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 108010070741 Tachypleus tridentatus tachyplesin peptide Proteins 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 238000011482 antibacterial activity assay Methods 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 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
- 238000003149 assay kit Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000692 cap cell Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000013003 healing agent Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ZJQFYZCNRTZAIM-PMXBASNASA-N tachyplesin Chemical compound C([C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@H](C(N[C@H]2CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=3C=CC=CC=3)NC(=O)[C@@H](NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](N)CCCCN)CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC2=O)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)N1)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZJQFYZCNRTZAIM-PMXBASNASA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K4/00—Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof
- C07K4/12—Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
[(N−末端)−NKVKEWX1KX2LKX3X4FX5−(C−末端)]
前述したように、牛の牛乳に存在するラクトフォリシン(LPcin−I)は、23個のアミノ酸残基を有する陽イオン、両親媒性ペプチドであって、PP3のカルボキシ末端113〜135領域である。LPcin−Iは、グラム−陽性菌とグラム−陰性菌の両方の成長を抑制するが、200μM以下の濃度で溶血作用が現われない。ところが、抗生能があるものと知られたLPcin−Iを商業化するために、野生型LPcin−Iより高い抗生能及び製造コストを低減する必要があり、そのために、さらに短いアミノ酸配列よりなる抗生ペプチドを製造する技術開発がますます要請されている。
[(N−末端)−NKVKEWX1KX2LKX3X4FX5−(C−末端)]
新規な抗菌ペプチドの製造
自動ペプチド合成器(Milligen 9050、Millipore、米国)を利用して下記表1に記載した配列のペプチドを合成し、これら合成されたペプチドをpreparative逆相高分解能液体クロマトグラフィー(Shiseido capcell pak C18 columnを使用したShimadzu Prominence HPLC)を利用して純粋分離した。
抗菌活性測定実験
前記実施例1で合成した1〜11番の11個のペプチドに対して抗生活性を測定した。具体的に、微生物に対する抗生活性は、ブレインハートインフュージョン(Brain heart infusion)agar(BactoTM)を使用して行った。二つのグラム−陽性菌(Listeria innocua MC2 KCTC 3658及びStaphylococcus aureus ATCC 6538)と三つのグラム−陰性菌(Pseudomonas aeruginosa ATCC 27853、Salmonella ATCC 19430、Escherichia coli KCTC 1682)の五つの微生物に対して寒天ディスク拡散(agar disc diffusion)テストを基礎にした。接種源は、37℃、3.7%ブレインハートインフュージョン(Brain heart infusion)5mlでバクテリアを一晩培養するものを準備した。懸濁液の混濁程度は、600nmで分光光度計で0.05標準濁度液(1x108CFU/mL)のように最終濃度を調節した。20mlのブレインハートインフュージョン(Brain heart infusion)寒天をφ90mmの細胞培養プレートに塗布した。寒天(Agar)プレートに滅菌されたスプレッダー(spreader)を使用して30ulのバクテリア懸濁液を接種させた。接種された寒天プレートは、30分間常温で乾燥した。寒天プレートの表面に滅菌された6mmのろ紙(Whatman No.1)を位置させ、抗生ペプチドは、10mMの濃度で滅菌物にとかして、20ulの溶液をろ紙に接種させた。常温で30分間pre−diffusionをさせた後、プレートを37℃で24時間培養した。24時間が経過した後、ろ紙周辺のバクテリア群の成長抑制直径を測定することによって、バクテリア群に対する抗生ペプチドの敏感度は、バクテリア生長を抑制する領域のサイズと除去した程度によって決定した。測定は、2回繰り返して行われた。
細胞毒性実験
Cyto XTM cell viability assay kit(LPS solution)試験法を利用して細胞毒性実験を実施した。96−ウェル細胞培養プレートは、corning社から購入し、哺乳細胞株は、ATCCから購入した。また、Cyto XTM細胞可視分析キットは、LPS solutionから購入した。
最小抑制濃度測定実験
抗菌アッセイは、標準ブロス微量希釈法(broth microdilution method)を利用して最小抑制濃度(minimal inhibitory concentration、MIC)値を測定することによって行った。各ペプチドの抗菌活性は、二つのグラム−陽性菌(Listeria innocua MC2 KCTC 3658及びStaphylococcus aureus ATCC 6538)と三つのグラム−陰性菌(Pseudomonas aeruginosa ATCC27853、Salmonella ATCC 19430、Escherichia coli KCTC 1682)を利用して行った。この5種の菌を50μlで準備した後、5mlの3.7%BHIに混合し、一晩37℃、240rpm条件で培養した。その後、培養された菌50μlを5mlの3.7%BHIに混合し、2時間、37℃、240rpm条件で培養した。培養した菌は、0.037%BHI溶液で希釈し、1×108CFU/mlの濃度で準備した。
Claims (4)
- 病原菌に対する抗生活性を有する下記配列[一般式I]で表現されるペプチド:
[一般式I]
[(N−末端)−NKVKEWX1KX2LKX3X4FX5−(C−末端)]
ここで、X1はI又はWであり;X1がIであれば、X2はYであり、X1がWであれば、X2はWであり;X3はS又はKであり;X4はL又はKであり;X5はS又はKである。
ここで、NKVKEWIKYLKSLFSのアミノ酸配列(配列番号1)によって表されるペプチドは除く。 - 病原菌に対する抗生活性を有する下記配列[一般式I]で表現されるペプチド:
[一般式I]
[(N−末端)−NKVKEWX 1 KX 2 LKX 3 X 4 FX 5 −(C−末端)]
ここで、X 1 はI又はWであり;X 1 がIであれば、X 2 はYであり、X 1 がWであれば、X 2 はWであり;X 3 X 4 FX 5 は欠失されているか、又は
X 1 はI又はWであり;X 1 がIであれば、X 2 はYであり、X 1 がWであれば、X 2 はWであり;X 3 はS又はKであり;X 4 はL又はKであり;FX 5 は欠失されている。 - 請求項1又は2に記載の抗生ペプチドを有効成分として含有する抗生ペプチド組成物。
- 前記抗生活性は、ブドウ球菌(Staphylococcus aureus)、サルモネラ菌(Salmonella)、リステリア・イノキュア(Listeria innocua)、緑膿菌(Pseudomonas aeruginosa)、及び大腸菌(Escherichia coli)よりなる群から選択されるいずれか一つ以上の菌に対する抗生活性であることを特徴とする請求項3に記載の抗生ペプチド組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020160051073A KR101847051B1 (ko) | 2016-04-26 | 2016-04-26 | 병원균에 대한 항생활성을 갖는 펩타이드 및 이를 포함하는 항생 펩타이드 조성물 |
KR10-2016-0051073 | 2016-04-26 | ||
PCT/KR2016/005513 WO2017188498A1 (ko) | 2016-04-26 | 2016-05-25 | 병원균에 대한 항생활성을 갖는 펩타이드 및 이를 포함하는 항생 펩타이드 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019523211A JP2019523211A (ja) | 2019-08-22 |
JP6820251B2 true JP6820251B2 (ja) | 2021-01-27 |
Family
ID=60159744
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017510404A Active JP6820251B2 (ja) | 2016-04-26 | 2016-05-25 | 病原菌に対する抗生活性を有するペプチド及びこれを含む抗生ペプチド組成物 |
Country Status (4)
Country | Link |
---|---|
US (1) | US10150795B2 (ja) |
JP (1) | JP6820251B2 (ja) |
KR (1) | KR101847051B1 (ja) |
WO (1) | WO2017188498A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11174288B2 (en) | 2016-12-06 | 2021-11-16 | Northeastern University | Heparin-binding cationic peptide self-assembling peptide amphiphiles useful against drug-resistant bacteria |
CN111909243B (zh) * | 2020-08-04 | 2022-01-18 | 立康荣健(北京)生物医药科技有限公司 | 一种抗菌肽和抗菌止痒药物组合物及应用 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003295520B8 (en) | 2002-11-12 | 2011-05-19 | The Brigham And Women's Hospital, Inc. | Polysaccharide vaccine for Staphylococcal infections |
KR101081814B1 (ko) | 2008-12-19 | 2011-11-09 | 한국외국어대학교 연구산학협력단 | LPcin-Ⅰ펩타이드 또는 LPcin-Ⅱ 펩타이드를 포함하는 재조합 발현벡터 및 이를 이용한 펩타이드의 대량생산방법 |
KR20100123272A (ko) | 2009-05-15 | 2010-11-24 | 한국외국어대학교 연구산학협력단 | 강력한 항 감염성 활성을 갖는 사람-락토페리신 단백질 단편 생산 재조합 균주 및 그 균주를 이용한 사람-락토페리신 생산방법 |
KR101257222B1 (ko) | 2011-05-25 | 2013-04-29 | 한국외국어대학교 연구산학협력단 | 미생물에 대한 항생활성을 갖는 펩타이드 및 이를 포함하는 항생 펩타이드 조성물 |
WO2013041663A2 (de) * | 2011-09-22 | 2013-03-28 | Amp-Therapeutics Gmbh | Modifizierte apidaecinderivate als antibiotische peptide |
KR101345333B1 (ko) | 2011-12-30 | 2013-12-30 | 조선대학교산학협력단 | 라이신 및 트립토판 잔기가 4번 반복된 신규한 항균 및 항진균 펩타이드 및 이의 용도 |
US9567367B2 (en) | 2012-01-16 | 2017-02-14 | Atox Bio Ltd. | Synthetic peptides for treatment of bacterial infections |
-
2016
- 2016-04-26 KR KR1020160051073A patent/KR101847051B1/ko active IP Right Grant
- 2016-05-25 US US15/512,193 patent/US10150795B2/en active Active
- 2016-05-25 JP JP2017510404A patent/JP6820251B2/ja active Active
- 2016-05-25 WO PCT/KR2016/005513 patent/WO2017188498A1/ko active Application Filing
Also Published As
Publication number | Publication date |
---|---|
US10150795B2 (en) | 2018-12-11 |
KR101847051B1 (ko) | 2018-04-09 |
KR20170122026A (ko) | 2017-11-03 |
JP2019523211A (ja) | 2019-08-22 |
US20180170965A1 (en) | 2018-06-21 |
WO2017188498A1 (ko) | 2017-11-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Romanelli et al. | Peptides from Royal Jelly: studies on the antimicrobial activity of jelleins, jelleins analogs and synergy with temporins | |
JP4484941B2 (ja) | 生物活性を有する短ペプチド及び該ペプチドの使用方法 | |
DK2938352T3 (en) | CYLIC CATIONIC PEPTIDES WITH ANTIBMICROBIAL ACTIVITY | |
KR101896927B1 (ko) | 흰점박이꽃무지에서 유래한 항균 펩타이드 프로테티아마이신 1 및 그의 조성물 | |
KR102499670B1 (ko) | 라이신 치환을 포함하는 Romo1 유래 항균 펩타이드 및 그 변이체 | |
KR101341210B1 (ko) | 신규한 항균 펩타이드 및 이의 용도 | |
US20080234188A1 (en) | Antimicrobial Peptides | |
JP6820251B2 (ja) | 病原菌に対する抗生活性を有するペプチド及びこれを含む抗生ペプチド組成物 | |
KR101740551B1 (ko) | 벼메뚜기에서 유래한 항균 펩타이드 옥시야신-2 및 그의 조성물 | |
KR100836596B1 (ko) | 높은 염농도에서 항균 활성을 갖는 펩타이드들 및 이들을포함하는 항균 조성물 | |
Kim et al. | Effects of the synthetic coprisin analog peptide, CopA3 in pathogenic microorganisms and mammalian cancer cells | |
KR101953834B1 (ko) | 왕귀뚜라미에서 유래한 항균 펩타이드 테레오그릴루신 2 및 그의 조성물 | |
KR20170053879A (ko) | 벼메뚜기에서 유래한 항균 펩타이드 옥시야신-1 및 그의 조성물 | |
KR100441402B1 (ko) | 항균 활성을 갖는 펩타이드, 이들의 유도체 및 이들을포함하는 항균 조성물 | |
AU2002317071A1 (en) | Antimicrobial peptides | |
CN115043924B (zh) | 一种改造体抗菌肽及其应用 | |
JP2006519217A (ja) | 抗菌剤 | |
KR101257222B1 (ko) | 미생물에 대한 항생활성을 갖는 펩타이드 및 이를 포함하는 항생 펩타이드 조성물 | |
KR20170131909A (ko) | 벼메뚜기에서 유래한 항균 펩타이드 옥시야신-3 및 그의 조성물 | |
Chanu et al. | Structure-activity relationship of buffalo antibacterial hepcidin analogs | |
TW201520231A (zh) | 耐高鹽及抗蛋白之抗菌胜肽及其製造方法 | |
Park et al. | Isolation and functional analysis of a 24‐residue linear α‐helical antimicrobial peptide from Korean blackish cicada, Cryptotympana dubia (Homoptera) | |
Sánchez et al. | In vitro determination of the short-chain synthetic peptide RP13 antimicrobial activity | |
CZ2008128A3 (cs) | Nové peptidy, zpusob jejich prípravky a jejich použití | |
KR20020069150A (ko) | 항암 및 항생활성을 갖는 신규 폴리펩티드와 그를함유하는 항암제 및 항생제 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190201 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190201 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200204 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200507 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200706 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200728 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201028 |
|
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: 20201201 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210104 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6820251 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |