JP5335241B2 - 抗微生物ヘキサペプチド - Google Patents
抗微生物ヘキサペプチド Download PDFInfo
- Publication number
- JP5335241B2 JP5335241B2 JP2007555158A JP2007555158A JP5335241B2 JP 5335241 B2 JP5335241 B2 JP 5335241B2 JP 2007555158 A JP2007555158 A JP 2007555158A JP 2007555158 A JP2007555158 A JP 2007555158A JP 5335241 B2 JP5335241 B2 JP 5335241B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- hexapeptide
- kfkwpw
- peptide
- activity
- 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
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract description 32
- 241000894006 Bacteria Species 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 208000015181 infectious disease Diseases 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims description 54
- 239000003814 drug Substances 0.000 claims description 20
- 150000002632 lipids Chemical class 0.000 claims description 20
- 239000004599 antimicrobial Substances 0.000 claims description 18
- 230000000813 microbial effect Effects 0.000 claims description 12
- 241000233866 Fungi Species 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 6
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 6
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 claims description 6
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 4
- AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 claims description 3
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 3
- 239000005639 Lauric acid Substances 0.000 claims description 3
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 3
- YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 claims description 3
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 3
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003473 lipid group Chemical group 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 23
- 230000000843 anti-fungal effect Effects 0.000 abstract description 12
- 241000222122 Candida albicans Species 0.000 abstract description 11
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 abstract description 10
- 125000003118 aryl group Chemical group 0.000 abstract description 10
- 229940095731 candida albicans Drugs 0.000 abstract description 9
- 244000052769 pathogen Species 0.000 abstract description 9
- 241001045770 Trichophyton mentagrophytes Species 0.000 abstract description 8
- 241000124008 Mammalia Species 0.000 abstract description 7
- 244000053095 fungal pathogen Species 0.000 abstract description 7
- 241001480043 Arthrodermataceae Species 0.000 abstract description 5
- 241000223229 Trichophyton rubrum Species 0.000 abstract description 5
- 125000001931 aliphatic group Chemical group 0.000 abstract description 5
- 230000037304 dermatophytes Effects 0.000 abstract description 5
- 125000001165 hydrophobic group Chemical group 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 5
- 230000001988 toxicity Effects 0.000 abstract description 5
- 244000045947 parasite Species 0.000 abstract description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 138
- 230000000694 effects Effects 0.000 description 69
- 102000004196 processed proteins & peptides Human genes 0.000 description 63
- 238000000034 method Methods 0.000 description 51
- 235000001014 amino acid Nutrition 0.000 description 48
- 229940024606 amino acid Drugs 0.000 description 47
- 150000001413 amino acids Chemical class 0.000 description 44
- 206010052428 Wound Diseases 0.000 description 33
- 208000027418 Wounds and injury Diseases 0.000 description 33
- 238000012360 testing method Methods 0.000 description 25
- 239000000243 solution Substances 0.000 description 19
- 244000005700 microbiome Species 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 16
- 210000003491 skin Anatomy 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 241000700159 Rattus Species 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 230000001580 bacterial effect Effects 0.000 description 12
- 108050004290 Cecropin Proteins 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 206010017533 Fungal infection Diseases 0.000 description 10
- 208000031888 Mycoses Diseases 0.000 description 10
- 239000006071 cream Substances 0.000 description 10
- 229940124597 therapeutic agent Drugs 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 9
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 9
- 241000196324 Embryophyta Species 0.000 description 9
- 230000002538 fungal effect Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000004005 microsphere Substances 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 238000012384 transportation and delivery Methods 0.000 description 8
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 7
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 7
- 238000007112 amidation reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000002502 liposome Substances 0.000 description 7
- 230000002101 lytic effect Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000007921 spray Substances 0.000 description 7
- 230000000475 sunscreen effect Effects 0.000 description 7
- 239000000516 sunscreening agent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 230000002195 synergetic effect Effects 0.000 description 7
- 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 6
- 208000035143 Bacterial infection Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 241000191967 Staphylococcus aureus Species 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000009435 amidation Effects 0.000 description 6
- 229940121375 antifungal agent Drugs 0.000 description 6
- 208000022362 bacterial infectious disease Diseases 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000006210 lotion Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 6
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000001356 surgical procedure Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- -1 9-fluorenylmethoxycarbonyl Chemical group 0.000 description 5
- 201000003883 Cystic fibrosis Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 108010093965 Polymyxin B Proteins 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 229960003767 alanine Drugs 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 210000000416 exudates and transudate Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 229920000024 polymyxin B Polymers 0.000 description 5
- 229960005266 polymyxin b Drugs 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 208000019802 Sexually transmitted disease Diseases 0.000 description 4
- 241000223238 Trichophyton Species 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000002054 inoculum Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 3
- PAZGBAOHGQRCBP-DDDNOICHSA-N 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC PAZGBAOHGQRCBP-DDDNOICHSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 101710120040 Antifungal peptide Proteins 0.000 description 3
- 108010050820 Antimicrobial Cationic Peptides Proteins 0.000 description 3
- 102000014133 Antimicrobial Cationic Peptides Human genes 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- 241000192125 Firmicutes Species 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108010036176 Melitten Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 108010062324 SB 37 Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108010031086 Shiva-1 Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 238000005556 structure-activity relationship Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 description 2
- YYTDJPUFAVPHQA-VKHMYHEASA-N (2s)-2-amino-3-(2,3,4,5,6-pentafluorophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=C(F)C(F)=C(F)C(F)=C1F YYTDJPUFAVPHQA-VKHMYHEASA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- AKVBCGQVQXPRLD-UHFFFAOYSA-N 2-aminooctanoic acid Chemical compound CCCCCCC(N)C(O)=O AKVBCGQVQXPRLD-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 101800002011 Amphipathic peptide Proteins 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
- 241000994678 Botryotinia squamosa Species 0.000 description 2
- 101800003223 Cecropin-A Proteins 0.000 description 2
- 229940123150 Chelating agent Drugs 0.000 description 2
- 241000186427 Cutibacterium acnes Species 0.000 description 2
- 241000588724 Escherichia coli 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
- 239000007821 HATU Substances 0.000 description 2
- 108700022013 Insecta cecropin B Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 241000914716 Lenarchus rho Species 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108060003100 Magainin Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 2
- 241000083076 Neopseudocercosporella brassicae Species 0.000 description 2
- 241001670201 Peronospora destructor Species 0.000 description 2
- 229920001244 Poly(D,L-lactide) Polymers 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241001291154 Pyrenopeziza brassicae Species 0.000 description 2
- 241000269435 Rana <genus> Species 0.000 description 2
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 206010041925 Staphylococcal infections Diseases 0.000 description 2
- 241000282887 Suidae 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
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229930002945 all-trans-retinaldehyde Natural products 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 239000000058 anti acne agent Substances 0.000 description 2
- 229940124340 antiacne agent Drugs 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- HCQPHKMLKXOJSR-IRCPFGJUSA-N cecropin-a Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(N)=O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CCCCN)C1=CC=CC=C1 HCQPHKMLKXOJSR-IRCPFGJUSA-N 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000012459 cleaning agent Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 description 2
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000007388 punch biopsy Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 210000002374 sebum Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 206010040872 skin infection Diseases 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000013223 sprague-dawley female rat Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000012385 systemic delivery Methods 0.000 description 2
- BWMISRWJRUSYEX-SZKNIZGXSA-N terbinafine hydrochloride Chemical compound Cl.C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 BWMISRWJRUSYEX-SZKNIZGXSA-N 0.000 description 2
- 201000004647 tinea pedis Diseases 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical group CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 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
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 2
- CRDAMVZIKSXKFV-FBXUGWQNSA-N (2-cis,6-cis)-farnesol Chemical compound CC(C)=CCC\C(C)=C/CC\C(C)=C/CO CRDAMVZIKSXKFV-FBXUGWQNSA-N 0.000 description 1
- 239000000260 (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol Substances 0.000 description 1
- HKUAWRVNDCVEHT-NSHDSACASA-N (2s)-2-(pyren-4-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC3=CC=CC4=CC=C1C2=C34 HKUAWRVNDCVEHT-NSHDSACASA-N 0.000 description 1
- VOIZSAUUYAGTMS-LURJTMIESA-N (2s)-2-amino-3-thiophen-3-ylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC=1C=CSC=1 VOIZSAUUYAGTMS-LURJTMIESA-N 0.000 description 1
- NSOITZIGPJTCMQ-KCXFZFQESA-N (4r,7s,10s,13s,16s,19s,22r)-22-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-6-amino-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[2-[[(2s)-2-[[(2s)-2-amino-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]acetyl]amino]-4-methylpentanoyl]a Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC1)C(O)=O)[C@@H](C)O)C(C)C)=O)C1=CC=CC=C1 NSOITZIGPJTCMQ-KCXFZFQESA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- ZZUYEGMKIIREEE-UHFFFAOYSA-N 2,2,2-trifluoroethanol;hydrate Chemical compound O.OCC(F)(F)F ZZUYEGMKIIREEE-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- FZTIWOBQQYPTCJ-UHFFFAOYSA-N 4-[4-(4-carboxyphenyl)phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(O)=O)C=C1 FZTIWOBQQYPTCJ-UHFFFAOYSA-N 0.000 description 1
- UQXNEWQGGVUVQA-UHFFFAOYSA-N 8-aminooctanoic acid Chemical compound NCCCCCCCC(O)=O UQXNEWQGGVUVQA-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 241000256118 Aedes aegypti Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 241000589567 Brucella abortus Species 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- 244000197813 Camelina sativa Species 0.000 description 1
- 241000222178 Candida tropicalis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 208000035484 Cellulite Diseases 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 241000222199 Colletotrichum Species 0.000 description 1
- 241001120669 Colletotrichum lindemuthianum Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical group 0.000 description 1
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 1
- 239000000253 Denture Cleanser Substances 0.000 description 1
- 208000007163 Dermatomycoses Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 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 1
- 241001480035 Epidermophyton Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 241000287828 Gallus gallus Species 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
- 239000004471 Glycine Substances 0.000 description 1
- 108700032080 Hyalophora cecropia cecropin D Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 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 1
- 208000032376 Lung infection Diseases 0.000 description 1
- 241001480037 Microsporum Species 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- NVNLLIYOARQCIX-MSHCCFNRSA-N Nisin Chemical compound N1C(=O)[C@@H](CC(C)C)NC(=O)C(=C)NC(=O)[C@@H]([C@H](C)CC)NC(=O)[C@@H](NC(=O)C(=C/C)/NC(=O)[C@H](N)[C@H](C)CC)CSC[C@@H]1C(=O)N[C@@H]1C(=O)N2CCC[C@@H]2C(=O)NCC(=O)N[C@@H](C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(NCC(=O)N[C@H](C)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCSC)C(=O)NCC(=O)N[C@H](CS[C@@H]2C)C(=O)N[C@H](CC(N)=O)C(=O)N[C@H](CCSC)C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(N[C@H](C)C(=O)N[C@@H]3C(=O)N[C@@H](C(N[C@H](CC=4NC=NC=4)C(=O)N[C@H](CS[C@@H]3C)C(=O)N[C@H](CO)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H](CC=3NC=NC=3)C(=O)N[C@H](C(C)C)C(=O)NC(=C)C(=O)N[C@H](CCCCN)C(O)=O)=O)CS[C@@H]2C)=O)=O)CS[C@@H]1C NVNLLIYOARQCIX-MSHCCFNRSA-N 0.000 description 1
- 108010053775 Nisin Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 241000736122 Parastagonospora nodorum Species 0.000 description 1
- 206010049752 Peau d'orange Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 241000233629 Phytophthora parasitica Species 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 241000269908 Platichthys flesus Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101710166868 Sarcotoxin-1B Proteins 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000555028 Sternidius alpha Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 206010062910 Vascular infections Diseases 0.000 description 1
- 241000544286 Vibrio anguillarum Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- 239000004164 Wax ester Substances 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- 101500009721 Xenopus laevis Magainin-2 Proteins 0.000 description 1
- 241001360088 Zymoseptoria tritici Species 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000002313 adhesive film Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 208000009736 adult acne Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 1
- 229960005193 avobenzone Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- WTOFYLAWDLQMBZ-LURJTMIESA-N beta(2-thienyl)alanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CS1 WTOFYLAWDLQMBZ-LURJTMIESA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229940056450 brucella abortus Drugs 0.000 description 1
- 108010025307 buforin II Proteins 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 108010007004 cathelin Proteins 0.000 description 1
- 108010046237 cecropin P1-LI Proteins 0.000 description 1
- PRIVBYDFWSFUFP-RJLJEYQFSA-N cecropin p1 Chemical compound O=C([C@H](CCC(N)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PRIVBYDFWSFUFP-RJLJEYQFSA-N 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- UKVZSPHYQJNTOU-IVBHRGSNSA-N chembl1240717 Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)[C@H](C)O)CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=CC=C1 UKVZSPHYQJNTOU-IVBHRGSNSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 229960004022 clotrimazole Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 244000000037 crop pathogen Species 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 108090000454 dermaseptin Proteins 0.000 description 1
- YFHLIDBAPTWLGU-CTKMSOPVSA-N dermaseptin Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)N)[C@@H](C)O)[C@@H](C)O)C1=CN=CN1 YFHLIDBAPTWLGU-CTKMSOPVSA-N 0.000 description 1
- 229940049701 dermaseptin Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- HEAHZSUCFKFERC-UHFFFAOYSA-N ecamsule Chemical compound CC1(C)C2CCC1(CS(O)(=O)=O)C(=O)C2=CC(C=C1)=CC=C1C=C1C(=O)C2(CS(O)(=O)=O)CCC1C2(C)C HEAHZSUCFKFERC-UHFFFAOYSA-N 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229940043259 farnesol Drugs 0.000 description 1
- 229930002886 farnesol Natural products 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 244000000004 fungal plant pathogen Species 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 244000000061 hemibiotrophic pathogen Species 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 230000015784 hyperosmotic salinity response Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- USSYUMHVHQSYNA-SLDJZXPVSA-N indolicidin Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)CC1=CNC2=CC=CC=C12 USSYUMHVHQSYNA-SLDJZXPVSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000003410 keratolytic agent Substances 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- MGIUUAHJVPPFEV-ABXDCCGRSA-N magainin ii Chemical compound C([C@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O)C1=CC=CC=C1 MGIUUAHJVPPFEV-ABXDCCGRSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 229960000210 nalidixic acid Drugs 0.000 description 1
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 1
- OFYAYGJCPXRNBL-LBPRGKRZSA-N naphthalen-2-yl-3-alanine Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CC=CC2=C1 OFYAYGJCPXRNBL-LBPRGKRZSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000000627 niacin group Chemical class 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000004309 nisin Substances 0.000 description 1
- 235000010297 nisin Nutrition 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 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
- 229960001679 octinoxate Drugs 0.000 description 1
- 229960003921 octisalate Drugs 0.000 description 1
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical group C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 1
- 229960000601 octocrylene Drugs 0.000 description 1
- WCJLCOAEJIHPCW-UHFFFAOYSA-N octyl 2-hydroxybenzoate Chemical compound CCCCCCCCOC(=O)C1=CC=CC=C1O WCJLCOAEJIHPCW-UHFFFAOYSA-N 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000002994 phenylalanines Chemical class 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- CGIHFIDULQUVJG-UHFFFAOYSA-N phytantriol Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)(O)C(O)CO CGIHFIDULQUVJG-UHFFFAOYSA-N 0.000 description 1
- CGIHFIDULQUVJG-VNTMZGSJSA-N phytantriol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCC[C@@](C)(O)[C@H](O)CO CGIHFIDULQUVJG-VNTMZGSJSA-N 0.000 description 1
- 230000003032 phytopathogenic effect Effects 0.000 description 1
- 244000000003 plant pathogen Species 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 108010047804 ranalexin Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000020945 retinal Nutrition 0.000 description 1
- 239000011604 retinal Substances 0.000 description 1
- NCYCYZXNIZJOKI-OVSJKPMPSA-N retinal group Chemical group C\C(=C/C=O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002884 skin cream Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000012533 structure-function relationship study Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 239000006150 trypticase soy agar Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 108010026996 vishnu Proteins 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 235000019386 wax ester Nutrition 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- 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
-
- 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
- A61P31/10—Antimycotics
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicinal Preparation (AREA)
Description
本発明は、望ましい生物学的特性を有する抗微生物ヘキサペプチドを含む組成物及び方法に関する。より具体的には、ヘキサペプチドは望ましい抗真菌活性及び選択的に抗細菌活性を有する。具体的には、本発明のヘキサペプチドは、1位及び3位に電荷(親水性)残基を有し、2位、4位及び6位に疎水性残基を有し、5位にナフチルアラニン、脂肪族(例えば、プロリン)又は芳香族(フェニルアラニン)残基を有しており、一般的には式XBXBOBによって表される。これらペプチドのうちの幾つかのN末端に脂質部を加えることにより、特に血清では、活性のさらなる向上が達成されることができる。また、C末端でのアミド化は、活性を増大させると考えられる。
研究者達が、抗微生物治療及び抗微生物製剤の開発を始めてから、もう何十年にもなる。最近では、益々増加する薬剤耐性の細菌感染、ウイルス感染及び真菌感染を治療するための新規な抗微生物製剤が必要とされている。
本発明は、ヘキサペプチド構造が式XBXBOBで表され、1位及び3位に親水性荷電残基(X)、2位、4位及び6位に疎水性残基(B)、並びに、5位にナフチルアラニン、脂肪族又は芳香族残基(O)を有する抗微生物ヘキサペプチドを提供するものである。
以下のアミノ酸配列表は、本願明細書の一部を構成し、本発明の幾つかの態様をさらに示すために含められる。本発明は、これら配列のうちの1又は複数の配列図及び以下の具体的実施例の詳細な記述を参照することにより、より良く理解されるであろう。
OCTは、標準のペプチド化学を用い、アミド結合によるペプチドへのオクタン酸の付加を示す。COOHは、C−末端がアミド化されていないことを示す。Jは、フッ素化フェニルアラニンの記号である。Uは、1−Nal−OHを意味し、Zは、2−Nal−OHを意味し、ここで、Nalは、ナフチルアラニンであり、非天然アミノ酸は、フェニルアラニン及びアラニンのアナログである。上記の脂質は、OCTに対して同様に結合されており、省略文字の意味は次の通りである:myr=ミリスチン酸、und=ウンデカン酸、pen=ペンタデカン酸、pal=パルミチン酸、ste=ステアリン酸、lau=ラウリン酸、tri=トリデカン酸、cap=カプロン酸、ole=オレイン酸、non=ノナン酸、hep=ヘプタン酸、aca=8−アミノカプリル酸、deca=デカン酸である。アミノ酸の小文字はD型残基を表す。
全てのヘキサペプチドの合成は、標準のFmoc(9−フルオレニルメトキシカルボニル)を使用し、Advanced ChemTech社のApex 396マルチペプチド合成装置で行なった。Apex 396には、0.15mmolのスケールで最大40ペプチドを同時に生成するために、40ウエルの反応ブロックが設けられている。ペプチドは、標準アミノ酸を使用し、アミド化配列又は遊離酸配列のどちらかの配列として調製されることができる。レジンは、最初に洗浄し、N,N−ジメチルホルムアミド(DMF)で予め膨潤した(pre-swelled)。膨潤時間は、Rinkアミド又はWangレジンの場合で3分〜1時間である。Fmoc保護基の除去は、25%ピペリジンを含むDMF中で25分間かけて行なった。次にレジンを十分に洗浄して、微量のピペリジンを除去した。Fmocアミノ酸モノマーは、HOAt又はHOBtの等モルDMF溶液中で、予め活性化させた。溶液の濃度は、0.5Mであった。ヒンダード塩基(hindered base)(ジイソプロピルエチルアミン)を用いた塩基条件下で、活性剤としてのHATU PyBop又はHBTUと、2.5〜5倍モル量のアミノ酸を使用して、アミド結合を行なわせた。1〜1.5時間の結合の後、洗浄を行ない、再結合させて、二重又は三重結合を行なった後、成長ペプチド鎖の脱保護及び継続を行なった。結合効率は、標準カイザーテスト(standard Kaiser test)を使って監視した。レジンでのペプチド合成が一旦完了すると、前述の如く、最終Fmoc保護基が取り除かれ、残された配列は遊離塩基であった。上述の如く標準のペプチド化学反応を使用して、脂質を、有機酸としてN末端又は側鎖アミンに結合させた。
所望の抗微生物活性が保持される限り、ヘキサペプチドに対する様々な修飾が可能である。ヘキサペプチドの固有抗微生物効力を増進させるために、幾つかの修飾を用いられることができる。その他の修飾によってヘキサペプチドの取扱いを容易にすることもできる。ペプチド官能基の代表的な修飾例として、ヒドロキシル、アミノ、グアニジン、カルボキシル、アミド、フェノール、イミダゾール環又はスルフヒドリルが挙げられる。これら官能基の典型的な反応には、限定されるものではないが、ハロゲン化アルキルによるヒドロキシル基のアセチル化がある。カルボキシル基はエステル化され、アミド化され又はアルコールに還元されることできる。カルボキシル基のアミド化を触媒するのに、カルボジイミド又は他の触媒を用いることができる。アスパラギン又はグルタミンのアミド基は酸性又は塩基性条件のもとで脱アミド化されることができる。アミノ基(例えば、ペプチドの第1級アミノ基又はリジン残基のアミノ基)とのアシル化、アルキル化、アリール化又はアミド化反応は容易に起こる。チロシンのフェノール基はハロゲン化又はニトロ化されることができる。ペプチドの溶解度が低下する例として、荷電リジン基のアクリル化、又はアスパラギン酸若しくはグルタミン酸のカルボキシル基のアセチル化が含まれる。
一緒に用いられる特定のペプチド組成物が選択されると、溶液又は固相において大量(最大60kg)のペプチド合成が行われる。この合成では、保護基及び凝縮方法を注意深く選択する必要がある。全ての出発物質及び薬剤は、Sigma-Aldrich, Inc.などの化学品サプライヤーから高純度のものを入手することができる。また、アミノ酸は、Bechem又はNovabiochem(登録商標)などのサプライヤーから入手することができる。結合条件下でのアミノ酸ビルディングブロックのラセミ化は、HOBt、HOAt、HBTU又はHATUなどの次世代新薬の使用によって大いに抑制又は除去されることができる。現在は、固相方法でさえも、少なくとも10kg/batchの倍数で医薬ペプチドを製造することができる方法が開発されている。
溶液相の合成は、ラセミ化を最小限にするための基の保護、フラグメントの選択及びフラグメントの結合に関する計画を容易にする。中間体は、結晶化技術によって簡単に単離されることができることがあり、この場合、カラム・クロマトグラフィによる精製は不要であるので、大量生産(scale-up)能力を向上させる。同時製造されるフラグメントの品質は各工程で容易に制御されるできる。
固相合成には、より高分子のポリマーが用いられるが、通常、そのコストは高い。支持体の中には、大量に(in bulk)入手できないものがある。しかしながら、これらの特性は、アンカリングされたペプチドの可触性(accessibilty)と、十分な保護、脱保護又は修飾された形態のレジンからのペプチドの遊離において重要な役割を果たす。固相ペプチドの合成(SPPS)を実験室規模から製造規模へ移行させることは、合成プロセス全体の自動化が容易であり、合成工程の効率を監視及び最適化できる点において明らかに有利である。生産規模の活性化プロセスは広く知られており、環境的に無害である。また、SPPSでは、生産規模で廃棄濾液から過剰のアミノ酸ビルディングブロックを直接回収及びリサイクルすることができる。
ミクロスフェアの調製は、カプセル化されるペプチド組成物の親水性又は疎水性に応じて、様々な方法が用いられる[Wang, H. T., et al. 1991, "Influence of formulation methods on the in vitro controlled release of protein from poly(ester) microspheres," J. of Controlled Release 17:23-25]。この文献中、この明細書に記載されていない方法及び材料については、本願へ組み込まれるものとする。
本発明の更なる実施例は、上記ヘキサペプチドを使用する方法に関するものである。使用方法は、感染していない正常な哺乳類細胞を傷つけたり殺したりしないことが好ましい。治療量レベルでの使用方法は、感染していない正常な哺乳類細胞を傷つけたり殺したりしないことが好ましい。使用方法は、単一のヘキサペプチドの使用に関するものでもよいし、複数のヘキサペプチドの使用に関するものでもよい。
本発明はまた、様々な哺乳類の感染症の治療に用いられることが考えられる。次の表4は、本発明の組成物及び方法の対象となる哺乳類(動物及びヒトを含む)の様々な真菌症を示している。細菌感染及び/又は真菌感染の治療に有用な医薬組成物は、本発明によってもたらされる。この医薬組成物は、有効量の抗微生物薬剤と医薬的に許容できるキャリアとを含んでいる。ここに列挙した病原有機物の幾つかについて、この明細書に詳細に記載したヘキサペプチド組成物を用いて試験を行なった。医薬的に許容されるキャリアは、当該分野で知られており、該キャリアの中に本発明のヘキサペプチドが含められ、送達されることができる[The Pharmacopeia of the United States and the National Formulary]。
本発明のさらなる実施例は、治療剤の活性を付加的又は相乗的に向上させる方法に関する。この方法は、本発明の少なくとも1種のヘキサペプチドと治療剤(例えば、ペニシリン等の抗生物質)を含む組成物を調製することを含んでいる。或いはまた、この方法では、ヘキサペプチド(又はヘキサペプチドの複合物)による治療は、他の治療剤と共に用いることを含んでいる。ヘキサペプチド又はヘキサペプチドの複合物は、表1に示されるヘキサペプチドのどれであってもよい。本発明の方法で好適に投与されるヘキサペプチドは、SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:62、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:72、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:83及びSEQ ID NO:84のうちの少なくとも1種である。
NCCLS(National Committe for Clinical Laboratory Standards)の前記液体微量希釈法の少し改変されたバージョンを用いて、当該ヘキサペプチドのMICs(最小発育阻止濃度)を求めた[Steinberg et al., AAC 41: 1738, 1997]。簡単に説明すると、最も適当な溶媒中に、10X濃度の抗微生物剤を調製した。ヘキサペプチドについては、0.2%のウシ血清アルブミンを含む0.01%の酢酸をキャリアタンパク質として用いた。BAPからのコロニーを媒体の中で再懸濁させ、懸濁液を0.5マクファーランド標準と一致するように調節して、接種材料を調製した。懸濁液は、新鮮培地の中で希釈し(微生物に対するNCCLS推奨)、細菌は2×105〜7×105CFU/ml、カンジダ菌は2×103〜7×103CFU/mlとなるようにした。96ウェルのポリプロピレンマイクロタイタープレートの各ウェルに100μlアリコートの微生物懸濁液を調合した後、11μlの試験化合物を加えた。MICは、35℃で16〜20時間後(細菌)又は46〜50時間後(カンジダ)に、目に見える濁りを防止できる薬剤の最低濃度として規定される。
リポタイコ酸(LTA)は、黄色ブドウ球菌及びニキビ桿菌(P.acnes)等の微生物を含むグラム陽性細菌の一般的な細胞壁成分である。感染中はLTAを放出するので、宿主炎症反応の伝達物質を放出し、その結果、敗血症(敗血症ショック)を引き起こすことがある。例えば、動物に注入すると、LTAは、敗血症ショックの多くの特徴を引き出す。これら特徴には、サイトカイン産生、白血球減少、循環障害、多臓器不全症候群及び死亡が含まれる。カチオン性ペプチド(長さ26−29残基)によるLTAの結合により、LTAの能力が低下し、細胞が炎症反応に変化することがスコットらにより立証されている[Scott et al.(Infect. And Immun. 67: 6445-6453 (1999))]。図7に示されているように、ヘキサペプチドは、(1) LTA(SEQ ID NO:55)と結合しないペプチドと、(2) LTA(SEQ ID NO:72)と結合するペプチドの2種類に分けられることができる。スコットらが記載したLTA結合アッセイ[Infect. And Immun. 67: 6445-6453 (1999)]を使用し、SEQ ID NO:72が、代表的な高電荷アルファヘリックス両媒性ペプチド(例えば、P50(VAKKLAKLAKKLAKLAL-NH2))と同程度までLTAを結合することを示している(図7)。そのような短いペプチドでは予期されなかったことで、ヘキサペプチドの種類によっては、治療価値がもたらされる。これに対し、SEQ ID NO:83及びSEQ ID NO:55はLTAを結合しない(図7)。
短い生理活性ペプチドは、例えばニキビのような皮膚症状への適用を非常に期待することができる。リポ−ヘキサペプチドの活性が、ニキビ桿菌の菌株の全体に一定であるかどうか及びその活性が従来のより長い抗微生物ペプチドと同等かどうかを調べるために、有機物10株(ATCC株)について、SEQ ID NO:72、SEQ ID NO:55及びSEQ ID NO:81に対する抗作用を試験し、P50と比較した。結果は同等か、又は長い高電荷ペプチドよりも良好なものもあった(表11)。
<A.XBXBOBヘキサペプチド>
抗真菌活性を示すヘキサペプチドは、上記式に従う。なお、上記式中、Xは荷電(親水性)、Oはある範囲の残基であるが、ナフチルアラニン、脂肪族残基(プロリンなど)又は芳香族残基(フェニルアラニンなど)が好ましく、Bは疎水性残基である。更に、C−末端のアミド化は活性を向上させるので、場合によっては、前記アミド化が活性化のために必要とされる。そのようなヘキサペプチドの代表例は次のとおりである。
SEQ ID NO:1: KFKWPW*** 最も活性
SEQ ID NO:2: KWRWPW** 活性
SEQ ID NO:3: KWKWFW* 活性
図1に示されるように、モデルJ-810分光偏光計(Jasco)に記録されたCDスペクトルは、経路1mmの水晶セルを使用し、室温で50nm/分のスキャン速度にて、190〜250nmの範囲を1試料につき合計10回スキャンして得られたものである。記録されたスペクトルは、次の3種類の環境下で、100μg/mlのペプチド濃度で測定したものであり、前記環境は、pH7.5の10mMトリス緩衝液と、50%TFE−水と、POPC:POPG(1:1 w:w,2mM)のリポソームである。どの場合も、得られたペプチドスペクトルは、ペプチドがない状態で、溶液成分のスペクトルを差し引いている。
抗微生物ペプチドのアシル化により、それらの活性が向上することはこれまでにも明らかにされている。活性の向上は、コアペプチド、結合した脂質の長さ、また場合によっては結合した脂質の種類に依存する[Radzishevsky et al(Antimicrob. Agents Chemother. 49: 2412-2420 (2005))]。コアペプチドSEQ ID NO:1を得るに当り、長さが炭素数6〜18の範囲で、アミノアシル基アミノカプリル酸を含む脂質を結合させた。結合は、標準のペプチド化学法により行なった。表14に示されるように、抗微生物活性に関して、結合した脂質の最適長さは、炭素数が8〜14であった。しかしながら、Radzishevskyらが記載したように修飾されたペプチド[Antimicrob. Agents Chemother. 49: 2412-2420 (2005)]とは異なり、SEQ ID NO:76の場合は、アミノカプリル酸などのアミノアシル基を加えても、活性の向上は認められなかったことは留意されるべきである。
抗微生物ペプチドの従来の作用メカニズムは、細胞膜の崩壊能力であった。ヘキサペプチド及びリポヘキサペプチドが、細菌又はヒト細胞を模擬した脂質から成る脂質膜と相互作用する能力について、代表的なペプチドSEQ ID NO:1(P0666)及びSEQ ID NO:55(P1032)を用いて調べた。これらの試験では 従来の抗微生物ペプチド(アミノ酸長さ15-40)は、二層膜の破壊によって細胞質に漏れが生じ、細胞死に至らしめる。ヘキサペプチドP1032及び脂質化アナログP1032が同じような作用メカニズムを有するかどうかを調べるのに、diSC35蛍光デクエンチング法を用いた。diSC35は、膜電位感受性色素であり、細胞膜の膜電位勾配及び濃度によって活性化された細胞(energized cells)に含まれており、色素蛍光のクエンチングが起こる。膜電位が壊れると、色素が解放され、もはやクエンチされなくなり、蛍光が増加する。ここでは、生きた黄色ブドウ球菌細胞が標的有機物として用いられた。各ペプチドは細胞質膜電位を脱分極する能力を有しており、これにより、diSC35は細胞から緩衝液に放出され、これに対応して増加する蛍光が測定される。P50(VAKKLAKLAKKLAKLAL-NH2)とは異なり、膜を破壊する従来のペプチドは、P0666又はP1032はどちらも、黄色ブドウ球菌の細胞膜への浸透を生じさせることができなかった。
新規な作用メカニズムに関しては、抵抗の発現が常に懸念される。MRSA(株SAP0017)及び黄色ブドウ球菌(株ATCC 21923)を、MICの半分濃度のP1032及びP1032dの存在下で、毎日、連続的に供給した。30連続通過後、MICの変化は、開始時のMICの2倍希釈の範囲内であった。ペプチドが不存在のとき、各抵抗性株が1回するだけで元のMICに戻る結果となったから、このような抵抗は過渡的順応(transient adaptation)であることが立証された。
SEQ ID NO:1(P0666)を含む様々なヘキサペプチドの活性を比較するため、皮膚真菌トリコフィトン・ルブルム及びトリコフィトン・メンタグロフィテスに対するMICを測定した。調べた試料の濃度は、それぞれ、2000μg/ml、1000μg/ml、500μg/ml、250μg/ml及び125μg/mlであった。使用した培地は、寒天を含まない修飾サブロー培地(modified Sabouraud medium)である。修飾サブロー培地100mLを得るのに、サブローデキストロースブロス(Difco)3gを、100mLの脱イオン水の中に混合した。pHは、0.1NのNaOHにより7.0に調節した。溶液は、30分間、高圧釜で蒸気殺菌した。940μLの培地を、プラスチックキャップ付きの20mL容量の滅菌試験管の中に注いで、冷却した。
本発明のヘキサペプチドの全身投与の潜在的毒性効果を評価するために、抗真菌活性を示すペプチドを、マウスの尾への静脈注射(投与量20mg/kg)によりマウスの血液系へ導入した。表13のデータに示されるように、SEQ ID NO:1(Ref. P0666; KFKWPW-NH2)は、他の供試ペプチドとは異なり、全身毒性は認められなかった。
[1]P1032のインビボ活性
濃度0.1mg/ml及び0.5mg/mlのSEQ ID NO:55(S35-2)の試料について、細胞毒性試験(試験時間24時間及び48時間)を行ない、細胞の密集度、円鋸歯状形成、空胞変性及び細胞融解を評価し、毒性のないことが確認された。
I.HEC4%の溶液に含まれるP-50ペプチド1%、及び
II.HEC4%のジェルに含まれるSEQ ID NO:55(P-1032)が1%のペプチド
ドレッシングを交換する毎に、各創傷を観察し、傷の表面及び組織反応を評価した。チェックした傷の状態は、次の5項目である。
i.創傷フィルムの状態: 傷を覆うのに用いた接着フィルムは、傷周囲の皮膚にまだ完全に接着しているか?
ii.傷表面: 傷表面の外観はどうなったか?
iii.浸出物(exudate)の量: フィルムの下にトラップされた浸出物の量は? 多くの場合、浸出物が蓄積されると接着性が損なわれるため、浸出物が漏出する。
iv.組織反応の重症度: 組織反応の程度を、1(小さい)、2(中程度)、3(大きい)の3段階で評価した。
v.影響を受けた組織の%: 傷表面に、変性して脆弱な組織が含まれる場合、ガーゼを押圧することによって傷表面をぬぐい取れることがある。この試験により、変性組織と粘性浸出物との区別をより良好に行なうことができる。
手術から72時間後に、ラットを、安楽死させて、ドレッシングを取り除き、パンチ生検を行なうために、皮下組織に達する直径8mmの創傷を、創傷の中央部から切り取った。予め検量されたチューブの中には5mlの生理食塩水が入れられており、該チューブの中に生検試料を入れた。試料が入れられたチューブを再検量し、試料重量を求めた。生検試料を均質化した後、4倍に希釈し、トリプチケースソイ寒天平板培地を作った。平板を一晩培養し、コロニーを計数し、組織1グラム当たりの細菌数を算出した。得られた細菌数は、10を底とする対数に変換した。各グループの平均及び標準偏差を計算し、ANOVA(Analysis of Variance(分散分析))を用いて、3つの治療グループにどんな有意な相違があるかを調べた。
試験中、全てのラットは、合併症を起こすことなく生存した。
処置した12の傷のうち、11の傷の中に細菌は検出されなかった(表17及び18)。1%P-50で処置を施した傷に、黄色ブドウ球菌が少し検出された(表18)。
一般的には、ペプチドSEQ ID NO:55 ( P-1032)に対する組織の反応は、軽度であったが、P-50に対する反応は、軽度乃至中程度であった(表19の結果を参照)。
4%HEC中での1%SEQ ID NO:55 (P-1032)の黄色ブドウ球菌(ATCC12600)に対する抗微生物作用は、1%P-50と同程度であった(表17−18)。
Claims (12)
- KFKWPW-NH2(SEQ ID NO:1)、OCT-KFKWPW-NH2(SEQ ID NO:55)、OCT-KWKWFW-NH2(SEQ ID NO:56)、KWKWUW-NH2(SEQ ID NO:62)、及びKWKWZW-NH2(SEQ ID NO:63)からなる群から選択される配列(Uは、1-Nal-OHを意味し、Zは、2-Nal-OHを意味する。)で表される、抗微生物ヘキサペプチド。
- ヘキサペプチドはSEQ ID NO:1である請求項1のヘキサペプチド。
- ヘキサペプチドは脂質で修飾されている請求項1のヘキサペプチド。
- 脂質はヘプタン酸、ノナン酸、ラウリン酸、ミリスチン酸、デカン酸、ペンタデカン酸、ウンデカン酸、トリデカン酸及びオクタン酸からなる群から選択される請求項3のヘキサペプチド。
- ヘキサペプチドは、Non-KFKWPW-NH2(SEQ ID NO:70)、Lau-KFKWPW-NH2(SEQ ID NO:72)、Myr-KFKWPW-NH2(SEQ ID NO:77)、Pen-KFKWPW-NH2(SEQ ID NO:78)、Und-KFKWPW-NH2(SEQ ID NO:79)、Tri-KFKWPW-NH2(SEQ ID NO:80)、Oct-kfkwpw-NH2(SEQ ID NO:81)、Lau-kfkwpw-NH2(SEQ ID NO:83)、及びDeca-KFKWPW-NH2(SEQ ID NO:85)からなる群(SEQ ID NO:81及びSEQ ID NO:83のアミノ酸の小文字はD型残基を表す。)から選択される請求項4のヘキサペプチド。
- ヘキサペプチドはSEQ ID NO:72である請求項5のヘキサペプチド。
- ヘキサペプチドはSEQ ID NO:79である請求項5のヘキサペプチド。
- ヘキサペプチドはSEQ ID NO:85である請求項5のヘキサペプチド。
- 薬剤として用いられる請求項1乃至8の何れかに記載のヘキサペプチド。
- 細菌又は真菌によって引き起こされる微生物感染の治療又は予防に用いられる請求項1乃至8の何れかに記載のヘキサペプチド。
- 請求項1乃至8の何れかに記載のヘキサペプチドと、医薬的に許容されるキャリアとを含む組成物。
- ヘキサペプチドは水溶液に可溶である請求項11の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65127005P | 2005-02-09 | 2005-02-09 | |
US60/651,270 | 2005-02-09 | ||
PCT/US2006/004147 WO2006086321A2 (en) | 2005-02-09 | 2006-02-07 | Antimicrobial hexapeptides |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2008537537A JP2008537537A (ja) | 2008-09-18 |
JP2008537537A5 JP2008537537A5 (ja) | 2009-04-02 |
JP5335241B2 true JP5335241B2 (ja) | 2013-11-06 |
Family
ID=36793611
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007555158A Active JP5335241B2 (ja) | 2005-02-09 | 2006-02-07 | 抗微生物ヘキサペプチド |
Country Status (13)
Country | Link |
---|---|
US (1) | US7407940B2 (ja) |
EP (1) | EP1853620B1 (ja) |
JP (1) | JP5335241B2 (ja) |
KR (1) | KR101306643B1 (ja) |
CN (1) | CN101155825B (ja) |
AT (1) | ATE540969T1 (ja) |
AU (1) | AU2006212922B2 (ja) |
CA (1) | CA2597191C (ja) |
DK (1) | DK1853620T3 (ja) |
ES (1) | ES2378242T3 (ja) |
PL (1) | PL1853620T3 (ja) |
SI (1) | SI1853620T1 (ja) |
WO (1) | WO2006086321A2 (ja) |
Families Citing this family (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070207112A1 (en) * | 2005-12-07 | 2007-09-06 | Grant Industries, Inc. | Anti-acne composition |
IL172896A0 (en) * | 2005-12-29 | 2006-06-11 | Yeda Res & Dev | Cxcr4 inhibition |
US7989160B2 (en) | 2006-02-13 | 2011-08-02 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptide sequences involved in the process of bone remodeling |
US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
US7713937B2 (en) * | 2006-11-10 | 2010-05-11 | Cara Therapeutics, Inc. | Synthetic peptide amides and dimeric forms thereof |
US7842662B2 (en) | 2006-11-10 | 2010-11-30 | Cara Therapeutics, Inc. | Synthetic peptide amide dimers |
AU2007317817B2 (en) * | 2006-11-10 | 2012-09-20 | Cara Therapeutics, Inc. | Synthetic peptide amides |
US8906859B2 (en) | 2006-11-10 | 2014-12-09 | Cera Therapeutics, Inc. | Uses of kappa opioid synthetic peptide amides |
US8236766B2 (en) * | 2006-11-10 | 2012-08-07 | Cara Therapeutics, Inc. | Uses of synthetic peptide amides |
US7713927B2 (en) * | 2007-01-16 | 2010-05-11 | The Regents Of The University Of California | Antimicrobial peptides |
KR100879220B1 (ko) | 2007-11-12 | 2009-01-19 | 아주대학교산학협력단 | 식물병원성 세균에 대한 항미생물 펩티드 kcm21 |
KR100879221B1 (ko) | 2007-11-12 | 2009-01-19 | 아주대학교산학협력단 | 식물병원성 세균에 대한 항미생물 펩티드 krs22 |
GB0724951D0 (en) | 2007-12-20 | 2008-01-30 | Lytix Biopharma As | Compounds |
WO2009146885A2 (en) * | 2008-06-02 | 2009-12-10 | Spiderbiotech S.R.L. | Lipidated antibacterial peptides |
GB0818074D0 (en) * | 2008-10-02 | 2008-11-05 | Lytix Biopharma As | Treatment of biofilms |
GB0818072D0 (en) | 2008-10-02 | 2008-11-05 | Lytix Biopharma As | Compounds |
GB0918579D0 (en) * | 2009-10-22 | 2009-12-09 | Imp Innovations Ltd | Gadd45beta targeting agents |
CA2781405A1 (en) * | 2009-11-23 | 2011-05-26 | Palatin Technologies, Inc. | Melanocortin-1 receptor-specific linear peptides |
WO2013086003A1 (en) * | 2011-12-05 | 2013-06-13 | The Ohio State University | Antimicrobial agent, bacterial strain, biosynthesis, and methods of use |
EP2820150A1 (en) * | 2012-03-01 | 2015-01-07 | Novo Nordisk A/S | N-terminally modified oligopeptides and uses thereof |
ES2723885T3 (es) | 2012-07-19 | 2019-09-03 | Daiichi Sankyo Co Ltd | Anticuerpos anti-Siglec-15 |
FR3002452B1 (fr) * | 2013-02-28 | 2016-02-12 | Dermaconcept Jmc | Composition dermatologique antimicrobienne topique |
TWI577697B (zh) * | 2013-11-28 | 2017-04-11 | 國立清華大學 | 耐高鹽及抗蛋白之抗菌胜肽及其製造方法 |
KR102092831B1 (ko) | 2015-01-16 | 2020-03-24 | 가부시키가이샤 만다무 | 클렌징 로션, 시트 화장료 및 미용 방법 |
US9738684B2 (en) | 2015-06-29 | 2017-08-22 | Council Of Scientific & Industrial Research | N-terminally modified linear and branched polyamine conjugated peptidomimetics as antimicrobials agents |
KR101855170B1 (ko) * | 2015-11-18 | 2018-05-08 | (주)노바셀테크놀로지 | 신규 항균 펩타이드 및 그의 용도 |
CN109942713A (zh) * | 2018-12-28 | 2019-06-28 | 广州医科大学 | 新型抗菌肽及其应用 |
KR102170236B1 (ko) | 2019-03-19 | 2020-10-29 | (주)노바셀테크놀로지 | 신규 다중 기능성 펩타이드 및 그의 용도 |
WO2020225255A1 (en) | 2019-05-06 | 2020-11-12 | Université De Genève | Antimicrobial tailored chitosan |
CN110950932B (zh) * | 2020-01-09 | 2023-04-18 | 福州大学 | 一种修饰肽的制备及其应用 |
KR102220323B1 (ko) * | 2020-05-15 | 2021-02-26 | (주)노바셀테크놀로지 | 신규 다중 기능성 펩타이드 및 그의 용도 |
KR102429281B1 (ko) * | 2020-05-25 | 2022-08-05 | (주)노바셀테크놀로지 | 신규 안구건조증 치료용 약학적 조성물 |
KR102486996B1 (ko) * | 2020-09-04 | 2023-01-10 | 서울대학교병원 | 펩타이드 및 이를 포함하는 피부 주름 개선용 조성물 및 대사성 질환 치료용 조성물 |
CN111925422B (zh) * | 2020-09-17 | 2021-05-18 | 张雪山 | 抗菌肽及其在制备药物或化妆品中的应用 |
CN113248572B (zh) * | 2021-04-30 | 2023-04-11 | 重庆理工大学 | 一种抗多重耐药菌环肽及其应用 |
CZ309857B6 (cs) | 2022-03-31 | 2023-12-20 | Contipro A.S. | Hexapeptid, kompozice zahrnující tento hexapeptid a jejich topické použití |
CN116332777A (zh) * | 2023-02-20 | 2023-06-27 | 华中科技大学 | 二芳基苯甲胺类化合物、制备及作为载体合成多肽的应用 |
CN116041422B (zh) * | 2023-03-31 | 2023-06-16 | 四川大学 | 自组装抗菌肽及其组合物、药物载体、载药体系和用途 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4355104A (en) | 1980-06-17 | 1982-10-19 | Kabigen Ab | Bacteriolytic proteins |
US4520016A (en) | 1980-06-17 | 1985-05-28 | Kabigen Ab | Bacteriolytic proteins |
US5861478A (en) | 1987-07-06 | 1999-01-19 | Helix Biomedix, Inc. | Lytic peptides |
CA1327311C (en) | 1987-07-06 | 1994-03-01 | Jesse M. Jaynes | Therapeutic antimicrobial polypeptides, their use and methods for preparation |
WO1989000194A1 (en) | 1987-07-06 | 1989-01-12 | Louisiana State University Agricultural And Mechan | Inhibition of eucaryotic pathogens and neoplasms and stimulation of fibroblasts and lymphocytes with lytic peptides |
EP1004595B1 (en) | 1989-04-10 | 2003-06-18 | Helix BioMedix, Inc. | Lytic and proliferative peptides and their use as pharmaceutic and phytopharmaceutic agents |
CA2107674A1 (en) | 1991-04-08 | 1992-10-09 | W. Lee Maloy | Novel peptide compositions and uses therefor |
US5561107A (en) | 1993-06-04 | 1996-10-01 | Demeter Biotechnologies, Ltd. | Method of enhancing wound healing by stimulating fibroblast and keratinocyte growth in vivo, utilizing amphipathic peptides |
US5955573A (en) | 1993-06-04 | 1999-09-21 | Demegen, Inc. | Ubiquitin-lytic peptide fusion gene constructs, protein products deriving therefrom, and methods of making and using same |
WO1994028921A1 (en) | 1993-06-04 | 1994-12-22 | Demeter Biotechnologies, Ltd. | Method of treating pulmonary disease states with non-naturally occurring amphipathic peptides |
AU1086595A (en) | 1993-11-08 | 1995-05-29 | Demeter Biotechnologies, Ltd. | Methylated lysine-rich lytic peptides and method of making same by reductive alkylation |
CA2180748A1 (en) * | 1994-01-18 | 1995-07-20 | U. Prasad Kari | Ion-channel forming amphiphilic peptides having n-terminal modifications |
US5789542A (en) | 1994-04-22 | 1998-08-04 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Amphipathic peptides |
IL114697A0 (en) | 1994-07-22 | 1995-11-27 | Demeter Biotech Ltd | Polypeptides comprising ubiquitin-lytic peptide fusion protein products deriving therefrom their preparation and use |
EP0839156A1 (en) * | 1995-07-20 | 1998-05-06 | Xoma Corporation | Anti-fungal peptides |
EP0866805A1 (en) | 1995-12-12 | 1998-09-30 | Karolinska Innovations AB | PEPTIDE BINDING THE KLVFF-SEQUENCE OF AMYLOID $g(b) |
US6566334B1 (en) | 1997-02-06 | 2003-05-20 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Short amphipathic peptides with activity against bacteria and intracellular pathogens |
US6635740B1 (en) | 1997-03-27 | 2003-10-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Ligand/lytic peptide compositions and methods of use |
CA2396422A1 (en) | 2000-01-06 | 2001-07-12 | Monsanto Technology Llc | Preparation of deallergenized proteins and permuteins |
MXPA02012249A (es) * | 2000-06-16 | 2004-01-26 | Hercules Inc | Peptidos, composiciones y metodos para el tratamiento de burkholderia cepacia. |
BR0209434A (pt) * | 2001-05-04 | 2006-02-07 | Scripps Research Inst | Peptìdeos antimicrobianos e composições |
-
2006
- 2006-02-07 CN CN200680011180.7A patent/CN101155825B/zh active Active
- 2006-02-07 KR KR1020077020308A patent/KR101306643B1/ko active IP Right Grant
- 2006-02-07 AT AT06720369T patent/ATE540969T1/de active
- 2006-02-07 PL PL06720369T patent/PL1853620T3/pl unknown
- 2006-02-07 WO PCT/US2006/004147 patent/WO2006086321A2/en active Application Filing
- 2006-02-07 CA CA2597191A patent/CA2597191C/en active Active
- 2006-02-07 AU AU2006212922A patent/AU2006212922B2/en not_active Ceased
- 2006-02-07 EP EP06720369A patent/EP1853620B1/en active Active
- 2006-02-07 JP JP2007555158A patent/JP5335241B2/ja active Active
- 2006-02-07 ES ES06720369T patent/ES2378242T3/es active Active
- 2006-02-07 SI SI200631248T patent/SI1853620T1/sl unknown
- 2006-02-07 DK DK06720369.5T patent/DK1853620T3/da active
- 2006-02-08 US US11/350,192 patent/US7407940B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US7407940B2 (en) | 2008-08-05 |
SI1853620T1 (sl) | 2012-03-30 |
KR20070107748A (ko) | 2007-11-07 |
KR101306643B1 (ko) | 2013-09-12 |
ATE540969T1 (de) | 2012-01-15 |
ES2378242T3 (es) | 2012-04-10 |
WO2006086321A2 (en) | 2006-08-17 |
EP1853620A2 (en) | 2007-11-14 |
WO2006086321A3 (en) | 2007-02-22 |
AU2006212922A1 (en) | 2006-08-17 |
US20060229252A1 (en) | 2006-10-12 |
CN101155825A (zh) | 2008-04-02 |
AU2006212922B2 (en) | 2011-04-21 |
CN101155825B (zh) | 2014-11-26 |
PL1853620T3 (pl) | 2012-07-31 |
EP1853620B1 (en) | 2012-01-11 |
DK1853620T3 (da) | 2012-03-26 |
CA2597191A1 (en) | 2006-08-17 |
JP2008537537A (ja) | 2008-09-18 |
CA2597191C (en) | 2014-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5335241B2 (ja) | 抗微生物ヘキサペプチド | |
JP5688290B2 (ja) | 抗菌性ペプチド | |
AU2007272272B2 (en) | Antimicrobial peptides | |
KR102137941B1 (ko) | 항균 펩티드 | |
JP6964577B2 (ja) | 抗菌性ペプチド及びその使用方法 | |
CA2441562C (en) | Short bioactive peptides and methods for their use | |
US20050282755A1 (en) | Compositions having antimicrobial activity and uses thereof | |
US10435437B2 (en) | Modified apidaecin derivatives as antibiotic peptides | |
André et al. | Structure–activity relationship-based optimization of small temporin-SHf analogs with potent antibacterial activity | |
WO2012145680A2 (en) | Anti-microbial peptides and uses therefore | |
WO2006127715A1 (en) | Antimicrobial peptides | |
Makhlynets et al. | Characteristics and therapeutic applications of antimicrobial peptides | |
CA2312191A1 (en) | Threonine-containing protegrins | |
JPH06511234A (ja) | C末端置換を有する生物活性ペプチド組成物および治療法 | |
Kuhn-Nentwig et al. | Cupiennin 1d*: the cytolytic activity depends on the hydrophobic N-terminus and is modulated by the polar C-terminus | |
WO2015099535A1 (en) | Thrombocidin-derived antimicrobial peptides | |
EP4284812A1 (en) | Novel selective antimicrobial fusion peptides |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090204 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090204 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110906 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111201 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120904 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121129 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130219 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130408 |
|
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: 20130723 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130731 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5335241 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |