NO333073B1 - Cytotoksiske peptider modifisert med en eller flere ikke-genetiske, voluminose og/eller lipofile aminosyrer. - Google Patents

Info

Publication number

NO333073B1

NO333073B1 NO20010995A NO20010995A NO333073B1 NO 333073 B1 NO333073 B1 NO 333073B1 NO 20010995 A NO20010995 A NO 20010995A NO 20010995 A NO20010995 A NO 20010995A NO 333073 B1 NO333073 B1 NO 333073B1

Authority

NO

Norway

Prior art keywords

peptides

peptide

lfb

amino acids

bulky

Prior art date

1998-08-28

Links

• Espacenet
• Global Dossier
• Discuss

• 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 363
• 150000001413 amino acids Chemical class 0.000 title claims abstract description 153
• 230000002068 genetic effect Effects 0.000 title claims description 51
• 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 201
• 230000001472 cytotoxic effect Effects 0.000 title abstract description 39
• 231100000433 cytotoxic Toxicity 0.000 title abstract description 25
• 125000002091 cationic group Chemical group 0.000 claims abstract description 22
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 19
• 150000002148 esters Chemical class 0.000 claims abstract description 8
• 239000003814 drug Substances 0.000 claims abstract description 7
• 150000003839 salts Chemical class 0.000 claims abstract description 6
• 150000001408 amides Chemical class 0.000 claims abstract description 3
• 229940024606 amino acid Drugs 0.000 claims description 154
• 235000001014 amino acid Nutrition 0.000 claims description 152
• 206010028980 Neoplasm Diseases 0.000 claims description 34
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 32
• 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 claims description 31
• 229960003767 alanine Drugs 0.000 claims description 24
• 235000004279 alanine Nutrition 0.000 claims description 23
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 20
• 230000003013 cytotoxicity Effects 0.000 claims description 13
• 231100000135 cytotoxicity Toxicity 0.000 claims description 13
• COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 13
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 8
• 208000035143 Bacterial infection Diseases 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 150000008574 D-amino acids Chemical class 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• PECGVEGMRUZOML-AWEZNQCLSA-N (2s)-2-amino-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C([C@H](N)C(O)=O)C1=CC=CC=C1 PECGVEGMRUZOML-AWEZNQCLSA-N 0.000 claims description 3
• MWHVBFNZTDNYRK-HNNXBMFYSA-N (2s)-2-azaniumyl-3-(7-phenylmethoxy-1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H]([NH3+])C([O-])=O)=CNC2=C1OCC1=CC=CC=C1 MWHVBFNZTDNYRK-HNNXBMFYSA-N 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 239000001257 hydrogen Substances 0.000 claims description 3
• YPJJGMCMOHDOFZ-ZETCQYMHSA-N (2s)-2-(1-benzothiophen-3-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CSC2=C1 YPJJGMCMOHDOFZ-ZETCQYMHSA-N 0.000 claims description 2
• FNQLUUASYSCLNV-AWEZNQCLSA-N (2s)-2-(cyclohexylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC1CCCCC1)C1=CC=C(O)C=C1 FNQLUUASYSCLNV-AWEZNQCLSA-N 0.000 claims description 2
• 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 claims description 2
• 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 claims description 2
• XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 claims description 2
• 229940034208 thyroxine Drugs 0.000 claims description 2
• XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 claims description 2
• VKBLQCDGTHFOLS-NSHDSACASA-N (2s)-2-(4-benzoylanilino)propanoic acid Chemical compound C1=CC(N[C@@H](C)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 VKBLQCDGTHFOLS-NSHDSACASA-N 0.000 claims 1
• WUTPXBXSEMJIDW-HNNXBMFYSA-N (2s)-2-(benzylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NCC=1C=CC=CC=1)C1=CC=C(O)C=C1 WUTPXBXSEMJIDW-HNNXBMFYSA-N 0.000 claims 1
• 230000000844 anti-bacterial effect Effects 0.000 abstract description 53
• 238000000034 method Methods 0.000 abstract description 33
• 239000003242 anti bacterial agent Substances 0.000 abstract description 10
• 239000002246 antineoplastic agent Substances 0.000 abstract description 4
• 239000008194 pharmaceutical composition Substances 0.000 abstract 1
• CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical group C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 130
• 101800004361 Lactoferricin-B Proteins 0.000 description 108
• 210000004027 cell Anatomy 0.000 description 55
• 230000000694 effects Effects 0.000 description 55
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
• 230000001965 increasing effect Effects 0.000 description 36
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
• 239000000243 solution Substances 0.000 description 33
• 229960004799 tryptophan Drugs 0.000 description 31
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
• 125000006239 protecting group Chemical group 0.000 description 29
• 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 28
• 230000004048 modification Effects 0.000 description 27
• 238000012986 modification Methods 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• 230000000259 anti-tumor effect Effects 0.000 description 26
• CFFMZOZGXDAXHP-HOKBLYKWSA-N lactoferricin Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CSSC[C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CO)C(=O)N[C@H](C(N[C@H](C(=O)N1)[C@@H](C)O)=O)[C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CFFMZOZGXDAXHP-HOKBLYKWSA-N 0.000 description 23
• 241000894006 Bacteria Species 0.000 description 22
• -1 2,2,5,7,8-pentamethylchroman-6-sulfonyl Chemical group 0.000 description 21
• 239000000203 mixture Substances 0.000 description 21
• 241000283690 Bos taurus Species 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• 241000699670 Mus sp. Species 0.000 description 18
• 230000015572 biosynthetic process Effects 0.000 description 18
• 239000000047 product Substances 0.000 description 18
• 238000006467 substitution reaction Methods 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 230000001580 bacterial effect Effects 0.000 description 17
• 210000004899 c-terminal region Anatomy 0.000 description 16
• 241000588724 Escherichia coli Species 0.000 description 15
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
• 241001529936 Murinae Species 0.000 description 15
• 230000000845 anti-microbial effect Effects 0.000 description 15
• 235000021242 lactoferrin Nutrition 0.000 description 15
• 238000002360 preparation method Methods 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 14
• 241000282414 Homo sapiens Species 0.000 description 14
• 108010063045 Lactoferrin Proteins 0.000 description 14
• 102000010445 Lactoferrin Human genes 0.000 description 14
• 150000001875 compounds Chemical class 0.000 description 14
• 239000011347 resin Substances 0.000 description 14
• 229920005989 resin Polymers 0.000 description 14
• 238000003786 synthesis reaction Methods 0.000 description 14
• 238000003776 cleavage reaction Methods 0.000 description 13
• 238000005859 coupling reaction Methods 0.000 description 13
• 229940078795 lactoferrin Drugs 0.000 description 13
• 230000007017 scission Effects 0.000 description 13
• 239000007787 solid Substances 0.000 description 13
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 230000008878 coupling Effects 0.000 description 12
• 238000010168 coupling process Methods 0.000 description 12
• 239000012634 fragment Substances 0.000 description 12
• 230000002949 hemolytic effect Effects 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
• 235000018102 proteins Nutrition 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• 238000010348 incorporation Methods 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• 210000004881 tumor cell Anatomy 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 108060003100 Magainin Proteins 0.000 description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
• 229940088710 antibiotic agent Drugs 0.000 description 9
• 230000003115 biocidal effect Effects 0.000 description 9
• 210000003743 erythrocyte Anatomy 0.000 description 9
• 235000020776 essential amino acid Nutrition 0.000 description 9
• 239000003797 essential amino acid Substances 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000012071 phase Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• 230000001988 toxicity Effects 0.000 description 9
• 231100000419 toxicity Toxicity 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 101000798100 Bos taurus Lactotransferrin Proteins 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 229940072440 bovine lactoferrin Drugs 0.000 description 8
• 210000000170 cell membrane Anatomy 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 238000011191 terminal modification Methods 0.000 description 8
• MGHMWKZOLAAOTD-DEOSSOPVSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(1h-indol-3-yl)propanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(=O)O)CC1=CNC2=CC=CC=C12 MGHMWKZOLAAOTD-DEOSSOPVSA-N 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• 239000004475 Arginine Substances 0.000 description 7
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 7
• 150000003862 amino acid derivatives Chemical class 0.000 description 7
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
• 229960003121 arginine Drugs 0.000 description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
• 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 7
• 230000003993 interaction Effects 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 238000012546 transfer Methods 0.000 description 7
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 230000002401 inhibitory effect Effects 0.000 description 6
• 238000011081 inoculation Methods 0.000 description 6
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 6
• 229960000310 isoleucine Drugs 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
• 229960005190 phenylalanine Drugs 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 125000003275 alpha amino acid group Chemical group 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 235000018417 cysteine Nutrition 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 230000006872 improvement Effects 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 125000005647 linker group Chemical group 0.000 description 5
• 230000002101 lytic effect Effects 0.000 description 5
• 108091005601 modified peptides Proteins 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• NTNKNFHIAFDCSJ-UHFFFAOYSA-N (2-nitrophenyl) thiohypochlorite Chemical compound [O-][N+](=O)C1=CC=CC=C1SCl NTNKNFHIAFDCSJ-UHFFFAOYSA-N 0.000 description 4
• 108700042778 Antimicrobial Peptides Proteins 0.000 description 4
• 102000044503 Antimicrobial Peptides Human genes 0.000 description 4
• 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 4
• 201000008808 Fibrosarcoma Diseases 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• 239000007821 HATU Substances 0.000 description 4
• 206010018910 Haemolysis Diseases 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
• 239000012980 RPMI-1640 medium Substances 0.000 description 4
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
• 125000000217 alkyl group Chemical group 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 201000011510 cancer Diseases 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 210000003527 eukaryotic cell Anatomy 0.000 description 4
• 230000008588 hemolysis Effects 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 150000002634 lipophilic molecules Chemical class 0.000 description 4
• 201000001441 melanoma Diseases 0.000 description 4
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 239000000816 peptidomimetic Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 230000002035 prolonged effect Effects 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 210000002966 serum Anatomy 0.000 description 4
• 241000894007 species Species 0.000 description 4
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
• 229960004441 tyrosine Drugs 0.000 description 4
• 239000004474 valine Substances 0.000 description 4
• 229960004295 valine Drugs 0.000 description 4
• GAUUPDQWKHTCAX-VIFPVBQESA-N (2s)-2-amino-3-(1-benzothiophen-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CSC2=C1 GAUUPDQWKHTCAX-VIFPVBQESA-N 0.000 description 3
• QTWZCODKTSUZJN-LJAQVGFWSA-N (2s)-5-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(O)=O)CCCN=C(N)NS(=O)(=O)C(C(C)=C1C)=C(C)C2=C1OC(C)(C)CC2 QTWZCODKTSUZJN-LJAQVGFWSA-N 0.000 description 3
• DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• GWKLNCUXOUHWLL-UHFFFAOYSA-N 2-(2-phenylethyl)guanidine Chemical compound NC(=N)NCCC1=CC=CC=C1 GWKLNCUXOUHWLL-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-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
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 230000021736 acetylation Effects 0.000 description 3
• 238000006640 acetylation reaction Methods 0.000 description 3
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 3
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 230000000975 bioactive effect Effects 0.000 description 3
• 239000006227 byproduct Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 150000007942 carboxylates Chemical class 0.000 description 3
• 239000006285 cell suspension Substances 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 239000006184 cosolvent Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 239000003599 detergent Substances 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 239000002158 endotoxin Substances 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 210000002950 fibroblast Anatomy 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 231100000053 low toxicity Toxicity 0.000 description 3
• 230000009401 metastasis Effects 0.000 description 3
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
• 235000013336 milk Nutrition 0.000 description 3
• 239000008267 milk Substances 0.000 description 3
• 210000004080 milk Anatomy 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
• 239000013642 negative control Substances 0.000 description 3
• FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 3
• 238000010647 peptide synthesis reaction Methods 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 210000001236 prokaryotic cell Anatomy 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 238000004626 scanning electron microscopy Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 150000003573 thiols Chemical class 0.000 description 3
• DTGKSKDOIYIVQL-QXFUBDJGSA-N (-)-borneol Chemical compound C1C[C@]2(C)[C@H](O)C[C@H]1C2(C)C DTGKSKDOIYIVQL-QXFUBDJGSA-N 0.000 description 2
• REPVLJRCJUVQFA-UYXSQOIJSA-N (1r,3r,4s,5s)-4,6,6-trimethylbicyclo[3.1.1]heptan-3-ol Chemical compound C1[C@@]2([H])[C@H](C)[C@H](O)C[C@]1([H])C2(C)C REPVLJRCJUVQFA-UYXSQOIJSA-N 0.000 description 2
• MDFWXZBEVCOVIO-WEDXCCLWSA-N (1r,3s,4r)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-amine Chemical compound C1C[C@@]2(C)[C@@H](N)C[C@]1([H])C2(C)C MDFWXZBEVCOVIO-WEDXCCLWSA-N 0.000 description 2
• LKRSUSMQXGCKKX-QHCPKHFHSA-N (2S)-2-amino-2,3-ditert-butyl-3-(1H-indol-3-yl)-4,4-dimethylpentanoic acid Chemical compound C(C)(C)(C)C([C@](N)(C(=O)O)C(C)(C)C)(C1=CNC2=CC=CC=C12)C(C)(C)C LKRSUSMQXGCKKX-QHCPKHFHSA-N 0.000 description 2
• JTTHKOPSMAVJFE-SECBINFHSA-N (2r)-2-azaniumyl-4-phenylbutanoate Chemical compound [O-]C(=O)[C@H]([NH3+])CCC1=CC=CC=C1 JTTHKOPSMAVJFE-SECBINFHSA-N 0.000 description 2
• NJVBZNOXROKNRD-HNNXBMFYSA-N (2s)-2-[(2,6-dichlorophenyl)methylamino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NCC=1C(=CC=CC=1Cl)Cl)C1=CC=C(O)C=C1 NJVBZNOXROKNRD-HNNXBMFYSA-N 0.000 description 2
• ADJZXDVMJPTFKT-JTQLQIEISA-N (2s)-2-azaniumyl-4-(1h-indol-3-yl)butanoate Chemical compound C1=CC=C2C(CC[C@H](N)C(O)=O)=CNC2=C1 ADJZXDVMJPTFKT-JTQLQIEISA-N 0.000 description 2
• WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 2
• MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• IAQHPZFALQQESM-UHFFFAOYSA-N 1-pentylbicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(CCCCC)CC2 IAQHPZFALQQESM-UHFFFAOYSA-N 0.000 description 2
• KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical compound C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 description 2
• OGRAOKJKVGDSFR-UHFFFAOYSA-N 2,3,5-trimethylphenol Chemical compound CC1=CC(C)=C(C)C(O)=C1 OGRAOKJKVGDSFR-UHFFFAOYSA-N 0.000 description 2
• FRAKHUZTNLUGPB-UHFFFAOYSA-N 3,3,5-trimethyl-7-azabicyclo[3.2.1]octane Chemical compound C1C2NCC1(C)CC(C)(C)C2 FRAKHUZTNLUGPB-UHFFFAOYSA-N 0.000 description 2
• ZAQXSMCYFQJRCQ-UHFFFAOYSA-N 3-(1-adamantyl)-2-azaniumylpropanoate Chemical compound C1C(C2)CC3CC2CC1(CC(N)C(O)=O)C3 ZAQXSMCYFQJRCQ-UHFFFAOYSA-N 0.000 description 2
• RXUUYFUQAGICCD-UHFFFAOYSA-N 3-noradamantanecarboxylic acid Chemical compound C1C(C2)C3(C(=O)O)CC2CC1C3 RXUUYFUQAGICCD-UHFFFAOYSA-N 0.000 description 2
• IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• RVOKNSFEAOYULQ-UHFFFAOYSA-N 8-Mercapto-p-menthan-3-one Chemical compound CC1CCC(C(C)(C)S)C(=O)C1 RVOKNSFEAOYULQ-UHFFFAOYSA-N 0.000 description 2
• COQRKPRIDRDOOG-UHFFFAOYSA-N 9-ethylbicyclo[3.3.1]nonan-9-ol Chemical compound C1CCC2CCCC1C2(O)CC COQRKPRIDRDOOG-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 108010050820 Antimicrobial Cationic Peptides Proteins 0.000 description 2
• 102000014133 Antimicrobial Cationic Peptides Human genes 0.000 description 2
• 206010003445 Ascites Diseases 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
• 108010023063 Bacto-peptone Proteins 0.000 description 2
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 108050004290 Cecropin Proteins 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• 102000005593 Endopeptidases Human genes 0.000 description 2
• 108010059378 Endopeptidases Proteins 0.000 description 2
• 241000192125 Firmicutes 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
• 102000001554 Hemoglobins Human genes 0.000 description 2
• 108010054147 Hemoglobins Proteins 0.000 description 2
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
• 101000798114 Homo sapiens Lactotransferrin Proteins 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 101800004761 Magainin-2 Proteins 0.000 description 2
• RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• NFVNYBJCJGKVQK-ZDUSSCGKSA-N N-[(Tert-butoxy)carbonyl]-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CNC2=C1 NFVNYBJCJGKVQK-ZDUSSCGKSA-N 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 229960000583 acetic acid Drugs 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 230000004721 adaptive immunity Effects 0.000 description 2
• 238000012867 alanine scanning Methods 0.000 description 2
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
• 125000006242 amine protecting group Chemical group 0.000 description 2
• 230000003698 anagen phase Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 235000009582 asparagine Nutrition 0.000 description 2
• 229960001230 asparagine Drugs 0.000 description 2
• 239000012911 assay medium Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 230000003385 bacteriostatic effect Effects 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000007385 chemical modification Methods 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000010586 diagram Methods 0.000 description 2
• OXBMFCGRQJNAOY-UHFFFAOYSA-N dimethyl cubane-1,4-dicarboxylate Chemical compound C12C3C4(C(=O)OC)C1C1C4C3C12C(=O)OC OXBMFCGRQJNAOY-UHFFFAOYSA-N 0.000 description 2
• 239000012153 distilled water Substances 0.000 description 2
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
• 229940066758 endopeptidases Drugs 0.000 description 2
• 230000007515 enzymatic degradation Effects 0.000 description 2
• KQGQONPKSKUHHT-AWEZNQCLSA-N ethyl (2s)-2-acetamido-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@@H](C(=O)OCC)NC(C)=O)=CNC2=C1 KQGQONPKSKUHHT-AWEZNQCLSA-N 0.000 description 2
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
• 239000000834 fixative Substances 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 238000005534 hematocrit Methods 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 102000050459 human LTF Human genes 0.000 description 2
• SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• YFMJTLUPSMCTOQ-UHFFFAOYSA-N isoquinoline-5-sulfonic acid Chemical compound N1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 YFMJTLUPSMCTOQ-UHFFFAOYSA-N 0.000 description 2
• 230000002147 killing effect Effects 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 229920006008 lipopolysaccharide Polymers 0.000 description 2
• AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
• 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 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 2
• 229960003085 meticillin Drugs 0.000 description 2
• 239000007922 nasal spray Substances 0.000 description 2
• 235000016709 nutrition Nutrition 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 239000004417 polycarbonate Substances 0.000 description 2
• 229920000515 polycarbonate Polymers 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000003910 polypeptide antibiotic agent Substances 0.000 description 2
• 229920005990 polystyrene resin Polymers 0.000 description 2
• 238000012987 post-synthetic modification Methods 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000007086 side reaction Methods 0.000 description 2
• 239000007790 solid phase Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000002700 tablet coating Substances 0.000 description 2
• 238000009492 tablet coating Methods 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 229960002898 threonine Drugs 0.000 description 2
• 231100000048 toxicity data Toxicity 0.000 description 2
• 238000005809 transesterification reaction Methods 0.000 description 2
• 238000004627 transmission electron microscopy Methods 0.000 description 2
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 230000007306 turnover Effects 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 2
• DOUJYVMLNKRFHE-IBGZPJMESA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)COC(C)(C)C)OC1=C(F)C(F)=C(F)C(F)=C1F DOUJYVMLNKRFHE-IBGZPJMESA-N 0.000 description 1
• TZEGAVSWQUEHAQ-QHCPKHFHSA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(C)C)OC1=C(F)C(F)=C(F)C(F)=C1F TZEGAVSWQUEHAQ-QHCPKHFHSA-N 0.000 description 1
• WKHPSOMXNCTXPK-QFIPXVFZSA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-phenylpropanoate Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1OC(=O)[C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CC1=CC=CC=C1 WKHPSOMXNCTXPK-QFIPXVFZSA-N 0.000 description 1
• NTQJCLLWLHKJLU-IBGZPJMESA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-methylpentanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CC(C)C)OC1=C(F)C(F)=C(F)C(F)=C1F NTQJCLLWLHKJLU-IBGZPJMESA-N 0.000 description 1
• OKDPSRDTLNXPFQ-SFHVURJKSA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-methylsulfanylbutanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CCSC)OC1=C(F)C(F)=C(F)C(F)=C1F OKDPSRDTLNXPFQ-SFHVURJKSA-N 0.000 description 1
• CJXZXBGKOSXBFR-NSHDSACASA-N (2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C)OC1=C(F)C(F)=C(F)C(F)=C1F CJXZXBGKOSXBFR-NSHDSACASA-N 0.000 description 1
• FYZSBHSHLNJGPS-RZFZLAGVSA-N (2,3,4,5,6-pentafluorophenyl) (2s,3s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylpentanoate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)[C@@H](C)CC)OC1=C(F)C(F)=C(F)C(F)=C1F FYZSBHSHLNJGPS-RZFZLAGVSA-N 0.000 description 1
• WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• IEWNVASEEYFBFI-INIZCTEOSA-N (2S)-2-amino-3-[1-(4-methylphenyl)sulfonylindol-3-yl]propanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=CC=C2C(C[C@H](N)C(O)=O)=C1 IEWNVASEEYFBFI-INIZCTEOSA-N 0.000 description 1
• IYKLZBIWFXPUCS-SECBINFHSA-N (2r)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-SECBINFHSA-N 0.000 description 1
• GUDHMDVRURNAHL-SNVBAGLBSA-N (2r)-2-amino-2-(2,3-dihydro-1h-inden-2-yl)acetic acid Chemical compound C1=CC=C2CC([C@@H](N)C(O)=O)CC2=C1 GUDHMDVRURNAHL-SNVBAGLBSA-N 0.000 description 1
• PECGVEGMRUZOML-CQSZACIVSA-N (2r)-2-amino-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C([C@@H](N)C(O)=O)C1=CC=CC=C1 PECGVEGMRUZOML-CQSZACIVSA-N 0.000 description 1
• GAUUPDQWKHTCAX-SECBINFHSA-N (2r)-2-amino-3-(1-benzothiophen-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CSC2=C1 GAUUPDQWKHTCAX-SECBINFHSA-N 0.000 description 1
• TVIDEEHSOPHZBR-CQSZACIVSA-N (2r)-2-azaniumyl-3-(4-benzoylphenyl)propanoate Chemical compound C1=CC(C[C@@H](N)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 TVIDEEHSOPHZBR-CQSZACIVSA-N 0.000 description 1
• JCZLABDVDPYLRZ-CQSZACIVSA-N (2r)-2-azaniumyl-3-(4-phenylphenyl)propanoate Chemical compound C1=CC(C[C@@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 JCZLABDVDPYLRZ-CQSZACIVSA-N 0.000 description 1
• OFYAYGJCPXRNBL-GFCCVEGCSA-N (2r)-2-azaniumyl-3-naphthalen-1-ylpropanoate Chemical compound C1=CC=C2C(C[C@@H]([NH3+])C([O-])=O)=CC=CC2=C1 OFYAYGJCPXRNBL-GFCCVEGCSA-N 0.000 description 1
• TZVGIHUGMJIKMD-ZDUSSCGKSA-N (2s)-2-acetamido-4-(1h-indol-3-yl)butanoic acid Chemical compound C1=CC=C2C(CC[C@H](NC(=O)C)C(O)=O)=CNC2=C1 TZVGIHUGMJIKMD-ZDUSSCGKSA-N 0.000 description 1
• WXYGVKADAIJGHB-ZDUSSCGKSA-N (2s)-3-(1h-indol-2-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC=C2NC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC2=C1 WXYGVKADAIJGHB-ZDUSSCGKSA-N 0.000 description 1
• DODHIGHXRDNRPP-SFHVURJKSA-N (2s)-3-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OCC1=C(Cl)C=CC=C1Cl DODHIGHXRDNRPP-SFHVURJKSA-N 0.000 description 1
• DVBUCBXGDWWXNY-SFHVURJKSA-N (2s)-5-(diaminomethylideneamino)-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C3=CC=CC=C3C2=C1 DVBUCBXGDWWXNY-SFHVURJKSA-N 0.000 description 1
• BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
• REUAXQZIRFXQML-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1CC2C(N)CN1CC2 REUAXQZIRFXQML-UHFFFAOYSA-N 0.000 description 1
• RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
• XFZYPCNLVHSQTG-UHFFFAOYSA-N 2,2,5,7,8-pentamethyl-3,4-dihydrochromene Chemical compound C1CC(C)(C)OC2=C(C)C(C)=CC(C)=C21 XFZYPCNLVHSQTG-UHFFFAOYSA-N 0.000 description 1
• UXUOVYKDMGFUDU-UHFFFAOYSA-N 2,2,5,7,8-pentamethyl-3,4-dihydrochromene-6-sulfonyl chloride Chemical compound C1CC(C)(C)OC2=C1C(C)=C(S(Cl)(=O)=O)C(C)=C2C UXUOVYKDMGFUDU-UHFFFAOYSA-N 0.000 description 1
• QTNLSYMRKYVTHJ-UHFFFAOYSA-N 2-(3-bicyclo[2.2.1]hept-2-enyl)acetic acid Chemical compound C1CC2C(CC(=O)O)=CC1C2 QTNLSYMRKYVTHJ-UHFFFAOYSA-N 0.000 description 1
• VUCNQOPCYRJCGQ-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenoxy]acetic acid Chemical compound OCC1=CC=C(OCC(O)=O)C=C1 VUCNQOPCYRJCGQ-UHFFFAOYSA-N 0.000 description 1
• SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical class [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
• QQOMQLYQAXGHSU-UHFFFAOYSA-N 236TMPh Natural products CC1=CC=C(C)C(O)=C1C QQOMQLYQAXGHSU-UHFFFAOYSA-N 0.000 description 1
• JPZXHKDZASGCLU-GFCCVEGCSA-N 3-(2-Naphthyl)-D-Alanine Chemical compound C1=CC=CC2=CC(C[C@@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-GFCCVEGCSA-N 0.000 description 1
• BTXXTMOWISPQSJ-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-one Chemical compound CC(=O)CC(F)(F)F BTXXTMOWISPQSJ-UHFFFAOYSA-N 0.000 description 1
• JFNIDIDTWDBBFR-UHFFFAOYSA-N 4-(2-phenylethylsulfanyl)phenol Chemical class C1=CC(O)=CC=C1SCCC1=CC=CC=C1 JFNIDIDTWDBBFR-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• AIDYQYOPUBOMTR-FQEVSTJZSA-N 5-o-tert-butyl 1-o-(2,3,4,5,6-pentafluorophenyl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanedioate Chemical compound O=C([C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CCC(=O)OC(C)(C)C)OC1=C(F)C(F)=C(F)C(F)=C1F AIDYQYOPUBOMTR-FQEVSTJZSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• OUGMRQJTULXVDC-UHFFFAOYSA-N 9h-fluoren-9-amine Chemical compound C1=CC=C2C(N)C3=CC=CC=C3C2=C1 OUGMRQJTULXVDC-UHFFFAOYSA-N 0.000 description 1
• BQACOLQNOUYJCE-FYZZASKESA-N Abietic acid Natural products CC(C)C1=CC2=CC[C@]3(C)[C@](C)(CCC[C@@]3(C)C(=O)O)[C@H]2CC1 BQACOLQNOUYJCE-FYZZASKESA-N 0.000 description 1
• RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 229920003319 Araldite® Polymers 0.000 description 1
• 108010077805 Bacterial Proteins Proteins 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
• 241001529572 Chaceon affinis Species 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 108010002069 Defensins Proteins 0.000 description 1
• 102000000541 Defensins Human genes 0.000 description 1
• 101710088194 Dehydrogenase Proteins 0.000 description 1
• 108020005199 Dehydrogenases Proteins 0.000 description 1
• 206010056340 Diabetic ulcer Diseases 0.000 description 1
• YCAGGFXSFQFVQL-UHFFFAOYSA-N Endothion Chemical compound COC1=COC(CSP(=O)(OC)OC)=CC1=O YCAGGFXSFQFVQL-UHFFFAOYSA-N 0.000 description 1
• 241000588697 Enterobacter cloacae Species 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 102000018389 Exopeptidases Human genes 0.000 description 1
• 108010091443 Exopeptidases Proteins 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000941289 Homo sapiens Hepatic triacylglycerol lipase Proteins 0.000 description 1
• 101001047912 Homo sapiens Hydroxymethylglutaryl-CoA lyase, mitochondrial Proteins 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 108091006975 Iron transporters Proteins 0.000 description 1
• 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
• 150000008575 L-amino acids Chemical class 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 description 1
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
• 239000000232 Lipid Bilayer Substances 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 108010036176 Melitten Proteins 0.000 description 1
• 206010028470 Mycoplasma infections Diseases 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• DZTHIGRZJZPRDV-LBPRGKRZSA-N N-acetyl-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-LBPRGKRZSA-N 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• 101800004819 PGLa Proteins 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
• 102000057297 Pepsin A Human genes 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 206010041925 Staphylococcal infections Diseases 0.000 description 1
• 241000191967 Staphylococcus aureus Species 0.000 description 1
• 241000191963 Staphylococcus epidermidis Species 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
• OHGNSVACHBZKSS-KWQFWETISA-N Trp-Ala Chemical class C1=CC=C2C(C[C@H]([NH3+])C(=O)N[C@@H](C)C([O-])=O)=CNC2=C1 OHGNSVACHBZKSS-KWQFWETISA-N 0.000 description 1
• COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 241000269370 Xenopus <genus> Species 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 230000000397 acetylating effect Effects 0.000 description 1
• 238000010306 acid treatment Methods 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001412 amines Chemical group 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000000613 asparagine group Chemical class N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
• 239000003659 bee venom Substances 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 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
• 239000011230 binding agent Substances 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 230000003592 biomimetic effect Effects 0.000 description 1
• JCZLABDVDPYLRZ-AWEZNQCLSA-N biphenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 JCZLABDVDPYLRZ-AWEZNQCLSA-N 0.000 description 1
• HOQPTLCRWVZIQZ-UHFFFAOYSA-H bis[[2-(5-hydroxy-4,7-dioxo-1,3,2$l^{2}-dioxaplumbepan-5-yl)acetyl]oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HOQPTLCRWVZIQZ-UHFFFAOYSA-H 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000005587 carbonate group Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 229940096529 carboxypolymethylene Drugs 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 238000002983 circular dichroism Methods 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000005056 compaction Methods 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 229910000365 copper sulfate Inorganic materials 0.000 description 1
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 230000001461 cytolytic effect Effects 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 239000002254 cytotoxic agent Substances 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 238000010908 decantation Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 230000006334 disulfide bridging Effects 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 238000001493 electron microscopy Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000006862 enzymatic digestion Effects 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 244000144992 flock Species 0.000 description 1
• IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000012239 gene modification Methods 0.000 description 1
• 230000005017 genetic modification Effects 0.000 description 1
• 235000013617 genetically modified food Nutrition 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 235000014304 histidine Nutrition 0.000 description 1
• 230000009215 host defense mechanism Effects 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000006054 immunological memory Effects 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 150000002475 indoles Chemical class 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 239000002054 inoculum Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
• MDFWXZBEVCOVIO-UHFFFAOYSA-N isobornylamine Natural products C1CC2(C)C(N)CC1C2(C)C MDFWXZBEVCOVIO-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 229940124280 l-arginine Drugs 0.000 description 1
• 229950008325 levothyroxine Drugs 0.000 description 1
• SBXXSUDPJJJJLC-YDALLXLXSA-M liothyronine sodium Chemical compound [Na+].IC1=CC(C[C@H](N)C([O-])=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 SBXXSUDPJJJJLC-YDALLXLXSA-M 0.000 description 1
• 125000003473 lipid group Chemical group 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 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 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
• 239000000693 micelle Substances 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 231100000065 noncytotoxic Toxicity 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• TVIDEEHSOPHZBR-AWEZNQCLSA-N para-(benzoyl)-phenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 TVIDEEHSOPHZBR-AWEZNQCLSA-N 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 125000005541 phosphonamide group Chemical group 0.000 description 1
• 125000004437 phosphorous atom Chemical group 0.000 description 1
• 150000003017 phosphorus Chemical class 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920002689 polyvinyl acetate Polymers 0.000 description 1
• 239000011118 polyvinyl acetate Substances 0.000 description 1
• 229940075065 polyvinyl acetate Drugs 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 244000062645 predators Species 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 125000001749 primary amide group Chemical group 0.000 description 1
• 150000003140 primary amides Chemical class 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 229930195734 saturated hydrocarbon Chemical group 0.000 description 1
• 125000003156 secondary amide group Chemical group 0.000 description 1
• 150000003334 secondary amides Chemical class 0.000 description 1
• 208000011581 secondary neoplasm Diseases 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• JMHCCAYJTTWMCX-QWPJCUCISA-M sodium;(2s)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoate;pentahydrate Chemical compound O.O.O.O.O.[Na+].IC1=CC(C[C@H](N)C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 JMHCCAYJTTWMCX-QWPJCUCISA-M 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000011885 synergistic combination Substances 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 238000012956 testing procedure Methods 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010215 titanium dioxide Nutrition 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000006257 total synthesis reaction Methods 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 229930195735 unsaturated hydrocarbon Chemical group 0.000 description 1
• 229940096998 ursolic acid Drugs 0.000 description 1
• PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• GUDHMDVRURNAHL-JTQLQIEISA-N α-amino-2-indanacetic acid Chemical compound C1=CC=C2CC([C@H](N)C(O)=O)CC2=C1 GUDHMDVRURNAHL-JTQLQIEISA-N 0.000 description 1