ghk-cu cosmetic powder Copper Peptide for Sale 2g GHK Copper Peptide Cosmetic

Arvaniti, M

Directions for Use: Administration: ZENCOBAL 1500 I.V

Researchers utilise this peptide to explore mechanisms of fat oxidation, lipid storage regulation, and metabolic efficiency in controlled experimental models

Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) Filing date Publication date Application filed by Hangzhou Sinopep Aosainuo Pharmaceutical Technology Development Co ltd filed Critical Hangzhou Sinopep Aosainuo Pharmaceutical Technology Development Co ltd Priority to CN202111615700.8A priority Critical patent/CN114249808B/en Publication of CN114249808A publication Critical patent/CN114249808A/en Application granted granted Critical Publication of CN114249808B publication Critical patent/CN114249808B/en Active legal-status Critical Current Anticipated expiration legal-status Critical Links Espacenet Global Dossier Discuss 108700007784 cagrilintide Proteins 0.000 title claims abstract description 63 229940062978 cagrilintide Drugs 0.000 title claims abstract description 56 238000001308 synthesis method Methods 0.000 title description 11 238000007363 ring formation reaction Methods 0.000 claims abstract description 33 150000001413 amino acids Chemical class 0.000 claims abstract description 24 108010016626 Dipeptides Proteins 0.000 claims abstract description 23 238000006243 chemical reaction Methods 0.000 claims abstract description 15 238000000034 method Methods 0.000 claims abstract description 15 230000002194 synthesizing effect Effects 0.000 claims abstract description 12 238000005859 coupling reaction Methods 0.000 claims abstract description 11 ZPGDWQNBZYOZTI-SFHVURJKSA-N (2s)-1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-SFHVURJKSA-N 0.000 claims description 47 108090000765 processed proteins & peptides Proteins 0.000 claims description 40 239000003153 chemical reaction reagent Substances 0.000 claims description 39 239000000243 solution Substances 0.000 claims description 31 YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 28 229920005989 resin Polymers 0.000 claims description 24 239000011347 resin Substances 0.000 claims description 24 CBPJQFCAFFNICX-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-methylpentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC(C)C)C(O)=O)C3=CC=CC=C3C2=C1 CBPJQFCAFFNICX-IBGZPJMESA-N 0.000 claims description 18 KJYAFJQCGPUXJY-UMSFTDKQSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-oxo-4-(tritylamino)butanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(=O)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 KJYAFJQCGPUXJY-UMSFTDKQSA-N 0.000 claims description 17 XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17 LZOLWEQBVPVDPR-VLIAUNLRSA-N (2s,3r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]butanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@H](OC(C)(C)C)C)C(O)=O)C3=CC=CC=C3C2=C1 LZOLWEQBVPVDPR-VLIAUNLRSA-N 0.000 claims description 16 RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16 NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14 SJVFAHZPLIXNDH-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C1=CC=CC=C1 SJVFAHZPLIXNDH-QFIPXVFZSA-N 0.000 claims description 13 238000005406 washing Methods 0.000 claims description 13 239000002904 solvent Substances 0.000 claims description 12 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 11 238000001514 detection method Methods 0.000 claims description 11 238000001035 drying Methods 0.000 claims description 11 KLBPUVPNPAJWHZ-UMSFTDKQSA-N (2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 KLBPUVPNPAJWHZ-UMSFTDKQSA-N 0.000 claims description 10 NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 claims description 10 LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10 NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 10 239000000203 mixture Substances 0.000 claims description 10 239000000047 product Substances 0.000 claims description 10 239000008213 purified water Substances 0.000 claims description 10 238000005336 cracking Methods 0.000 claims description 9 QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 claims description 7 HNICLNKVURBTKV-NDEPHWFRSA-N (2s)-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-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)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C HNICLNKVURBTKV-NDEPHWFRSA-N 0.000 claims description 7 238000001914 filtration Methods 0.000 claims description 7 238000001556 precipitation Methods 0.000 claims description 7 238000010168 coupling process Methods 0.000 claims description 6 239000012043 crude product Substances 0.000 claims description 6 238000010511 deprotection reaction Methods 0.000 claims description 6 239000007790 solid phase Substances 0.000 claims description 6 238000005303 weighing Methods 0.000 claims description 6 XXMYDXUIZKNHDT-QNGWXLTQSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(1-tritylimidazol-4-yl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXMYDXUIZKNHDT-QNGWXLTQSA-N 0.000 claims description 5 REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 claims description 5 JZTKZVJMSCONAK-INIZCTEOSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-hydroxypropanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CO)C(O)=O)C3=CC=CC=C3C2=C1 JZTKZVJMSCONAK-INIZCTEOSA-N 0.000 claims description 5 UGNIYGNGCNXHTR-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-SFHVURJKSA-N 0.000 claims description 5 OTKXCALUHMPIGM-FQEVSTJZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 OTKXCALUHMPIGM-FQEVSTJZSA-N 0.000 claims description 5 WDGICUODAOGOMO-DHUJRADRSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-oxo-5-(tritylamino)pentanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CC(=O)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WDGICUODAOGOMO-DHUJRADRSA-N 0.000 claims description 5 UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 claims description 5 QXVFEIPAZSXRGM-DJJJIMSYSA-N (2s,3s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylpentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@@H](C)CC)C(O)=O)C3=CC=CC=C3C2=C1 QXVFEIPAZSXRGM-DJJJIMSYSA-N 0.000 claims description 5 GOPWHXPXSPIIQZ-FQEVSTJZSA-N (4s)-4-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(O)=O)C(=O)OC(C)(C)C)C3=CC=CC=C3C2=C1 GOPWHXPXSPIIQZ-FQEVSTJZSA-N 0.000 claims description 5 ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5 -1 Fmoc-Ser (Pro-Pro-OH Chemical compound 0.000 claims description 5 230000008878 coupling Effects 0.000 claims description 5 229910052740 iodine Inorganic materials 0.000 claims description 5 239000011630 iodine Substances 0.000 claims description 5 PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims description 4 239000011259 mixed solution Substances 0.000 claims description 4 238000005086 pumping Methods 0.000 claims description 4 238000006467 substitution reaction Methods 0.000 claims description 4 229920003180 amino resin Polymers 0.000 claims description 3 238000003776 cleavage reaction Methods 0.000 claims description 3 230000007017 scission Effects 0.000 claims description 3 ZPGDWQNBZYOZTI-UHFFFAOYSA-N 1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-UHFFFAOYSA-N 0.000 claims description 2 XXSCONYSQQLHTH-UHFFFAOYSA-N 9h-fluoren-9-ylmethanol Chemical compound C1=CC=C2C(CO)C3=CC=CC=C3C2=C1 XXSCONYSQQLHTH-UHFFFAOYSA-N 0.000 claims description 2 230000003213 activating effect Effects 0.000 claims description 2 238000005374 membrane filtration Methods 0.000 claims description 2 230000001376 precipitating effect Effects 0.000 claims description 2 230000008961 swelling Effects 0.000 claims description 2 238000010189 synthetic method Methods 0.000 claims description 2 238000001471 micro-filtration Methods 0.000 claims 1 125000003275 alpha amino acid group Chemical group 0.000 abstract description 5 WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27 OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9 MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 9 238000002360 preparation method Methods 0.000 description 9 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 7 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 7 239000007864 aqueous solution Substances 0.000 description 6 230000000052 comparative effect Effects 0.000 description 5 CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 4 239000012071 phase Substances 0.000 description 4 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 3 239000002253 acid Substances 0.000 description 3 230000004913 activation Effects 0.000 description 3 238000004458 analytical method Methods 0.000 description 3 238000004090 dissolution Methods 0.000 description 3 238000011031 large-scale manufacturing process Methods 0.000 description 3 239000012528 membrane Substances 0.000 description 3 229920001184 polypeptide Polymers 0.000 description 3 239000000843 powder Substances 0.000 description 3 239000002244 precipitate Substances 0.000 description 3 102000004196 processed proteins & peptides Human genes 0.000 description 3 238000000746 purification Methods 0.000 description 3 238000001291 vacuum drying Methods 0.000 description 3 102000009027 Albumins Human genes 0.000 description 2 108010088751 Albumins Proteins 0.000 description 2 208000008589 Obesity Diseases 0.000 description 2 GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2 239000012351 deprotecting agent Substances 0.000 description 2 NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2 235000020824 obesity Nutrition 0.000 description 2 230000003285 pharmacodynamic effect Effects 0.000 description 2 108010029667 pramlintide Proteins 0.000 description 2 229960003611 pramlintide Drugs 0.000 description 2 NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 2 230000002195 synergetic effect Effects 0.000 description 2 OYULCCKKLJPNPU-DIFFPNOSSA-N (2s,3r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-hydroxybutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@H](O)C)C(O)=O)C3=CC=CC=C3C2=C1 OYULCCKKLJPNPU-DIFFPNOSSA-N 0.000 description 1 208000024172 Cardiovascular disease Diseases 0.000 description 1 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1 102400000321 Glucagon Human genes 0.000 description 1 108060003199 Glucagon Proteins 0.000 description 1 DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1 WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1 102000004877 Insulin Human genes 0.000 description 1 108090001061 Insulin Proteins 0.000 description 1 208000001145 Metabolic Syndrome Diseases 0.000 description 1 102100040918 Pro-glucagon Human genes 0.000 description 1 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1 230000033228 biological regulation Effects 0.000 description 1 230000015572 biosynthetic process Effects 0.000 description 1 238000004364 calculation method Methods 0.000 description 1 235000019577 caloric intake Nutrition 0.000 description 1 230000007547 defect Effects 0.000 description 1 206010012601 diabetes mellitus Diseases 0.000 description 1 229940079593 drug Drugs 0.000 description 1 239000003814 drug Substances 0.000 description 1 239000012634 fragment Substances 0.000 description 1 230000030136 gastric emptying Effects 0.000 description 1 MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1 229960004666 glucagon Drugs 0.000 description 1 239000008103 glucose Substances 0.000 description 1 229940088597 hormone Drugs 0.000 description 1 239000005556 hormone Substances 0.000 description 1 235000003642 hunger Nutrition 0.000 description 1 229940125396 insulin Drugs 0.000 description 1 239000012982 microporous membrane Substances 0.000 description 1 230000000291 postprandial effect Effects 0.000 description 1 230000036186 satiety Effects 0.000 description 1 235000019627 satiety Nutrition 0.000 description 1 230000019491 signal transduction Effects 0.000 description 1 238000003786 synthesis reaction Methods 0.000 description 1 Images Classifications CCHEMISTRY

Different expression of occludin and ZO-1 in primary and metastatic liver tumors