CN108948109B - 雷酚内酯苷类化合物及其应用 - Google Patents
雷酚内酯苷类化合物及其应用 Download PDFInfo
- Publication number
- CN108948109B CN108948109B CN201810526970.3A CN201810526970A CN108948109B CN 108948109 B CN108948109 B CN 108948109B CN 201810526970 A CN201810526970 A CN 201810526970A CN 108948109 B CN108948109 B CN 108948109B
- Authority
- CN
- China
- Prior art keywords
- triptophenolide
- glycoside
- leu
- ser
- val
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- -1 glycoside compound Chemical class 0.000 title claims abstract description 37
- 229930182470 glycoside Natural products 0.000 title claims abstract description 36
- VIYFRTDWJXBEDM-UHFFFAOYSA-N Triptophenolide Natural products CC(C)c1ccc2c(CCC3C4=COC(=O)C4=CCC23C)c1O VIYFRTDWJXBEDM-UHFFFAOYSA-N 0.000 claims abstract description 41
- 108700023372 Glycosyltransferases Proteins 0.000 claims abstract description 17
- 102000051366 Glycosyltransferases Human genes 0.000 claims abstract description 15
- 238000006911 enzymatic reaction Methods 0.000 claims abstract description 5
- 150000002338 glycosides Chemical class 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 15
- YKUJZZHGTWVWHA-UHFFFAOYSA-N triptolide Natural products COC12CC3OC3(C(C)C)C(O)C14OC4CC5C6=C(CCC25C)C(=O)OC6 YKUJZZHGTWVWHA-UHFFFAOYSA-N 0.000 claims description 12
- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical compound O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](O)[C@]21[C@H]3O1 DFBIRQPKNDILPW-CIVMWXNOSA-N 0.000 claims description 7
- 239000000348 glycosyl donor Substances 0.000 claims description 6
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 claims description 3
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical group O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 claims description 3
- 238000012546 transfer Methods 0.000 claims description 3
- HDYANYHVCAPMJV-UHFFFAOYSA-N Uridine diphospho-D-glucuronic acid Natural products O1C(N2C(NC(=O)C=C2)=O)C(O)C(O)C1COP(O)(=O)OP(O)(=O)OC1OC(C(O)=O)C(O)C(O)C1O HDYANYHVCAPMJV-UHFFFAOYSA-N 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- HDYANYHVCAPMJV-USQUEEHTSA-N udp-glucuronic acid Chemical compound O([P@](O)(=O)O[P@](O)(=O)OC[C@H]1[C@@H]([C@H]([C@@H](O1)N1C(NC(=O)C=C1)=O)O)O)[C@H]1O[C@@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HDYANYHVCAPMJV-USQUEEHTSA-N 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 21
- 241000830536 Tripterygium wilfordii Species 0.000 description 19
- 235000015398 thunder god vine Nutrition 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- KPXIBWGPZSPABK-FXAWDEMLSA-N (3bR,9bS)-6-hydroxy-9b-methyl-7-propan-2-yl-3,3b,4,5,10,11-hexahydronaphtho[2,1-e]isobenzofuran-1-one Chemical compound C1C[C@]2(C)C3=CC=C(C(C)C)C(O)=C3CC[C@H]2C2=C1C(=O)OC2 KPXIBWGPZSPABK-FXAWDEMLSA-N 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000545405 Tripterygium Species 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000001976 enzyme digestion Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 229940124622 immune-modulator drug Drugs 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000208365 Celastraceae Species 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- ZFADFBPRMSBPOT-KKUMJFAQSA-N Gln-Arg-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O ZFADFBPRMSBPOT-KKUMJFAQSA-N 0.000 description 2
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BKIOKSLLAAZYTC-KKHAAJSZSA-N Thr-Val-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O BKIOKSLLAAZYTC-KKHAAJSZSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 238000000246 agarose gel electrophoresis Methods 0.000 description 2
- 108010013835 arginine glutamate Proteins 0.000 description 2
- 108010077245 asparaginyl-proline Proteins 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000005100 correlation spectroscopy Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000003929 heteronuclear multiple quantum coherence Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 2
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 108010051242 phenylalanylserine Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 108010048818 seryl-histidine Proteins 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
- 230000009466 transformation Effects 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- ZDYNWWQXFRUOEO-XDTLVQLUSA-N Ala-Gln-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDYNWWQXFRUOEO-XDTLVQLUSA-N 0.000 description 1
- BGNLUHXLSAQYRQ-FXQIFTODSA-N Ala-Glu-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BGNLUHXLSAQYRQ-FXQIFTODSA-N 0.000 description 1
- GSHKMNKPMLXSQW-KBIXCLLPSA-N Ala-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C)N GSHKMNKPMLXSQW-KBIXCLLPSA-N 0.000 description 1
- LBYMZCVBOKYZNS-CIUDSAMLSA-N Ala-Leu-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O LBYMZCVBOKYZNS-CIUDSAMLSA-N 0.000 description 1
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 1
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 1
- SYIFFFHSXBNPMC-UWJYBYFXSA-N Ala-Ser-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N SYIFFFHSXBNPMC-UWJYBYFXSA-N 0.000 description 1
- LSMDIAAALJJLRO-XQXXSGGOSA-N Ala-Thr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O LSMDIAAALJJLRO-XQXXSGGOSA-N 0.000 description 1
- XCIGOVDXZULBBV-DCAQKATOSA-N Ala-Val-Lys Chemical compound CC(C)[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](CCCCN)C(O)=O XCIGOVDXZULBBV-DCAQKATOSA-N 0.000 description 1
- 229940123407 Androgen receptor antagonist Drugs 0.000 description 1
- JCAISGGAOQXEHJ-ZPFDUUQYSA-N Arg-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N JCAISGGAOQXEHJ-ZPFDUUQYSA-N 0.000 description 1
- GOWZVQXTHUCNSQ-NHCYSSNCSA-N Arg-Glu-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O GOWZVQXTHUCNSQ-NHCYSSNCSA-N 0.000 description 1
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 1
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 1
- ISVACHFCVRKIDG-SRVKXCTJSA-N Arg-Val-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O ISVACHFCVRKIDG-SRVKXCTJSA-N 0.000 description 1
- QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 description 1
- NLCDVZJDEXIDDL-BIIVOSGPSA-N Asn-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N)C(=O)O NLCDVZJDEXIDDL-BIIVOSGPSA-N 0.000 description 1
- KHCNTVRVAYCPQE-CIUDSAMLSA-N Asn-Lys-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O KHCNTVRVAYCPQE-CIUDSAMLSA-N 0.000 description 1
- NCXTYSVDWLAQGZ-ZKWXMUAHSA-N Asn-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O NCXTYSVDWLAQGZ-ZKWXMUAHSA-N 0.000 description 1
- PIABYSIYPGLLDQ-XVSYOHENSA-N Asn-Thr-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PIABYSIYPGLLDQ-XVSYOHENSA-N 0.000 description 1
- CELPEWWLSXMVPH-CIUDSAMLSA-N Asp-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O CELPEWWLSXMVPH-CIUDSAMLSA-N 0.000 description 1
- KHGPWGKPYHPOIK-QWRGUYRKSA-N Asp-Gly-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KHGPWGKPYHPOIK-QWRGUYRKSA-N 0.000 description 1
- CLUMZOKVGUWUFD-CIUDSAMLSA-N Asp-Leu-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O CLUMZOKVGUWUFD-CIUDSAMLSA-N 0.000 description 1
- YWLDTBBUHZJQHW-KKUMJFAQSA-N Asp-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N YWLDTBBUHZJQHW-KKUMJFAQSA-N 0.000 description 1
- UCHSVZYJKJLPHF-BZSNNMDCSA-N Asp-Phe-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O UCHSVZYJKJLPHF-BZSNNMDCSA-N 0.000 description 1
- RSMZEHCMIOKNMW-GSSVUCPTSA-N Asp-Thr-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RSMZEHCMIOKNMW-GSSVUCPTSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 244000146462 Centella asiatica Species 0.000 description 1
- 235000004032 Centella asiatica Nutrition 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 241000759833 Cornus officinalis Species 0.000 description 1
- HRJLVSQKBLZHSR-ZLUOBGJFSA-N Cys-Asn-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O HRJLVSQKBLZHSR-ZLUOBGJFSA-N 0.000 description 1
- JDHMXPSXWMPYQZ-AAEUAGOBSA-N Cys-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CS)N JDHMXPSXWMPYQZ-AAEUAGOBSA-N 0.000 description 1
- ZMWOJVAXTOUHAP-ZKWXMUAHSA-N Cys-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N ZMWOJVAXTOUHAP-ZKWXMUAHSA-N 0.000 description 1
- NDNZRWUDUMTITL-FXQIFTODSA-N Cys-Ser-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NDNZRWUDUMTITL-FXQIFTODSA-N 0.000 description 1
- VIOQRFNAZDMVLO-NRPADANISA-N Cys-Val-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VIOQRFNAZDMVLO-NRPADANISA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- HWEINOMSWQSJDC-SRVKXCTJSA-N Gln-Leu-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HWEINOMSWQSJDC-SRVKXCTJSA-N 0.000 description 1
- ARYKRXHBIPLULY-XKBZYTNZSA-N Gln-Thr-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ARYKRXHBIPLULY-XKBZYTNZSA-N 0.000 description 1
- ZZLDMBMFKZFQMU-NRPADANISA-N Gln-Val-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O ZZLDMBMFKZFQMU-NRPADANISA-N 0.000 description 1
- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
- HUWSBFYAGXCXKC-CIUDSAMLSA-N Glu-Ala-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O HUWSBFYAGXCXKC-CIUDSAMLSA-N 0.000 description 1
- HJIFPJUEOGZWRI-GUBZILKMSA-N Glu-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N HJIFPJUEOGZWRI-GUBZILKMSA-N 0.000 description 1
- SJPMNHCEWPTRBR-BQBZGAKWSA-N Glu-Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SJPMNHCEWPTRBR-BQBZGAKWSA-N 0.000 description 1
- ZWABFSSWTSAMQN-KBIXCLLPSA-N Glu-Ile-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O ZWABFSSWTSAMQN-KBIXCLLPSA-N 0.000 description 1
- ATVYZJGOZLVXDK-IUCAKERBSA-N Glu-Leu-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O ATVYZJGOZLVXDK-IUCAKERBSA-N 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- BFEZQZKEPRKKHV-SRVKXCTJSA-N Glu-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O BFEZQZKEPRKKHV-SRVKXCTJSA-N 0.000 description 1
- ZKONLKQGTNVAPR-DCAQKATOSA-N Glu-Pro-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)N ZKONLKQGTNVAPR-DCAQKATOSA-N 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- NZAFOTBEULLEQB-WDSKDSINSA-N Gly-Asn-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)CN NZAFOTBEULLEQB-WDSKDSINSA-N 0.000 description 1
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 1
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 1
- WCORRBXVISTKQL-WHFBIAKZSA-N Gly-Ser-Ser Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WCORRBXVISTKQL-WHFBIAKZSA-N 0.000 description 1
- HIAHVKLTHNOENC-HGNGGELXSA-N His-Glu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HIAHVKLTHNOENC-HGNGGELXSA-N 0.000 description 1
- PMWSGVRIMIFXQH-KKUMJFAQSA-N His-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)C1=CN=CN1 PMWSGVRIMIFXQH-KKUMJFAQSA-N 0.000 description 1
- YIGCZZKZFMNSIU-RWMBFGLXSA-N His-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N YIGCZZKZFMNSIU-RWMBFGLXSA-N 0.000 description 1
- ULRFSEJGSHYLQI-YESZJQIVSA-N His-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CN=CN3)N)C(=O)O ULRFSEJGSHYLQI-YESZJQIVSA-N 0.000 description 1
- YEKYGQZUBCRNGH-DCAQKATOSA-N His-Pro-Ser Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CN=CN2)N)C(=O)N[C@@H](CO)C(=O)O YEKYGQZUBCRNGH-DCAQKATOSA-N 0.000 description 1
- IXQGOKWTQPCIQM-YJRXYDGGSA-N His-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O IXQGOKWTQPCIQM-YJRXYDGGSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- WECYRWOMWSCWNX-XUXIUFHCSA-N Ile-Arg-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O WECYRWOMWSCWNX-XUXIUFHCSA-N 0.000 description 1
- NYEYYMLUABXDMC-NHCYSSNCSA-N Ile-Gly-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)O)N NYEYYMLUABXDMC-NHCYSSNCSA-N 0.000 description 1
- QZZIBQZLWBOOJH-PEDHHIEDSA-N Ile-Ile-Val Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)O QZZIBQZLWBOOJH-PEDHHIEDSA-N 0.000 description 1
- HPCFRQWLTRDGHT-AJNGGQMLSA-N Ile-Leu-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O HPCFRQWLTRDGHT-AJNGGQMLSA-N 0.000 description 1
- CZWANIQKACCEKW-CYDGBPFRSA-N Ile-Pro-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)O)N CZWANIQKACCEKW-CYDGBPFRSA-N 0.000 description 1
- YKZAMJXNJUWFIK-JBDRJPRFSA-N Ile-Ser-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)O)N YKZAMJXNJUWFIK-JBDRJPRFSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 1
- YKNBJXOJTURHCU-DCAQKATOSA-N Leu-Asp-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKNBJXOJTURHCU-DCAQKATOSA-N 0.000 description 1
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 1
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 1
- QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 description 1
- HQUXQAMSWFIRET-AVGNSLFASA-N Leu-Glu-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HQUXQAMSWFIRET-AVGNSLFASA-N 0.000 description 1
- WQWSMEOYXJTFRU-GUBZILKMSA-N Leu-Glu-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O WQWSMEOYXJTFRU-GUBZILKMSA-N 0.000 description 1
- ZFNLIDNJUWNIJL-WDCWCFNPSA-N Leu-Glu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZFNLIDNJUWNIJL-WDCWCFNPSA-N 0.000 description 1
- HYIFFZAQXPUEAU-QWRGUYRKSA-N Leu-Gly-Leu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C HYIFFZAQXPUEAU-QWRGUYRKSA-N 0.000 description 1
- KUIDCYNIEJBZBU-AJNGGQMLSA-N Leu-Ile-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O KUIDCYNIEJBZBU-AJNGGQMLSA-N 0.000 description 1
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 1
- BJWKOATWNQJPSK-SRVKXCTJSA-N Leu-Met-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N BJWKOATWNQJPSK-SRVKXCTJSA-N 0.000 description 1
- YESNGRDJQWDYLH-KKUMJFAQSA-N Leu-Phe-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)O)N YESNGRDJQWDYLH-KKUMJFAQSA-N 0.000 description 1
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 1
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 1
- LCNASHSOFMRYFO-WDCWCFNPSA-N Leu-Thr-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O LCNASHSOFMRYFO-WDCWCFNPSA-N 0.000 description 1
- FGZVGOAAROXFAB-IXOXFDKPSA-N Leu-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(C)C)N)O FGZVGOAAROXFAB-IXOXFDKPSA-N 0.000 description 1
- RNYLNYTYMXACRI-VFAJRCTISA-N Leu-Thr-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O RNYLNYTYMXACRI-VFAJRCTISA-N 0.000 description 1
- HQBOMRTVKVKFMN-WDSOQIARSA-N Leu-Trp-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C(C)C)C(O)=O HQBOMRTVKVKFMN-WDSOQIARSA-N 0.000 description 1
- WQWZXKWOEVSGQM-DCAQKATOSA-N Lys-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN WQWZXKWOEVSGQM-DCAQKATOSA-N 0.000 description 1
- ALSRJRIWBNENFY-DCAQKATOSA-N Lys-Arg-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O ALSRJRIWBNENFY-DCAQKATOSA-N 0.000 description 1
- WVJNGSFKBKOKRV-AJNGGQMLSA-N Lys-Leu-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WVJNGSFKBKOKRV-AJNGGQMLSA-N 0.000 description 1
- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 1
- MIFFFXHMAHFACR-KATARQTJSA-N Lys-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN MIFFFXHMAHFACR-KATARQTJSA-N 0.000 description 1
- FWTBMGAKKPSTBT-GUBZILKMSA-N Met-Gln-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FWTBMGAKKPSTBT-GUBZILKMSA-N 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 1
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 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
- RIYZXJVARWJLKS-KKUMJFAQSA-N Phe-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 RIYZXJVARWJLKS-KKUMJFAQSA-N 0.000 description 1
- BIYWZVCPZIFGPY-QWRGUYRKSA-N Phe-Gly-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O BIYWZVCPZIFGPY-QWRGUYRKSA-N 0.000 description 1
- GYEPCBNTTRORKW-PCBIJLKTSA-N Phe-Ile-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O GYEPCBNTTRORKW-PCBIJLKTSA-N 0.000 description 1
- TXKWKTWYTIAZSV-KKUMJFAQSA-N Phe-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N TXKWKTWYTIAZSV-KKUMJFAQSA-N 0.000 description 1
- OQTDZEJJWWAGJT-KKUMJFAQSA-N Phe-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O OQTDZEJJWWAGJT-KKUMJFAQSA-N 0.000 description 1
- AXIOGMQCDYVTNY-ACRUOGEOSA-N Phe-Phe-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 AXIOGMQCDYVTNY-ACRUOGEOSA-N 0.000 description 1
- IEIFEYBAYFSRBQ-IHRRRGAJSA-N Phe-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IEIFEYBAYFSRBQ-IHRRRGAJSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- LCRSGSIRKLXZMZ-BPNCWPANSA-N Pro-Ala-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LCRSGSIRKLXZMZ-BPNCWPANSA-N 0.000 description 1
- SGCZFWSQERRKBD-BQBZGAKWSA-N Pro-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 SGCZFWSQERRKBD-BQBZGAKWSA-N 0.000 description 1
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 1
- BRJGUPWVFXKBQI-XUXIUFHCSA-N Pro-Leu-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRJGUPWVFXKBQI-XUXIUFHCSA-N 0.000 description 1
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 1
- CPRLKHJUFAXVTD-ULQDDVLXSA-N Pro-Leu-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CPRLKHJUFAXVTD-ULQDDVLXSA-N 0.000 description 1
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- SEZGGSHLMROBFX-CIUDSAMLSA-N Pro-Ser-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O SEZGGSHLMROBFX-CIUDSAMLSA-N 0.000 description 1
- KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 1
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 1
- DLZBBDSPTJBOOD-BPNCWPANSA-N Pro-Tyr-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O DLZBBDSPTJBOOD-BPNCWPANSA-N 0.000 description 1
- VDHGTOHMHHQSKG-JYJNAYRXSA-N Pro-Val-Phe Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O VDHGTOHMHHQSKG-JYJNAYRXSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- GYXVUTAOICLGKJ-ACZMJKKPSA-N Ser-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N GYXVUTAOICLGKJ-ACZMJKKPSA-N 0.000 description 1
- UOLGINIHBRIECN-FXQIFTODSA-N Ser-Glu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UOLGINIHBRIECN-FXQIFTODSA-N 0.000 description 1
- HBTCFCHYALPXME-HTFCKZLJSA-N Ser-Ile-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HBTCFCHYALPXME-HTFCKZLJSA-N 0.000 description 1
- UIPXCLNLUUAMJU-JBDRJPRFSA-N Ser-Ile-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UIPXCLNLUUAMJU-JBDRJPRFSA-N 0.000 description 1
- DOSZISJPMCYEHT-NAKRPEOUSA-N Ser-Ile-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O DOSZISJPMCYEHT-NAKRPEOUSA-N 0.000 description 1
- VZQRNAYURWAEFE-KKUMJFAQSA-N Ser-Leu-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VZQRNAYURWAEFE-KKUMJFAQSA-N 0.000 description 1
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 1
- GVMUJUPXFQFBBZ-GUBZILKMSA-N Ser-Lys-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GVMUJUPXFQFBBZ-GUBZILKMSA-N 0.000 description 1
- ASGYVPAVFNDZMA-GUBZILKMSA-N Ser-Met-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)N ASGYVPAVFNDZMA-GUBZILKMSA-N 0.000 description 1
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- LXWZOMSOUAMOIA-JIOCBJNQSA-N Thr-Asn-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O LXWZOMSOUAMOIA-JIOCBJNQSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- CRZNCABIJLRFKZ-IUKAMOBKSA-N Thr-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N CRZNCABIJLRFKZ-IUKAMOBKSA-N 0.000 description 1
- SCSVNSNWUTYSFO-WDCWCFNPSA-N Thr-Lys-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O SCSVNSNWUTYSFO-WDCWCFNPSA-N 0.000 description 1
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 1
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 1
- CURFABYITJVKEW-QTKMDUPCSA-N Thr-Val-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O CURFABYITJVKEW-QTKMDUPCSA-N 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 241001197778 Tripterygium hypoglaucum Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- VZBWRZGNEPBRDE-HZUKXOBISA-N Trp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N VZBWRZGNEPBRDE-HZUKXOBISA-N 0.000 description 1
- DLZKEQQWXODGGZ-KWQFWETISA-N Tyr-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DLZKEQQWXODGGZ-KWQFWETISA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 1
- VJOWWOGRNXRQMF-UVBJJODRSA-N Val-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 VJOWWOGRNXRQMF-UVBJJODRSA-N 0.000 description 1
- UUYCNAXCCDNULB-QXEWZRGKSA-N Val-Arg-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O UUYCNAXCCDNULB-QXEWZRGKSA-N 0.000 description 1
- CWSIBTLMMQLPPZ-FXQIFTODSA-N Val-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N CWSIBTLMMQLPPZ-FXQIFTODSA-N 0.000 description 1
- PFMAFMPJJSHNDW-ZKWXMUAHSA-N Val-Cys-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N PFMAFMPJJSHNDW-ZKWXMUAHSA-N 0.000 description 1
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 1
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 1
- ZIGZPYJXIWLQFC-QTKMDUPCSA-N Val-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)N)O ZIGZPYJXIWLQFC-QTKMDUPCSA-N 0.000 description 1
- FEXILLGKGGTLRI-NHCYSSNCSA-N Val-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N FEXILLGKGGTLRI-NHCYSSNCSA-N 0.000 description 1
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 1
- UJMCYJKPDFQLHX-XGEHTFHBSA-N Val-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N)O UJMCYJKPDFQLHX-XGEHTFHBSA-N 0.000 description 1
- PQSNETRGCRUOGP-KKHAAJSZSA-N Val-Thr-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(N)=O PQSNETRGCRUOGP-KKHAAJSZSA-N 0.000 description 1
- TVGWMCTYUFBXAP-QTKMDUPCSA-N Val-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N)O TVGWMCTYUFBXAP-QTKMDUPCSA-N 0.000 description 1
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 108010045023 alanyl-prolyl-tyrosine Proteins 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 239000003936 androgen receptor antagonist Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 201000007983 brain glioma Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 125000000567 diterpene group Chemical group 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 108010040030 histidinoalanine Proteins 0.000 description 1
- 108010028295 histidylhistidine Proteins 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
- 235000009408 lignans Nutrition 0.000 description 1
- 150000005692 lignans Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 238000012257 pre-denaturation Methods 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010084932 tryptophyl-proline Proteins 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 108010005834 tyrosyl-alanyl-glycine Proteins 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/04—Oxygen as only ring hetero atoms containing a five-membered hetero ring, e.g. griseofulvin, vitamin C
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/44—Preparation of O-glycosides, e.g. glucosides
- C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
本发明涉及一种雷酚内酯苷类化合物,所述雷酚内酯苷类化合物可以通过酶促法生产,将雷酚内酯苷与糖苷供体在适合糖基转移酶的条件下进行反应,并分离酶促反应后的产物可以得到本发明所述雷酚内酯苷。本发明所述雷酚内酯苷可用于预防或治疗炎症类疾病,并具有抗肿瘤的作用。
Description
技术领域
本发明属于医药技术领域,具体涉及一种雷酚内酯苷类化合物及其应用。
背景技术
雷公藤(Tripterygium wilfordii)系卫矛科植物,作为传统中药,它被运用于多种疾病的 治疗已有相当长的历史。主要分布于我国长江流域以南山区和北长白山区。雷公藤作为一种 传统中药在我国已有几千年的药用历史。作为药物,雷公藤主要用于治疗类风湿性关节炎和 某些皮肤病。自上世纪60年代开始雷公藤制剂用于治疗炎症、癌症、麻风病、慢性肾炎、系 统性红斑狼疮等疾病。雷公藤主要含有倍半萜、二萜、三萜化合物及少量木脂素和其它成分。
雷酚内酯(Triptophenolide)是一种二萜类化合物,主要存在于卫矛科植物中,如昆明山 海棠、雷公藤的根皮和心木。现代药理研究表明,雷酚内酯具有具有抗炎免疫作用外也能作 为雄激素受体拮抗剂,雷酚内酯对列腺癌细胞有一定的抑制作用。但是雷酚内酯水溶性差, 对雷酚内酯进行葡萄糖糖基化后能显著提高雷酚内酯水溶性,更有利于雷酚内酯成药。雷酚 内酯在细胞培养基中溶解性差,雷酚内酯糖基化后形成的雷酚内酯苷可以溶解于细胞培养基。
发明内容
本发明涉及一种雷酚内酯苷类化合物,所述化合物具有如下结构式:
其中,R为糖基。
进一步地,所述糖基选自葡萄糖基或葡萄糖醛酸基。
在一个具体的实施方案中,本发明提供了一种具有如下结构式的雷酚内酯苷:
本发明另一方面,提供了本发明所述化合物在制备具有抗炎、免疫调节和抗肿瘤药物中 的运用。
本发明的又一方面,提供了一种包含本发明所述化合物的组合物,所述组合物通过将其 它抗炎、免疫调节或抗肿瘤药物与所述雷酚内酯苷类化合物联合使用,以达到联合用药的目 的。
本发明的再一方面,提供了一种包含本发明所述雷酚内酯苷类化合物的药物制剂,所述 药物制剂还含有制药上可接受的赋形剂,适合的剂型可以是口服制剂,如口服固体制剂或口 服液体制剂,或注射剂、或乳剂。
本发明的再一方面,提供了本发明所述雷酚内酯类化合物或包含本发明所述雷酚内酯类 化合物的组合物,在制备具有抗炎、免疫调剂或抗肿瘤药物中的运用。本发明药理实验表明 雷酚内酯苷可以抑制脑胶质瘤细胞,乳腺癌细胞,宫颈癌细胞,人类红白血病细胞的生长。
本发明的还一方面,提供了一种制备本发明所述雷酚内酯类化合物的方法,所述方法包 括:在适于酶促反应的条件下,使糖基供体和雷酚内酯与糖基转移酶进行反应,从而将糖基 供体转移到雷酚内酯的羟基上,分离纯化酶催化产物得到雷酚内酯苷化合物,所述糖基转移 酶为氧糖基转移酶。
一个具体的糖基转移酶是雷公藤糖基转移酶TwUGTE1,因此,本发明的一个实施方案 中,提供了一种一种获取雷公藤糖基转移酶的方法,通过构建雷公藤糖基转移酶基因,并将 转移转入宿主细胞中,在培养基中发酵表达并纯化表达所获得的蛋白,即获得雷公藤糖基转 移酶。
所述雷公藤糖基转移酶具有SEQ ID NO:2所述氨基酸序列,编码所述雷公藤转移酶的 雷公藤糖基转移酶基因TwUGPT1的核苷酸序列如SEQ ID NO:1所示。
所述糖基供体为尿苷二磷酸糖基转移酶,优选为UDP-葡萄糖或UDP-葡糖醛酸,所述纯 化产物雷酚内酯苷的方法为高效液相色谱法。
附图说明
图1为雷酚内酯苷的质谱图。
图2为雷酚内酯苷的核磁氢谱图。
图3为雷酚内酯苷的核磁碳谱图。
图4为雷酚内酯苷的HMBC谱图。
图5为雷酚内酯苷的COSY谱图。
图6为雷酚内酯苷的HMQC谱图。
图7为雷酚内酯苷不同给药浓度下不同细胞存活率曲线图。
图8为在MCF-7细胞中雷酚内酯和雷酚内酯苷水溶性的比较(Control为对照试验未加药 物,Trip为在培养基中加入雷酚内酯;Trip-side为在培养基中加入雷酚内酯苷;在雷酚内酯的 浓度为50μM时,在培养基中已出现结晶;雷酚内酯苷的浓度为800μM时,培养基中无结 晶出现)。
具体实施方式
以下通过优选实施例并结合附图具体说明本发明的各个方面和特征,本领域的技术人员 应该理解,这些实施例只是用于说明,而不是限制本发明的范围。在不背离权利要求书范围 的条件下,本领域的技术人员可以对本发明的各个方面进行各种修改和改进,这些修改和改 进也属于本发明的保护范围。例如,将实施例中所实用的启动子和表达载体替换为本领域中 常用的其它启动子和表达载体,是本领域的普通技术人员所能够理解并实现的。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
下述实施例中的雷公藤(Tripterygium wilfordii Hook.f.)悬浮细胞在文献“雷公藤4-(5’-二 磷酸胞苷)-2-C-甲基-D-赤藓醇激酶基因的全长克隆与表达分析.中国中药杂志,2015,40(21): 4165-4170”中公开过,公众可从首都医科大学分子生药与中药资源实验室获得。
实施例1构建雷公藤糖基转移酶编码基因TwUGPT1并表达获得TwUGPT1
1、雷公藤悬浮细胞总RNA提取及cDNA第一链的获得
取雷公藤悬浮细胞,迅速放于液氮中,-80℃低温保存备用,用于提取RNA,提取方法 按照总RNA提取试剂盒(上海普罗麦格生物产品有限公司)操作说明书进行;并利用FastKing cDNA第一链合成试剂盒(天根生化科技北京有限公司)进行反转录获得cDNA。
2、引物设计及PCR扩增
根据雷公藤转录组数据注释筛选得到基因全长序列片段,利用Primer5设计特异性引物 TwUGTE1-R和TwUGTE1-F引物,将设计的引物送睿博生物技术有限公司合成,-20℃保存, 引物序列如下:
TwUGTE1-R CCACATCACTCAACGTAGTACATAC(ID NO:3)
TwUGTE1-F CTACCTTATCCTAATTCACGCTTAC(ID NO:4)
参照KAPAHIFI高保真酶(北京普凯瑞生物科技有限公司)的扩增方法克隆目标序列的 全长基因,反应体系如下:
反应程序:98℃预变性3min;98℃变性20s,53℃退火15s,72℃延伸2min为一个 循环,共计35个循环,最后72℃再延伸7min;取PCR产物5μL代替cDNA,利用上述反 应体系进行二次扩增。PCR反应结束后,进行1%琼脂糖凝胶电泳检测;PCR反应结束后, 进行1%琼脂糖凝胶电泳,160V电压,电泳30min。目的条带用胶回收试剂盒(Thermo公司) 的方法切胶回收。
3、连接克隆载体,转化感受态细胞,筛选阳性克隆并测序
将质量浓度符合要求的PCR产物连接到pEASY-Blunt Zero载体(北京全式金生物技术有 限公司)上,连接体系如下:
将添加好的反应体系在30℃放置15min进行连接,连接产物放置在冰上,转化到TransT1 大肠杆菌感受态细胞(北京全式金生物技术有限公司)中,转化过程如下:
(1)连接好的载体加入到TransT1感受态细胞中,冰上放置30min;
(2)42℃热激30s,取出放冰上2min;
(3)添加液体LB培养基500μL,37℃的摇床上180r/min震荡培养1h,在含氨苄抗性的 固体培养基上37℃培养过夜,挑选单菌落送睿博生物科技有限公司完成测序。
4、将基因TwUGTE1构建到Paml-c2x表达载体中
将测序结果正确的菌株和Pmal-c2x载体菌株分别接种到含相应抗性的液体LB培养基中, 37℃、220r/min下震荡培养12~16h,用质粒小提试剂盒(天根生化科技北京有限公司)提取 质粒。
设计目的基因特异性的引物,送睿博兴科生物技术有限公司合成。
F:CGCGGATCCATGCAGGAGGACAAATTCACATATT(ID NO:5)
R:TGCACTGCAGCTTCCATTGCTCGACTAGCTTGGCC(ID NO:6)
以测序正确的质粒为模板,用高保真酶扩增得到插入片段扩增产物。
PCR反应结束后,进行1%琼脂糖凝胶电泳,160V电压,电泳30min。目的条带用胶回收试剂盒(Thermo公司)的方法切胶回收,利用Genova Nano三合一超微量分光光度计测 定回收TwUGTE1基因的浓度。
将载体Pmal-c2x和TwUGTE1基因分别用BamH I和Pst I HF限制性内切酶进行双酶切, 酶切体系如下:
37℃水浴酶切2h,2%琼脂糖凝胶电泳,目的条带用胶回收试剂盒(Thermo公司)的方 法切胶回收。
于冰水浴中配制重组反应体系,反应体系如下:
重组反应体系克隆载体使用量为0.018pmol;最适克隆载体与插入片段摩尔比为1:2,即 最适插入片段使用量约为0.036pmol。
体系配制完成后,用移液器上下轻轻吹打几次混匀各组分,50℃反应15min,待反应完 成后,立即将反应管置于冰水浴中冷却5min,之后,将反应产物进行转化到TransT1大肠杆 菌感受态细胞中在含氨苄抗性的固体培养基上37℃培养过夜,挑选单菌落送睿博兴科生物科 技有限公司完成测序。测序结果正确的菌株接种至50mL含有100mg/L氨苄西林的LB培养 基中培养过夜,质粒小提试剂盒(天根生化科技北京有限公司)提取质粒,质粒存放于-20℃ 冰箱保存。
5、重组大肠杆菌制备、酶的发酵表达及纯化
Pmal-C2X-TwUGTE1转化到BL21(DE3)大肠杆菌(北京全式金生物技术有限公司)表达 感受态细胞中,转化过程按说明书操作。
蛋白诱导表达:
(1)将重组质粒与空载体pMAL-c2X分别转化到大肠杆菌表达型感受态细胞BL21(DE3),选 取阳性单克隆菌落37℃,250r·min-1摇14h后,按1.5‰的比例各扩大培养200mL,37℃摇 到OD600约为0.6-0.8后,加入异丙基硫代半乳糖苷(IPTG)至终浓度1mM,低温16℃诱导表 达18h。
(2)低温诱导的菌液4℃10000×g离心3min收集菌体,Resuspension buffer 5mL重悬。
(3)加入Chicken white lysozyme(50mg·mL-1),于重悬菌体中,至0.5mg·mL-1,混均,冰上静 置20min。
(4)加入10%Triton X-100至终浓度0.1%。加入1/10体积的5mol·L-1NaCl溶液,超声破 碎30min(超声5s,暂停5s),4℃、12 000×g离心30min。
(5)取1mL的Amylose Resin加入到柱子中,Amylose Resin事先用5倍柱体积Washbuffer 清洗。
(6)将破碎的菌液上清加到含有Amylose Resin的15mL离心管中,小摇床高转速冰上晃动 2h。
(7)加入15倍柱体积Wash buffer清洗后再用15倍柱体积Resuspension buffer清洗。
(8)加入1倍柱体积Elution buffer A洗脱一次。加入两倍柱体积Elution bufferB,4℃摇晃10 min后洗脱,重复两次。
(9)将Elution buffer B洗脱液分别用10KD和30KD的超滤管浓缩空载对照蛋白和糖基转 移酶融合蛋白,浓缩蛋白于-80℃保存。
实施例2利用TwUGPT1催化合成雷酚内酯苷
(1)挑取含有重组质粒pMALc2XTwUGTE1单个阳性克隆E.coli BL21(DE3)菌落接种于 10mL的LB液体培养基(含100mg·L-1氨苄青霉素)中,37℃,250r·min-1培养过夜。
(2)按1‰的比例各扩大培养至10L,37℃250r·min-1摇至OD600约为0.6-0.8后,加入异丙基硫代半乳糖苷(IPTG)至终浓度1mM,低温16℃诱导表达20h。
(3)低温诱导的菌液在高速离心机中离心3min(4℃,10000g)收集菌体,弃去培养基。蒸馏水清洗后重悬于300mL含有1mM DTT的Tris-HCl(100mM,pH=8.0)缓冲液中。
(4)利用ATS匀质机高压破碎重悬菌液,破碎30min。将破碎菌体于高速离心机中离心20min(4℃,10000g)收集上清液。
(5)300mL上清液中加入UDPG至终浓度为1mM和雷酚内酯至终浓度为100μM,40℃水浴中反应24h。
(6)反应液用等体积的乙酸乙酯萃取6次,将萃取液减压蒸发除去乙酸乙酯,用10mL 甲醇溶解产物。过0.22μm滤膜后,按1.2.11步骤制备雷酚内酯苷,重复制备反应多次。液相 色谱串联高分辨质谱检测反应产物。将雷酚内酯苷溶解于0.5mL氘代DMSO至终浓度约为6 mg·mL-1,利用800M核磁测雷酚内酯苷的1H-NMR、13C-NMR、HMBC、HMQC、COSY谱 图,以确定雷酚内酯苷的结构。
制备色谱条件:仪器:安捷伦制备液相(Agilent 1260);流动相A:水;流动相B:乙腈; 10mL·min-1;进样量5mL;色谱柱:Waters C18OBD(19×50mm,5μm);检测波长:210nm;0-10min:95%(A)-70%(A);20-22min:70%(A)-60%(A);32-35min:60%(A)-40%(A);45min:35%(A)。收集25.5min处的馏分,减压旋蒸除去水和乙腈,准确称量生成雷酚内酯苷的质量。
[M+CF3COOH]+m/z:587.21.
1H-NMR(800MHz,DMSO d_6),7.160(d,J=8Hz,1H),7.094(d,J=8Hz,1H),4.842-4.921(m, 2H),4.482(d,J=8Hz,1H),3.701(m,1H),3.623-3.640(m,1H),3.430(m,1H),3.280(m,1H), 3.217(m,1H),3.150(m,1H),3.130(m,1H),3.017(m,1H),2.993(s,br,1H),2.973(m,1H), 2.486(m,1H),2.334(m,1H),2.237(m,1H),1.090(m,1H),1.737(m,1H),1.588-1.610(m,1H), 1.137(d,J=6.4Hz,3H),1.070(d,J=7.2Hz,3H),0.941(s,3H).
13C-NMR(800MHz,DMSO d_6),174.084,164.946,152.094,144.394,139.992,129.629, 123.985,123.353,120.921,105.093,77.457,76.885,74.579,70.985,70.458,61.615,42.586, 36.344,32.563,25.245,24.729,24.050,23.166,22.178,19.520,18.219.
其它位置的连接均通过综合解析2D-NMR包括图4的HMBC、图5的HMBC和图6的 H-HCOSY得以确定,因此鉴定化合物为雷酚内酯-6-O-β-D-葡萄糖苷(雷酚内酯苷)
实施例3雷酚内酯苷的活性检测实验
1.细胞培养:将U251、U87MG、C6、A549、MCF-7、HepG2、PANC-1、Hela、K562、 RBL-2H3、LO2、HEK293、Astroglia细胞在37℃、含有5%CO2和一定湿度的细胞培养箱中 培养H,所用培养基为含10%胎牛血清、2mML--谷氨酰胺、100μg/mL链霉素、100U/mL青霉 素的MEM或DMEM培养基。每天观察细胞状态和密度,平均每2天更换新鲜培养基1次,3 天传代1次。
2.96孔板,铺板数3000-10000个细胞/孔,培养24h后加入不同浓度的药物,继续培养 24h和48h后用Cell Counting Kit-8试剂盒(日本同仁)检测细胞的活性,按说明书30min-4h 之间完成检测,计算IC50(表1)。
3.水溶性比较:在MCF-7细胞中加入不同浓度药物24h后,显微镜下拍照,比例尺:200μm。
4.药物四个浓度:12.5,50,200,800μM,结果见下表。
表1不同肿瘤细胞的IC50
序列表
<110> 首都医科大学
<120> 雷酚内酯苷类化合物及其应用
<141> 2018-05-29
<160> 6
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1476
<212> DNA
<213> 雷公藤(Tripterygium wilfordii)
<400> 1
atgcaggagg acaaattcac atattcacac acacacagag aagtttcaat ggctgccata 60
gttctgtatc caactacagg tatgggccac ctcatatcca tggtagagtt gggcaagctc 120
atactcactc accacccatc tttcaccgtc aacatcctcc tccccacagc tccctacgcc 180
actggctcta ctgctcaata catttctgcc gtctccacca caaacccatc tatcatcttc 240
caccaccttc cccctgtttc tctccctcta gaccctgcct cttattcctg tgtcgaagcc 300
ctcacgttcg acctcattcg cctcaacaac cccaacgtcc acactgcaat ccaatcaatt 360
tctcaaacat ccaccgtcca tgccttaatc ctggactttt tttgtaatgc ggctcttgat 420
gttgctacag aacttgatgt tccagcttac tttttcctta cttctggtgc tagttttcta 480
gctctgtttt gtcactttcc aacaattgac agaagcacca ataagaattt caaggatctc 540
gagactactg ttaacctccc ttacttgcca ccgataccct tgtctcatat gccagagcca 600
atgcttgaaa aagacacaac agagtatgct ggcttcattg attgctcagt tggtttgagt 660
aaatcaaccg gaatcatcgt taacacgttt agcactctcg aaccaaaagc tgtgaaggcc 720
ttggcagatg gagtttgcaa tcctgatggt ccaacaccgc cagttttctg cattggacca 780
ctaattgtca caaatcgtca aatcggtaat gagggtgatg ataaggtgct tggatctgaa 840
tgcttaactt ggctcgacaa gcaaccaagt caaagcatag tatttttgtg ttttggtagc 900
ttgggcttgc tttctaagga acagttgagg gaaatagcta ttggtttgga gaagagtggc 960
caaaggttct tgtgggtggt acggaaccca ccttcggagg acaaaaagca gaggttcctc 1020
actcaaccag acccagatct gaattctttg ttctctgatg gtttcttgga ccgtacaaag 1080
gagagaggac tggtagttaa gcggtgggca ccacaggtgg cagtgttaaa tcatgaagca 1140
gttggagggt tcgtgactca ctgtggctgg aactcagttt tggaatcggt ttgtgcaggt 1200
ataccaatgg ttgcatggcc gttatacgca gaacaaaagt ttaacaaggc attgctggtt 1260
gaggagctga agctggcttt gccaatgaac gagtccgaaa ctgggttcgt tagtgcaacc 1320
gaggttgaga agcgagttag agaattgatg gagtcggagg aaggtaactc attgagggaa 1380
cgagtaacgg caaagagaaa tgaagcaatg aaggctatgg aagagggtgg atcatccagg 1440
gttgcattgg ccaagctagt cgagcaatgg aagtaa 1476
<210> 2
<211> 491
<212> PRT
<213> 雷公藤(Tripterygium wilfordii)
<400> 2
Met Gln Glu Asp Lys Phe Thr Tyr Ser His Thr His Arg Glu Val Ser
1 5 10 15
Met Ala Ala Ile Val Leu Tyr Pro Thr Thr Gly Met Gly His Leu Ile
20 25 30
Ser Met Val Glu Leu Gly Lys Leu Ile Leu Thr His His Pro Ser Phe
35 40 45
Thr Val Asn Ile Leu Leu Pro Thr Ala Pro Tyr Ala Thr Gly Ser Thr
50 55 60
Ala Gln Tyr Ile Ser Ala Val Ser Thr Thr Asn Pro Ser Ile Ile Phe
65 70 75 80
His His Leu Pro Pro Val Ser Leu Pro Leu Asp Pro Ala Ser Tyr Ser
85 90 95
Cys Val Glu Ala Leu Thr Phe Asp Leu Ile Arg Leu Asn Asn Pro Asn
100 105 110
Val His Thr Ala Ile Gln Ser Ile Ser Gln Thr Ser Thr Val His Ala
115 120 125
Leu Ile Leu Asp Phe Phe Cys Asn Ala Ala Leu Asp Val Ala Thr Glu
130 135 140
Leu Asp Val Pro Ala Tyr Phe Phe Leu Thr Ser Gly Ala Ser Phe Leu
145 150 155 160
Ala Leu Phe Cys His Phe Pro Thr Ile Asp Arg Ser Thr Asn Lys Asn
165 170 175
Phe Lys Asp Leu Glu Thr Thr Val Asn Leu Pro Tyr Leu Pro Pro Ile
180 185 190
Pro Leu Ser His Met Pro Glu Pro Met Leu Glu Lys Asp Thr Thr Glu
195 200 205
Tyr Ala Gly Phe Ile Asp Cys Ser Val Gly Leu Ser Lys Ser Thr Gly
210 215 220
Ile Ile Val Asn Thr Phe Ser Thr Leu Glu Pro Lys Ala Val Lys Ala
225 230 235 240
Leu Ala Asp Gly Val Cys Asn Pro Asp Gly Pro Thr Pro Pro Val Phe
245 250 255
Cys Ile Gly Pro Leu Ile Val Thr Asn Arg Gln Ile Gly Asn Glu Gly
260 265 270
Asp Asp Lys Val Leu Gly Ser Glu Cys Leu Thr Trp Leu Asp Lys Gln
275 280 285
Pro Ser Gln Ser Ile Val Phe Leu Cys Phe Gly Ser Leu Gly Leu Leu
290 295 300
Ser Lys Glu Gln Leu Arg Glu Ile Ala Ile Gly Leu Glu Lys Ser Gly
305 310 315 320
Gln Arg Phe Leu Trp Val Val Arg Asn Pro Pro Ser Glu Asp Lys Lys
325 330 335
Gln Arg Phe Leu Thr Gln Pro Asp Pro Asp Leu Asn Ser Leu Phe Ser
340 345 350
Asp Gly Phe Leu Asp Arg Thr Lys Glu Arg Gly Leu Val Val Lys Arg
355 360 365
Trp Ala Pro Gln Val Ala Val Leu Asn His Glu Ala Val Gly Gly Phe
370 375 380
Val Thr His Cys Gly Trp Asn Ser Val Leu Glu Ser Val Cys Ala Gly
385 390 395 400
Ile Pro Met Val Ala Trp Pro Leu Tyr Ala Glu Gln Lys Phe Asn Lys
405 410 415
Ala Leu Leu Val Glu Glu Leu Lys Leu Ala Leu Pro Met Asn Glu Ser
420 425 430
Glu Thr Gly Phe Val Ser Ala Thr Glu Val Glu Lys Arg Val Arg Glu
435 440 445
Leu Met Glu Ser Glu Glu Gly Asn Ser Leu Arg Glu Arg Val Thr Ala
450 455 460
Lys Arg Asn Glu Ala Met Lys Ala Met Glu Glu Gly Gly Ser Ser Arg
465 470 475 480
Val Ala Leu Ala Lys Leu Val Glu Gln Trp Lys
485 490
<210> 3
<211> 25
<212> DNA
<213> 人工序列()
<400> 3
ccacatcact caacgtagta catac 25
<210> 4
<211> 25
<212> DNA
<213> 人工序列()
<400> 4
ctaccttatc ctaattcacg cttac 25
<210> 5
<211> 34
<212> DNA
<213> 人工序列()
<400> 5
cgcggatcca tgcaggagga caaattcaca tatt 34
<210> 6
<211> 35
<212> DNA
<213> 人工序列()
<400> 6
tgcactgcag cttccattgc tcgactagct tggcc 35
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810526970.3A CN108948109B (zh) | 2018-05-29 | 2018-05-29 | 雷酚内酯苷类化合物及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810526970.3A CN108948109B (zh) | 2018-05-29 | 2018-05-29 | 雷酚内酯苷类化合物及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108948109A CN108948109A (zh) | 2018-12-07 |
CN108948109B true CN108948109B (zh) | 2020-08-11 |
Family
ID=64492098
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810526970.3A Active CN108948109B (zh) | 2018-05-29 | 2018-05-29 | 雷酚内酯苷类化合物及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108948109B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114807159B (zh) * | 2021-12-23 | 2023-09-29 | 西藏自治区农牧科学院农业研究所 | 一种与耐旱性相关的c-糖基黄酮代谢基因及其用途 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102875501A (zh) * | 2012-09-27 | 2013-01-16 | 南京泽朗农业发展有限公司 | 一种雷酚内酯的制备方法 |
CN105497045A (zh) * | 2015-12-17 | 2016-04-20 | 中国医学科学院医药生物技术研究所 | 雷酚内酯作为雄激素受体拮抗剂的应用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102924411B (zh) * | 2012-11-14 | 2016-08-17 | 兰州大学 | 雷公藤内酯醇中间体的合成方法 |
-
2018
- 2018-05-29 CN CN201810526970.3A patent/CN108948109B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102875501A (zh) * | 2012-09-27 | 2013-01-16 | 南京泽朗农业发展有限公司 | 一种雷酚内酯的制备方法 |
CN105497045A (zh) * | 2015-12-17 | 2016-04-20 | 中国医学科学院医药生物技术研究所 | 雷酚内酯作为雄激素受体拮抗剂的应用 |
Non-Patent Citations (4)
Title |
---|
OXIDATION AND GLUCOSE CONJUGATION OF SYNTHETIC ABIETANE DITERPENES BY CUNNINGHAMELLLA SP.II. NOVEL ROUTES TO THE FAMILY OF DITERPENES FROM TRIPTERYGIUM WILFORDII;R.Milanova et al.;《Journal of Natural Products》;19950131;第58卷(第1期);第68-73页 * |
R.Milanova et al..OXIDATION AND GLUCOSE CONJUGATION OF SYNTHETIC ABIETANE DITERPENES BY CUNNINGHAMELLLA SP.II. NOVEL ROUTES TO THE FAMILY OF DITERPENES FROM TRIPTERYGIUM WILFORDII.《Journal of Natural Products》.1995,第58卷(第1期),第68-73页. * |
R.Milanova et al..The optimization of tritoquinone production by Cunninghamella elegans using factorial design.《Enzyme and Microbial Technology》.1996,第19卷第86-93页. * |
The optimization of tritoquinone production by Cunninghamella elegans using factorial design;R.Milanova et al.;《Enzyme and Microbial Technology》;19961231;第19卷;第86-93页 * |
Also Published As
Publication number | Publication date |
---|---|
CN108948109A (zh) | 2018-12-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107058446B (zh) | 一组糖基转移酶及其应用 | |
CN110343678B (zh) | 一种珠子参糖基转移酶UGTPjm1基因及在制备人参皂苷Ro上的应用 | |
CN104357418A (zh) | 一种糖基转移酶及其突变体在合成人参皂苷Rh2中的应用 | |
Zhang et al. | Two new cytotoxic C-21 steroidal glycosides from the root of Cynanchum auriculatum | |
Xia et al. | Withapubesides A–D: natural inducible nitric oxide synthase (iNOS) inhibitors from Physalis pubescens | |
CN108948109B (zh) | 雷酚内酯苷类化合物及其应用 | |
CN110982830A (zh) | 糖基转移酶基因RyUGT3A及其编码蛋白与应用 | |
WO2019078410A1 (ko) | 진세노사이드 글리코시다제를 이용한 진세노사이드 20(s)-rg3 및 20(s)-rh2의 제조방법 | |
CN109134574B (zh) | 甾体化合物及其制备方法与应用和抗肿瘤的药物 | |
CN115109787B (zh) | 一组糖基转移酶基因及其在制备三七/人参皂苷中的应用 | |
Xiao et al. | Biocatalytic and chemical derivatization of the fungal meroditerpenoid chevalone E | |
CN109234291A (zh) | 远志齐墩果酸合酶基因PtOAS及其应用 | |
CN116144623A (zh) | 糖基转移酶突变体及其在酶法制备稀有人参皂苷中的应用 | |
CN114507646B (zh) | 细胞色素p450突变体蛋白及其应用 | |
CN110484576B (zh) | 一种提高榴菌素和榴菌素b产量的方法 | |
CN103214543A (zh) | 新山楂酸衍生物、其制备方法及其在抗肿瘤药物中的应用 | |
CN112646834A (zh) | 一种羽扇豆醇衍生物及其合成方法和应用 | |
CN109943547B (zh) | 一种茶树蔗糖合酶CsSUS587、制备方法及应用 | |
CN112300239B (zh) | 竹柏叶中甾体类化合物及其提取方法和用途 | |
CN110055232A (zh) | 二个甘草蔗糖合酶及其在合成甘草次酸糖基化衍生物中的应用 | |
CN114875095B (zh) | 一种丙氨酰美登醇及其合成方法和应用 | |
CN111205343B (zh) | 埃博霉素b的氮乙酰葡萄糖苷或半乳糖苷化合物及其酶法制备与应用 | |
CN114213497A (zh) | 筋骨草中甾体类化合物及其提取方法和用途 | |
CN109971652B (zh) | 一株藏波罗花内生真菌Onygenales X117及其发酵产物的制备方法和应用 | |
CN109776565B (zh) | 一种苦味素类化合物及其制备方法与应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |