BG60933B2 - Цитотоксичен лимфоцитен фактор на съзряване и многоклонални антитела срещу него - Google Patents

Info

Publication number

BG60933B2

BG60933B2 BG098632A BG9863294A BG60933B2 BG 60933 B2 BG60933 B2 BG 60933B2 BG 098632 A BG098632 A BG 098632A BG 9863294 A BG9863294 A BG 9863294A BG 60933 B2 BG60933 B2 BG 60933B2

Authority

BG

Bulgaria

Prior art keywords

clmf

protein

sir

leu

cells

Prior art date

1989-12-22

Links

• Espacenet
• Global Dossier
• Discuss

• 230000000527 lymphocytic effect Effects 0.000 title 1
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 218
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 209
• 210000004027 cell Anatomy 0.000 claims abstract description 153
• 238000000034 method Methods 0.000 claims abstract description 79
• 102000013462 Interleukin-12 Human genes 0.000 claims abstract description 42
• 108010065805 Interleukin-12 Proteins 0.000 claims abstract description 42
• 239000013598 vector Substances 0.000 claims abstract description 35
• 210000003810 lymphokine-activated killer cell Anatomy 0.000 claims abstract description 29
• 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 21
• 108091033319 polynucleotide Proteins 0.000 claims abstract description 19
• 102000040430 polynucleotide Human genes 0.000 claims abstract description 19
• 239000002157 polynucleotide Substances 0.000 claims abstract description 19
• 230000004936 stimulating effect Effects 0.000 claims abstract description 16
• 244000005700 microbiome Species 0.000 claims abstract description 13
• 210000000822 natural killer cell Anatomy 0.000 claims abstract description 10
• 230000008569 process Effects 0.000 claims abstract description 6
• 102000000588 Interleukin-2 Human genes 0.000 claims description 64
• 108010002350 Interleukin-2 Proteins 0.000 claims description 64
• 150000001413 amino acids Chemical group 0.000 claims description 61
• 230000000694 effects Effects 0.000 claims description 61
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 54
• 230000027455 binding Effects 0.000 claims description 39
• 239000012634 fragment Substances 0.000 claims description 39
• 239000000499 gel Substances 0.000 claims description 33
• 239000006228 supernatant Substances 0.000 claims description 33
• 239000000203 mixture Substances 0.000 claims description 32
• 238000002360 preparation method Methods 0.000 claims description 29
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
• 239000012530 fluid Substances 0.000 claims description 16
• 239000002773 nucleotide Substances 0.000 claims description 15
• 125000003729 nucleotide group Chemical group 0.000 claims description 15
• 229920000936 Agarose Polymers 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 13
• 239000001963 growth medium Substances 0.000 claims description 10
• 238000004128 high performance liquid chromatography Methods 0.000 claims description 10
• 238000012360 testing method Methods 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 230000014616 translation Effects 0.000 claims description 8
• 230000000259 anti-tumor effect Effects 0.000 claims description 7
• 239000002671 adjuvant Substances 0.000 claims description 6
• 239000011543 agarose gel Substances 0.000 claims description 6
• 239000011159 matrix material Substances 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• -1 sulfopropyl cation exchange resin Chemical compound 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 5
• 239000002246 antineoplastic agent Substances 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 3
• 238000002955 isolation Methods 0.000 claims description 3
• 239000007788 liquid Substances 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 238000007796 conventional method Methods 0.000 claims description 2
• 238000012258 culturing Methods 0.000 claims description 2
• 230000028993 immune response Effects 0.000 claims description 2
• 238000001243 protein synthesis Methods 0.000 claims description 2
• 230000000638 stimulation Effects 0.000 claims description 2
• 108010093581 aspartyl-proline Proteins 0.000 claims 3
• 238000012799 strong cation exchange Methods 0.000 claims 3
• AEZCCDMZZJOGII-DCAQKATOSA-N Asn-Met-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O AEZCCDMZZJOGII-DCAQKATOSA-N 0.000 claims 2
• KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 claims 2
• ALGGDNMLQNFVIZ-SRVKXCTJSA-N Lys-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N ALGGDNMLQNFVIZ-SRVKXCTJSA-N 0.000 claims 2
• 239000003085 diluting agent Substances 0.000 claims 2
• 108010063718 gamma-glutamylaspartic acid Proteins 0.000 claims 2
• 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 claims 2
• 108010057821 leucylproline Proteins 0.000 claims 2
• JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 claims 1
• VIGKUFXFTPWYER-BIIVOSGPSA-N Ala-Cys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N VIGKUFXFTPWYER-BIIVOSGPSA-N 0.000 claims 1
• NWVVKQZOVSTDBQ-CIUDSAMLSA-N Ala-Glu-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NWVVKQZOVSTDBQ-CIUDSAMLSA-N 0.000 claims 1
• WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 claims 1
• HHRAXZAYZFFRAM-CIUDSAMLSA-N Ala-Leu-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O HHRAXZAYZFFRAM-CIUDSAMLSA-N 0.000 claims 1
• NOGFDULFCFXBHB-CIUDSAMLSA-N Ala-Leu-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)O)N NOGFDULFCFXBHB-CIUDSAMLSA-N 0.000 claims 1
• AJBVYEYZVYPFCF-CIUDSAMLSA-N Ala-Lys-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O AJBVYEYZVYPFCF-CIUDSAMLSA-N 0.000 claims 1
• PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 claims 1
• IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 claims 1
• BUQICHWNXBIBOG-LMVFSUKVSA-N Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)N BUQICHWNXBIBOG-LMVFSUKVSA-N 0.000 claims 1
• QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 claims 1
• BVBKBQRPOJFCQM-DCAQKATOSA-N Arg-Asn-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BVBKBQRPOJFCQM-DCAQKATOSA-N 0.000 claims 1
• GDVDRMUYICMNFJ-CIUDSAMLSA-N Arg-Cys-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O GDVDRMUYICMNFJ-CIUDSAMLSA-N 0.000 claims 1
• NXDXECQFKHXHAM-HJGDQZAQSA-N Arg-Glu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NXDXECQFKHXHAM-HJGDQZAQSA-N 0.000 claims 1
• XUUXCWCKKCZEAW-YFKPBYRVSA-N Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N XUUXCWCKKCZEAW-YFKPBYRVSA-N 0.000 claims 1
• RIQBRKVTFBWEDY-RHYQMDGZSA-N Arg-Lys-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RIQBRKVTFBWEDY-RHYQMDGZSA-N 0.000 claims 1
• GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 claims 1
• FBODFHMLALOPHP-GUBZILKMSA-N Asn-Lys-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O FBODFHMLALOPHP-GUBZILKMSA-N 0.000 claims 1
• XEGZSHSPQNDNRH-JRQIVUDYSA-N Asn-Tyr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XEGZSHSPQNDNRH-JRQIVUDYSA-N 0.000 claims 1
• DVUFTQLHHHJEMK-IMJSIDKUSA-N Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O DVUFTQLHHHJEMK-IMJSIDKUSA-N 0.000 claims 1
• HPNDBHLITCHRSO-WHFBIAKZSA-N Asp-Ala-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)NCC(O)=O HPNDBHLITCHRSO-WHFBIAKZSA-N 0.000 claims 1
• XPGVTUBABLRGHY-BIIVOSGPSA-N Asp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N XPGVTUBABLRGHY-BIIVOSGPSA-N 0.000 claims 1
• PSZNHSNIGMJYOZ-WDSKDSINSA-N Asp-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PSZNHSNIGMJYOZ-WDSKDSINSA-N 0.000 claims 1
• ILJQISGMGXRZQQ-IHRRRGAJSA-N Asp-Arg-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ILJQISGMGXRZQQ-IHRRRGAJSA-N 0.000 claims 1
• PDECQIHABNQRHN-GUBZILKMSA-N Asp-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O PDECQIHABNQRHN-GUBZILKMSA-N 0.000 claims 1
• CRNKLABLTICXDV-GUBZILKMSA-N Asp-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N CRNKLABLTICXDV-GUBZILKMSA-N 0.000 claims 1
• UKGGPJNBONZZCM-WDSKDSINSA-N Asp-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O UKGGPJNBONZZCM-WDSKDSINSA-N 0.000 claims 1
• HICVMZCGVFKTPM-BQBZGAKWSA-N Asp-Pro-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HICVMZCGVFKTPM-BQBZGAKWSA-N 0.000 claims 1
• PDIYGFYAMZZFCW-JIOCBJNQSA-N Asp-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N)O PDIYGFYAMZZFCW-JIOCBJNQSA-N 0.000 claims 1
• NLCZGISONIGRQP-DCAQKATOSA-N Cys-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N NLCZGISONIGRQP-DCAQKATOSA-N 0.000 claims 1
• KXUKWRVYDYIPSQ-CIUDSAMLSA-N Cys-Leu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O KXUKWRVYDYIPSQ-CIUDSAMLSA-N 0.000 claims 1
• SSNJZBGOMNLSLA-CIUDSAMLSA-N Cys-Leu-Asn Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O SSNJZBGOMNLSLA-CIUDSAMLSA-N 0.000 claims 1
• DIHCYBRLTVEPBW-SRVKXCTJSA-N Cys-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CS)N DIHCYBRLTVEPBW-SRVKXCTJSA-N 0.000 claims 1
• UTKICHUQEQBDGC-ACZMJKKPSA-N Glu-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UTKICHUQEQBDGC-ACZMJKKPSA-N 0.000 claims 1
• FYYSIASRLDJUNP-WHFBIAKZSA-N Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FYYSIASRLDJUNP-WHFBIAKZSA-N 0.000 claims 1
• PABVKUJVLNMOJP-WHFBIAKZSA-N Glu-Cys Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(O)=O PABVKUJVLNMOJP-WHFBIAKZSA-N 0.000 claims 1
• KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 claims 1
• NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-FXQIFTODSA-N 0.000 claims 1
• PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 claims 1
• NJCALAAIGREHDR-WDCWCFNPSA-N Glu-Leu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NJCALAAIGREHDR-WDCWCFNPSA-N 0.000 claims 1
• YRMZCZIRHYCNHX-RYUDHWBXSA-N Glu-Phe-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O YRMZCZIRHYCNHX-RYUDHWBXSA-N 0.000 claims 1
• ZIYGTCDTJJCDDP-JYJNAYRXSA-N Glu-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZIYGTCDTJJCDDP-JYJNAYRXSA-N 0.000 claims 1
• JSIQVRIXMINMTA-ZDLURKLDSA-N Glu-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O JSIQVRIXMINMTA-ZDLURKLDSA-N 0.000 claims 1
• KRRMJKMGWWXWDW-STQMWFEESA-N Gly-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KRRMJKMGWWXWDW-STQMWFEESA-N 0.000 claims 1
• NTOWAXLMQFKJPT-YUMQZZPRSA-N Gly-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CN NTOWAXLMQFKJPT-YUMQZZPRSA-N 0.000 claims 1
• IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 claims 1
• FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 claims 1
• XKIYNCLILDLGRS-QWRGUYRKSA-N His-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 XKIYNCLILDLGRS-QWRGUYRKSA-N 0.000 claims 1
• UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 claims 1
• SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 claims 1
• WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 claims 1
• LESXFEZIFXFIQR-LURJTMIESA-N Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(O)=O LESXFEZIFXFIQR-LURJTMIESA-N 0.000 claims 1
• WXUOJXIGOPMDJM-SRVKXCTJSA-N Leu-Lys-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O WXUOJXIGOPMDJM-SRVKXCTJSA-N 0.000 claims 1
• RZXLZBIUTDQHJQ-SRVKXCTJSA-N Leu-Lys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O RZXLZBIUTDQHJQ-SRVKXCTJSA-N 0.000 claims 1
• VVQJGYPTIYOFBR-IHRRRGAJSA-N Leu-Lys-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)O)N VVQJGYPTIYOFBR-IHRRRGAJSA-N 0.000 claims 1
• RTIRBWJPYJYTLO-MELADBBJSA-N Leu-Lys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N RTIRBWJPYJYTLO-MELADBBJSA-N 0.000 claims 1
• WXZOHBVPVKABQN-DCAQKATOSA-N Leu-Met-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)O)N WXZOHBVPVKABQN-DCAQKATOSA-N 0.000 claims 1
• VTJUNIYRYIAIHF-IUCAKERBSA-N Leu-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O VTJUNIYRYIAIHF-IUCAKERBSA-N 0.000 claims 1
• KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 claims 1
• LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 claims 1
• ODRREERHVHMIPT-OEAJRASXSA-N Leu-Thr-Phe 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)CC1=CC=CC=C1 ODRREERHVHMIPT-OEAJRASXSA-N 0.000 claims 1
• RVOMPSJXSRPFJT-DCAQKATOSA-N Lys-Ala-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVOMPSJXSRPFJT-DCAQKATOSA-N 0.000 claims 1
• JGAMUXDWYSXYLM-SRVKXCTJSA-N Lys-Arg-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O JGAMUXDWYSXYLM-SRVKXCTJSA-N 0.000 claims 1
• QYOXSYXPHUHOJR-GUBZILKMSA-N Lys-Asn-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYOXSYXPHUHOJR-GUBZILKMSA-N 0.000 claims 1
• ZQCVMVCVPFYXHZ-SRVKXCTJSA-N Lys-Asn-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN ZQCVMVCVPFYXHZ-SRVKXCTJSA-N 0.000 claims 1
• PAMDBWYMLWOELY-SDDRHHMPSA-N Lys-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O PAMDBWYMLWOELY-SDDRHHMPSA-N 0.000 claims 1
• PINHPJWGVBKQII-SRVKXCTJSA-N Lys-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N PINHPJWGVBKQII-SRVKXCTJSA-N 0.000 claims 1
• UQRZFMQQXXJTTF-AVGNSLFASA-N Lys-Lys-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O UQRZFMQQXXJTTF-AVGNSLFASA-N 0.000 claims 1
• WGILOYIKJVQUPT-DCAQKATOSA-N Lys-Pro-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WGILOYIKJVQUPT-DCAQKATOSA-N 0.000 claims 1
• XYLSGAWRCZECIQ-JYJNAYRXSA-N Lys-Tyr-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 XYLSGAWRCZECIQ-JYJNAYRXSA-N 0.000 claims 1
• JMEWFDUAFKVAAT-WDSKDSINSA-N Met-Asn Chemical compound CSCC[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CC(N)=O JMEWFDUAFKVAAT-WDSKDSINSA-N 0.000 claims 1
• NTYQUVLERIHPMU-HRCADAONSA-N Met-Phe-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N NTYQUVLERIHPMU-HRCADAONSA-N 0.000 claims 1
• PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 claims 1
• XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 claims 1
• 108010002311 N-glycylglutamic acid Proteins 0.000 claims 1
• YKUGPVXSDOOANW-KKUMJFAQSA-N Phe-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YKUGPVXSDOOANW-KKUMJFAQSA-N 0.000 claims 1
• LYCOGHUNJCETDK-JYJNAYRXSA-N Phe-Met-Met Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N LYCOGHUNJCETDK-JYJNAYRXSA-N 0.000 claims 1
• GKZIWHRNKRBEOH-HOTGVXAUSA-N Phe-Phe Chemical compound C([C@H]([NH3+])C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)C1=CC=CC=C1 GKZIWHRNKRBEOH-HOTGVXAUSA-N 0.000 claims 1
• RAGOJJCBGXARPO-XVSYOHENSA-N Phe-Thr-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 RAGOJJCBGXARPO-XVSYOHENSA-N 0.000 claims 1
• SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 claims 1
• HXOLCSYHGRNXJJ-IHRRRGAJSA-N Pro-Asp-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HXOLCSYHGRNXJJ-IHRRRGAJSA-N 0.000 claims 1
• SFECXGVELZFBFJ-VEVYYDQMSA-N Pro-Asp-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SFECXGVELZFBFJ-VEVYYDQMSA-N 0.000 claims 1
• HXNYBZQLBWIADP-WDSKDSINSA-N Pro-Cys Chemical compound OC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1 HXNYBZQLBWIADP-WDSKDSINSA-N 0.000 claims 1
• JUJCUYWRJMFJJF-AVGNSLFASA-N Pro-Lys-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 JUJCUYWRJMFJJF-AVGNSLFASA-N 0.000 claims 1
• PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 claims 1
• 108010054530 RGDN peptide Proteins 0.000 claims 1
• TZKPNGDGUVREEB-FOHZUACHSA-N Thr-Asn-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O TZKPNGDGUVREEB-FOHZUACHSA-N 0.000 claims 1
• IOWJRKAVLALBQB-IWGUZYHVSA-N Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O IOWJRKAVLALBQB-IWGUZYHVSA-N 0.000 claims 1
• NLSNVZAREYQMGR-HJGDQZAQSA-N Thr-Asp-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NLSNVZAREYQMGR-HJGDQZAQSA-N 0.000 claims 1
• LYGKYFKSZTUXGZ-ZDLURKLDSA-N Thr-Cys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)NCC(O)=O LYGKYFKSZTUXGZ-ZDLURKLDSA-N 0.000 claims 1
• VLIUBAATANYCOY-GBALPHGKSA-N Thr-Cys-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VLIUBAATANYCOY-GBALPHGKSA-N 0.000 claims 1
• VTVVYQOXJCZVEB-WDCWCFNPSA-N Thr-Leu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VTVVYQOXJCZVEB-WDCWCFNPSA-N 0.000 claims 1
• ZSPQUTWLWGWTPS-HJGDQZAQSA-N Thr-Lys-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZSPQUTWLWGWTPS-HJGDQZAQSA-N 0.000 claims 1
• WNQJTLATMXYSEL-OEAJRASXSA-N Thr-Phe-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WNQJTLATMXYSEL-OEAJRASXSA-N 0.000 claims 1
• JAJOFWABAUKAEJ-QTKMDUPCSA-N Thr-Pro-His Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O JAJOFWABAUKAEJ-QTKMDUPCSA-N 0.000 claims 1
• ZEJBJDHSQPOVJV-UAXMHLISSA-N Thr-Trp-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZEJBJDHSQPOVJV-UAXMHLISSA-N 0.000 claims 1
• OHGNSVACHBZKSS-KWQFWETISA-N Trp-Ala Chemical compound C1=CC=C2C(C[C@H]([NH3+])C(=O)N[C@@H](C)C([O-])=O)=CNC2=C1 OHGNSVACHBZKSS-KWQFWETISA-N 0.000 claims 1
• YXONONCLMLHWJX-SZMVWBNQSA-N Trp-Glu-Leu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O)=CNC2=C1 YXONONCLMLHWJX-SZMVWBNQSA-N 0.000 claims 1
• HXNVJPQADLRHGR-JBACZVJFSA-N Trp-Glu-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)N HXNVJPQADLRHGR-JBACZVJFSA-N 0.000 claims 1
• UKWSFUSPGPBJGU-VFAJRCTISA-N Trp-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O UKWSFUSPGPBJGU-VFAJRCTISA-N 0.000 claims 1
• ICPRIGUXAFULPH-ILWGZMRPSA-N Trp-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N)C(=O)O ICPRIGUXAFULPH-ILWGZMRPSA-N 0.000 claims 1
• HKYTWJOWZTWBQB-AVGNSLFASA-N Tyr-Glu-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HKYTWJOWZTWBQB-AVGNSLFASA-N 0.000 claims 1
• NJLQMKZSXYQRTO-FHWLQOOXSA-N Tyr-Glu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NJLQMKZSXYQRTO-FHWLQOOXSA-N 0.000 claims 1
• MVFQLSPDMMFCMW-KKUMJFAQSA-N Tyr-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O MVFQLSPDMMFCMW-KKUMJFAQSA-N 0.000 claims 1
• SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 claims 1
• CGWAPUBOXJWXMS-HOTGVXAUSA-N Tyr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 CGWAPUBOXJWXMS-HOTGVXAUSA-N 0.000 claims 1
• QFHRUCJIRVILCK-YJRXYDGGSA-N Tyr-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O QFHRUCJIRVILCK-YJRXYDGGSA-N 0.000 claims 1
• 108010069020 alanyl-prolyl-glycine Proteins 0.000 claims 1
• KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 claims 1
• 238000005349 anion exchange Methods 0.000 claims 1
• 150000001450 anions Chemical class 0.000 claims 1
• 108010092854 aspartyllysine Proteins 0.000 claims 1
• 238000006664 bond formation reaction Methods 0.000 claims 1
• 239000003729 cation exchange resin Substances 0.000 claims 1
• 210000004748 cultured cell Anatomy 0.000 claims 1
• FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 claims 1
• 125000002228 disulfide group Chemical group 0.000 claims 1
• 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 claims 1
• 108010055341 glutamyl-glutamic acid Proteins 0.000 claims 1
• 108010049041 glutamylalanine Proteins 0.000 claims 1
• VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 claims 1
• 108010050848 glycylleucine Proteins 0.000 claims 1
• 108010015792 glycyllysine Proteins 0.000 claims 1
• 108010040030 histidinoalanine Proteins 0.000 claims 1
• 108010028295 histidylhistidine Proteins 0.000 claims 1
• 238000002386 leaching Methods 0.000 claims 1
• 108010034529 leucyl-lysine Proteins 0.000 claims 1
• 108010090333 leucyl-lysyl-proline Proteins 0.000 claims 1
• 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 claims 1
• 108010000761 leucylarginine Proteins 0.000 claims 1
• 238000004811 liquid chromatography Methods 0.000 claims 1
• 230000014759 maintenance of location Effects 0.000 claims 1
• 108010073025 phenylalanylphenylalanine Proteins 0.000 claims 1
• 108010070643 prolylglutamic acid Proteins 0.000 claims 1
• 241000894007 species Species 0.000 claims 1
• 230000001131 transforming effect Effects 0.000 claims 1
• 108010045269 tryptophyltryptophan Proteins 0.000 claims 1
• 108010020532 tyrosyl-proline Proteins 0.000 claims 1
• 108010003137 tyrosyltyrosine Proteins 0.000 claims 1
• 241000282414 Homo sapiens Species 0.000 abstract description 50
• 102000004127 Cytokines Human genes 0.000 abstract description 35
• 108090000695 Cytokines Proteins 0.000 abstract description 35
• 230000001461 cytolytic effect Effects 0.000 abstract description 10
• 238000010367 cloning Methods 0.000 abstract description 7
• 230000012010 growth Effects 0.000 abstract description 4
• 235000018102 proteins Nutrition 0.000 description 139
• 210000002966 serum Anatomy 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 229940024606 amino acid Drugs 0.000 description 33
• 235000001014 amino acid Nutrition 0.000 description 33
• 238000003556 assay Methods 0.000 description 33
• 239000002299 complementary DNA Substances 0.000 description 32
• 241000700159 Rattus Species 0.000 description 28
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
• 239000010414 supernatant solution Substances 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
• 108020004414 DNA Proteins 0.000 description 22
• 239000000872 buffer Substances 0.000 description 22
• 210000004408 hybridoma Anatomy 0.000 description 22
• 239000000523 sample Substances 0.000 description 22
• 210000004698 lymphocyte Anatomy 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 18
• 239000012528 membrane Substances 0.000 description 18
• 239000000243 solution Substances 0.000 description 17
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 16
• 230000006698 induction Effects 0.000 description 16
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
• 150000003839 salts Chemical class 0.000 description 16
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 16
• 238000010828 elution Methods 0.000 description 15
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 15
• 102000005962 receptors Human genes 0.000 description 15
• 108020003175 receptors Proteins 0.000 description 15
• 230000002829 reductive effect Effects 0.000 description 15
• 239000011780 sodium chloride Substances 0.000 description 15
• 108091093088 Amplicon Proteins 0.000 description 14
• 101000852992 Homo sapiens Interleukin-12 subunit beta Proteins 0.000 description 14
• 108091028043 Nucleic acid sequence Proteins 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 238000002474 experimental method Methods 0.000 description 14
• 239000000833 heterodimer Substances 0.000 description 14
• 102000050932 human IL12B Human genes 0.000 description 14
• 230000002401 inhibitory effect Effects 0.000 description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
• 238000000926 separation method Methods 0.000 description 14
• 238000001262 western blot Methods 0.000 description 14
• 238000005119 centrifugation Methods 0.000 description 13
• 238000010790 dilution Methods 0.000 description 13
• 239000012895 dilution Substances 0.000 description 13
• 201000001441 melanoma Diseases 0.000 description 13
• 230000035755 proliferation Effects 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 11
• 238000003018 immunoassay Methods 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 238000006386 neutralization reaction Methods 0.000 description 11
• 239000013612 plasmid Substances 0.000 description 11
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 11
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 11
• 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 10
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 10
• 239000007983 Tris buffer Substances 0.000 description 10
• 108090000631 Trypsin Proteins 0.000 description 10
• 102000004142 Trypsin Human genes 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000012228 culture supernatant Substances 0.000 description 10
• 239000002953 phosphate buffered saline Substances 0.000 description 10
• 230000004044 response Effects 0.000 description 10
• 239000003104 tissue culture media Substances 0.000 description 10
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 10
• 239000012588 trypsin Substances 0.000 description 10
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
• 241000283707 Capra Species 0.000 description 9
• 206010028980 Neoplasm Diseases 0.000 description 9
• 241000283973 Oryctolagus cuniculus Species 0.000 description 9
• 231100000433 cytotoxic Toxicity 0.000 description 9
• 230000001472 cytotoxic effect Effects 0.000 description 9
• 238000011534 incubation Methods 0.000 description 9
• 230000002441 reversible effect Effects 0.000 description 9
• 238000010561 standard procedure Methods 0.000 description 9
• 238000012546 transfer Methods 0.000 description 9
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 239000000020 Nitrocellulose Substances 0.000 description 8
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 8
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
• 210000003969 blast cell Anatomy 0.000 description 8
• 229940098773 bovine serum albumin Drugs 0.000 description 8
• 239000006285 cell suspension Substances 0.000 description 8
• 230000009089 cytolysis Effects 0.000 description 8
• 239000013604 expression vector Substances 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 230000002101 lytic effect Effects 0.000 description 8
• 229920001220 nitrocellulos Polymers 0.000 description 8
• 230000036961 partial effect Effects 0.000 description 8
• 238000004007 reversed phase HPLC Methods 0.000 description 8
• 238000012882 sequential analysis Methods 0.000 description 8
• 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 8
• 229940104230 thymidine Drugs 0.000 description 8
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 7
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 7
• 108091034117 Oligonucleotide Proteins 0.000 description 7
• 238000001042 affinity chromatography Methods 0.000 description 7
• 239000011324 bead Substances 0.000 description 7
• 239000004305 biphenyl Substances 0.000 description 7
• 235000010290 biphenyl Nutrition 0.000 description 7
• 125000006267 biphenyl group Chemical group 0.000 description 7
• 238000004113 cell culture Methods 0.000 description 7
• 230000001413 cellular effect Effects 0.000 description 7
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 7
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
• 235000018417 cysteine Nutrition 0.000 description 7
• 231100000673 dose–response relationship Toxicity 0.000 description 7
• 238000001114 immunoprecipitation Methods 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 7
• 230000003472 neutralizing effect Effects 0.000 description 7
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 238000012216 screening Methods 0.000 description 7
• 101710134681 40 kDa protein Proteins 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 208000032843 Hemorrhage Diseases 0.000 description 6
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 6
• 108010033276 Peptide Fragments Proteins 0.000 description 6
• 102000007079 Peptide Fragments Human genes 0.000 description 6
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 6
• 239000012980 RPMI-1640 medium Substances 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 239000012636 effector Substances 0.000 description 6
• 239000012133 immunoprecipitate Substances 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 229920002401 polyacrylamide Polymers 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000002243 precursor Substances 0.000 description 6
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
• 230000009257 reactivity Effects 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 241000283690 Bos taurus Species 0.000 description 5
• 108020004635 Complementary DNA Proteins 0.000 description 5
• 241000588724 Escherichia coli Species 0.000 description 5
• 239000004471 Glycine Substances 0.000 description 5
• 229930182816 L-glutamine Natural products 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
• 108010076504 Protein Sorting Signals Proteins 0.000 description 5
• 230000000740 bleeding effect Effects 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 229930195712 glutamate Natural products 0.000 description 5
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
• 238000009396 hybridization Methods 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 230000035800 maturation Effects 0.000 description 5
• 108020004999 messenger RNA Proteins 0.000 description 5
• 229930182817 methionine Natural products 0.000 description 5
• 229920001184 polypeptide Polymers 0.000 description 5
• 238000001556 precipitation Methods 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 238000001525 receptor binding assay Methods 0.000 description 5
• 238000011160 research Methods 0.000 description 5
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
• 239000004475 Arginine Substances 0.000 description 4
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
• 101710172503 Chemokine-binding protein Proteins 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 239000012981 Hank's balanced salt solution Substances 0.000 description 4
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• 239000004472 Lysine Substances 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 101710138270 PspA protein Proteins 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
• 229960003121 arginine Drugs 0.000 description 4
• 229960001230 asparagine Drugs 0.000 description 4
• 235000009582 asparagine Nutrition 0.000 description 4
• 229940009098 aspartate Drugs 0.000 description 4
• 239000011575 calcium Substances 0.000 description 4
• 239000004202 carbamide Substances 0.000 description 4
• 238000012512 characterization method Methods 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 238000003776 cleavage reaction Methods 0.000 description 4
• 238000005520 cutting process Methods 0.000 description 4
• 238000004925 denaturation Methods 0.000 description 4
• 230000036425 denaturation Effects 0.000 description 4
• 230000029087 digestion Effects 0.000 description 4
• 230000004927 fusion Effects 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 239000001307 helium Substances 0.000 description 4
• 229910052734 helium Inorganic materials 0.000 description 4
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 238000010348 incorporation Methods 0.000 description 4
• 230000000977 initiatory effect Effects 0.000 description 4
• 238000003780 insertion Methods 0.000 description 4
• 230000037431 insertion Effects 0.000 description 4
• 229960000310 isoleucine Drugs 0.000 description 4
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
• 238000002493 microarray Methods 0.000 description 4
• 239000013014 purified material Substances 0.000 description 4
• 239000011347 resin Substances 0.000 description 4
• 229920005989 resin Polymers 0.000 description 4
• 230000007017 scission Effects 0.000 description 4
• 229910052709 silver Inorganic materials 0.000 description 4
• 239000004332 silver Substances 0.000 description 4
• 210000004989 spleen cell Anatomy 0.000 description 4
• 229960005322 streptomycin Drugs 0.000 description 4
• 230000002195 synergetic effect Effects 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 238000013519 translation Methods 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• QTQGHKVYLQBJLO-UHFFFAOYSA-N 4-methylbenzenesulfonate;(4-methyl-1-oxo-1-phenylmethoxypentan-2-yl)azanium Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC(C)CC(N)C(=O)OCC1=CC=CC=C1 QTQGHKVYLQBJLO-UHFFFAOYSA-N 0.000 description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
• 108020004705 Codon Proteins 0.000 description 3
• 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 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 229920001917 Ficoll Polymers 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
• 229930182555 Penicillin Natural products 0.000 description 3
• 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 3
• 108020004511 Recombinant DNA Proteins 0.000 description 3
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
• 229920002684 Sepharose Polymers 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
• 239000004473 Threonine Substances 0.000 description 3
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 235000004279 alanine Nutrition 0.000 description 3
• 210000004102 animal cell Anatomy 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 239000013060 biological fluid Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 3
• 239000012531 culture fluid Substances 0.000 description 3
• 238000010586 diagram Methods 0.000 description 3
• 238000001962 electrophoresis Methods 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 3
• 229960004198 guanidine Drugs 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 229960001401 hydrocortisone sodium succinate Drugs 0.000 description 3
• 230000003053 immunization Effects 0.000 description 3
• 238000002649 immunization Methods 0.000 description 3
• 238000006192 iodination reaction Methods 0.000 description 3
• 238000004255 ion exchange chromatography Methods 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 229940049954 penicillin Drugs 0.000 description 3
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
• 239000008363 phosphate buffer Substances 0.000 description 3
• 230000017854 proteolysis Effects 0.000 description 3
• 108091008146 restriction endonucleases Proteins 0.000 description 3
• 238000012163 sequencing technique Methods 0.000 description 3
• 238000013207 serial dilution Methods 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 108010001857 Cell Surface Receptors Proteins 0.000 description 2
• 108091033380 Coding strand Proteins 0.000 description 2
• 241001559589 Cullen Species 0.000 description 2
• PJWWRFATQTVXHA-UHFFFAOYSA-N Cyclohexylaminopropanesulfonic acid Chemical compound OS(=O)(=O)CCCNC1CCCCC1 PJWWRFATQTVXHA-UHFFFAOYSA-N 0.000 description 2
• 102000053602 DNA Human genes 0.000 description 2
• 108010017826 DNA Polymerase I Proteins 0.000 description 2
• 102000004594 DNA Polymerase I Human genes 0.000 description 2
• 241000701959 Escherichia virus Lambda Species 0.000 description 2
• 229930182566 Gentamicin Natural products 0.000 description 2
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• 241001622557 Hesperia Species 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 206010062016 Immunosuppression Diseases 0.000 description 2
• YEJSPQZHMWGIGP-YFKPBYRVSA-N L-glutamic acid, dimethyl ester Chemical compound COC(=O)CC[C@H](N)C(=O)OC YEJSPQZHMWGIGP-YFKPBYRVSA-N 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 108700026244 Open Reading Frames Proteins 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 239000012083 RIPA buffer Substances 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 230000006052 T cell proliferation Effects 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 239000002250 absorbent Substances 0.000 description 2
• 230000002745 absorbent Effects 0.000 description 2
• QPMSXSBEVQLBIL-CZRHPSIPSA-N ac1mix0p Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1.O([C@H]1[C@]2(OC)C=CC34C[C@@H]2[C@](C)(O)CCC)C2=C5[C@]41CCN(C)[C@@H]3CC5=CC=C2O QPMSXSBEVQLBIL-CZRHPSIPSA-N 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000000853 adhesive Substances 0.000 description 2
• 230000001070 adhesive effect Effects 0.000 description 2
• 230000000735 allogeneic effect Effects 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 238000000376 autoradiography Methods 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 239000003710 calcium ionophore Substances 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 230000007910 cell fusion Effects 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 230000036755 cellular response Effects 0.000 description 2
• 230000002759 chromosomal effect Effects 0.000 description 2
• 239000012141 concentrate Substances 0.000 description 2
• 239000003636 conditioned culture medium Substances 0.000 description 2
• 239000000356 contaminant Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 238000011266 cytolytic assay Methods 0.000 description 2
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
• 238000000354 decomposition reaction Methods 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 239000008367 deionised water Substances 0.000 description 2
• 229910021641 deionized water Inorganic materials 0.000 description 2
• 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 2
• 239000012153 distilled water Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 239000013613 expression plasmid Substances 0.000 description 2
• 229960002518 gentamicin Drugs 0.000 description 2
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 230000001506 immunosuppresive effect Effects 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 230000026045 iodination Effects 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 102000006240 membrane receptors Human genes 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 238000010369 molecular cloning Methods 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 210000005259 peripheral blood Anatomy 0.000 description 2
• 239000011886 peripheral blood Substances 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• 108010086652 phytohemagglutinin-P Proteins 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 230000002797 proteolythic effect Effects 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 238000002741 site-directed mutagenesis Methods 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 210000001541 thymus gland Anatomy 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 238000001890 transfection Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• 239000011534 wash buffer Substances 0.000 description 2
• GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
• PQMRRAQXKWFYQN-UHFFFAOYSA-N 1-phenyl-2-sulfanylideneimidazolidin-4-one Chemical compound S=C1NC(=O)CN1C1=CC=CC=C1 PQMRRAQXKWFYQN-UHFFFAOYSA-N 0.000 description 1
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
• HTCSFFGLRQDZDE-UHFFFAOYSA-N 2-azaniumyl-2-phenylpropanoate Chemical compound OC(=O)C(N)(C)C1=CC=CC=C1 HTCSFFGLRQDZDE-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
• QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
• GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
• LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 1
• HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• GGZZISOUXJHYOY-UHFFFAOYSA-N 8-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(N)=CC=CC2=C1O GGZZISOUXJHYOY-UHFFFAOYSA-N 0.000 description 1
• UBDHSURDYAETAL-UHFFFAOYSA-N 8-aminonaphthalene-1,3,6-trisulfonic acid Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(N)=CC(S(O)(=O)=O)=CC2=C1 UBDHSURDYAETAL-UHFFFAOYSA-N 0.000 description 1
• 102000013563 Acid Phosphatase Human genes 0.000 description 1
• 108010051457 Acid Phosphatase Proteins 0.000 description 1
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 101800001415 Bri23 peptide Proteins 0.000 description 1
• 101800000655 C-terminal peptide Proteins 0.000 description 1
• 102400000107 C-terminal peptide Human genes 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 101800005309 Carboxy-terminal peptide Proteins 0.000 description 1
• 241000282552 Chlorocebus aethiops Species 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 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
• 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
• 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 1
• 241000282412 Homo Species 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
• 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 102000008072 Lymphokines Human genes 0.000 description 1
• 108010074338 Lymphokines Proteins 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 241000721701 Lynx Species 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102000013967 Monokines Human genes 0.000 description 1
• 108010050619 Monokines Proteins 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 101800000135 N-terminal protein Proteins 0.000 description 1
• 230000006051 NK cell activation Effects 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 229920002274 Nalgene Polymers 0.000 description 1
• 241001460678 Napo <wasp> Species 0.000 description 1
• 238000000636 Northern blotting Methods 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 101800001452 P1 proteinase Proteins 0.000 description 1
• 238000013494 PH determination Methods 0.000 description 1
• 101150012394 PHO5 gene Proteins 0.000 description 1
• 241000237988 Patellidae Species 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
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 238000002123 RNA extraction Methods 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 241001187220 Rouya Species 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 241000191967 Staphylococcus aureus Species 0.000 description 1
• 101000829189 Staphylococcus aureus Glutamyl endopeptidase Proteins 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 229940126530 T cell activator Drugs 0.000 description 1
• 102000000479 TCF Transcription Factors Human genes 0.000 description 1
• 108010016283 TCF Transcription Factors Proteins 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• VSYMNDBTCKIDLT-UHFFFAOYSA-N [2-(carbamoyloxymethyl)-2-ethylbutyl] carbamate Chemical compound NC(=O)OCC(CC)(CC)COC(N)=O VSYMNDBTCKIDLT-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
• 150000003862 amino acid derivatives Chemical class 0.000 description 1
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 230000003698 anagen phase Effects 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 229960003589 arginine hydrochloride Drugs 0.000 description 1
• 210000003567 ascitic fluid Anatomy 0.000 description 1
• 230000003305 autocrine Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000012148 binding buffer Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 239000005388 borosilicate glass Substances 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
• HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 108091092356 cellular DNA Proteins 0.000 description 1
• 108091092328 cellular RNA Proteins 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 239000012539 chromatography resin Substances 0.000 description 1
• 238000002983 circular dichroism Methods 0.000 description 1
• 210000000078 claw Anatomy 0.000 description 1
• 230000003749 cleanliness Effects 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 230000000515 cyanogenic effect Effects 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 229960003964 deoxycholic acid Drugs 0.000 description 1
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
• KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
• 238000011033 desalting Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 238000002050 diffraction method Methods 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000007877 drug screening Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 210000002257 embryonic structure Anatomy 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
• 229960005542 ethidium bromide Drugs 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 210000004709 eyebrow Anatomy 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
• 230000001605 fetal effect Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000007667 floating Methods 0.000 description 1
• 238000001917 fluorescence detection Methods 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 108060003552 hemocyanin Proteins 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
• 229960000890 hydrocortisone Drugs 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 210000001822 immobilized cell Anatomy 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 238000012744 immunostaining Methods 0.000 description 1
• 230000003308 immunostimulating effect Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
• 238000001155 isoelectric focusing Methods 0.000 description 1
• 238000001948 isotopic labelling Methods 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229960003136 leucine Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007791 liquid phase Substances 0.000 description 1
• 238000005567 liquid scintillation counting Methods 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 230000008774 maternal effect Effects 0.000 description 1
• QVDXUKJJGUSGLS-LURJTMIESA-N methyl L-leucinate Chemical compound COC(=O)[C@@H](N)CC(C)C QVDXUKJJGUSGLS-LURJTMIESA-N 0.000 description 1
• 108010077055 methylated bovine serum albumin Proteins 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 229940105132 myristate Drugs 0.000 description 1
• 230000010807 negative regulation of binding Effects 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 229920002113 octoxynol Polymers 0.000 description 1
• 238000002515 oligonucleotide synthesis Methods 0.000 description 1
• 210000000287 oocyte Anatomy 0.000 description 1
• 230000003076 paracrine Effects 0.000 description 1
• 239000006201 parenteral dosage form Substances 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 229940117953 phenylisothiocyanate Drugs 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 210000004180 plasmocyte Anatomy 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
• 229940116357 potassium thiocyanate Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 238000002601 radiography Methods 0.000 description 1
• 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 229920002545 silicone oil Polymers 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• ZEYOIOAKZLALAP-UHFFFAOYSA-M sodium amidotrizoate Chemical compound [Na+].CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I ZEYOIOAKZLALAP-UHFFFAOYSA-M 0.000 description 1
• PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 238000009987 spinning Methods 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000012289 standard assay Methods 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000007723 transport mechanism Effects 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
• 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 230000002747 voluntary effect Effects 0.000 description 1