PH26508A - A method for the selective cleavage of fusion proteins - Google Patents
A method for the selective cleavage of fusion proteins Download PDFInfo
- Publication number
- PH26508A PH26508A PH39449A PH39449A PH26508A PH 26508 A PH26508 A PH 26508A PH 39449 A PH39449 A PH 39449A PH 39449 A PH39449 A PH 39449A PH 26508 A PH26508 A PH 26508A
- Authority
- PH
- Philippines
- Prior art keywords
- formula
- thr
- lys
- peptide
- denotes
- Prior art date
Links
- 238000003776 cleavage reaction Methods 0.000 title claims abstract description 18
- 230000007017 scission Effects 0.000 title claims abstract description 18
- 108020001507 fusion proteins Proteins 0.000 title claims abstract description 17
- 102000037865 fusion proteins Human genes 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims description 35
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 21
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 20
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 20
- 108010059378 Endopeptidases Proteins 0.000 claims abstract description 15
- 102000005593 Endopeptidases Human genes 0.000 claims abstract description 15
- 230000001810 trypsinlike Effects 0.000 claims abstract description 12
- 239000003392 amylase inhibitor Substances 0.000 claims abstract description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 8
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 7
- 229920001184 polypeptide Polymers 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 13
- 229940122816 Amylase inhibitor Drugs 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims 2
- 101150094949 APRT gene Proteins 0.000 claims 1
- 241001553014 Myrsine salicina Species 0.000 claims 1
- 101100285000 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-3 gene Proteins 0.000 claims 1
- 241000183024 Populus tremula Species 0.000 claims 1
- 238000002271 resection Methods 0.000 claims 1
- 102220047090 rs6152 Human genes 0.000 claims 1
- 102000004877 Insulin Human genes 0.000 abstract description 16
- 108090001061 Insulin Proteins 0.000 abstract description 16
- -1 for example Proteins 0.000 abstract description 10
- 239000004026 insulin derivative Substances 0.000 abstract description 10
- 101000976075 Homo sapiens Insulin Proteins 0.000 abstract description 8
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 abstract description 7
- 238000002425 crystallisation Methods 0.000 abstract description 6
- 238000010353 genetic engineering Methods 0.000 abstract description 4
- 239000007795 chemical reaction product Substances 0.000 abstract description 3
- 101710171801 Alpha-amylase inhibitor Proteins 0.000 abstract 1
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 25
- 235000013350 formula milk Nutrition 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 229940125396 insulin Drugs 0.000 description 11
- 239000004382 Amylase Substances 0.000 description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 102000013142 Amylases Human genes 0.000 description 6
- 108010065511 Amylases Proteins 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 235000019418 amylase Nutrition 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 150000003587 threonine derivatives Chemical class 0.000 description 5
- 108010075254 C-Peptide Proteins 0.000 description 4
- 108010005991 Pork Regular Insulin Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000252067 Megalops atlanticus Species 0.000 description 3
- 108010078762 Protein Precursors Proteins 0.000 description 3
- 102000014961 Protein Precursors Human genes 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 229940066758 endopeptidases Drugs 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 108010066381 preproinsulin Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 101500021084 Locusta migratoria 5 kDa peptide Proteins 0.000 description 2
- 108010053229 Lysyl endopeptidase Proteins 0.000 description 2
- 108010076181 Proinsulin Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- AUXMWYRZQPIXCC-KNIFDHDWSA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O AUXMWYRZQPIXCC-KNIFDHDWSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- QADCERNTBWTXFV-JSGCOSHPSA-N Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCNC(N)=N)N)C(O)=O)=CNC2=C1 QADCERNTBWTXFV-JSGCOSHPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- KWBQPGIYEZKDEG-FSPLSTOPSA-N Asn-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O KWBQPGIYEZKDEG-FSPLSTOPSA-N 0.000 description 1
- NTQDELBZOMWXRS-IWGUZYHVSA-N Asp-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O NTQDELBZOMWXRS-IWGUZYHVSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100353414 Caenorhabditis elegans pfn-2 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 235000016796 Euonymus japonicus Nutrition 0.000 description 1
- 240000006570 Euonymus japonicus Species 0.000 description 1
- SCCPDJAQCXWPTF-VKHMYHEASA-N Gly-Asp Chemical compound NCC(=O)N[C@H](C(O)=O)CC(O)=O SCCPDJAQCXWPTF-VKHMYHEASA-N 0.000 description 1
- PNMUAGGSDZXTHX-BYPYZUCNSA-N Gly-Gln Chemical compound NCC(=O)N[C@H](C(O)=O)CCC(N)=O PNMUAGGSDZXTHX-BYPYZUCNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000760663 Hololena curta Mu-agatoxin-Hc1a Proteins 0.000 description 1
- 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 1
- 102100027612 Kallikrein-11 Human genes 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 241000863031 Lysobacter Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 101710127332 Protease I Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
- 241001655322 Streptomycetales Species 0.000 description 1
- 101710137710 Thioesterase 1/protease 1/lysophospholipase L1 Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 101710152431 Trypsin-like protease Proteins 0.000 description 1
- HPYDSVWYXXKHRD-VIFPVBQESA-N Tyr-Gly Chemical compound [O-]C(=O)CNC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 HPYDSVWYXXKHRD-VIFPVBQESA-N 0.000 description 1
- ZSXJENBJGRHKIG-UWVGGRQHSA-N Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ZSXJENBJGRHKIG-UWVGGRQHSA-N 0.000 description 1
- OYOQKMOWUDVWCR-RYUDHWBXSA-N Tyr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OYOQKMOWUDVWCR-RYUDHWBXSA-N 0.000 description 1
- MUXFZBHBYYYLTH-UHFFFAOYSA-N Zaltoprofen Chemical compound O=C1CC2=CC(C(C(O)=O)C)=CC=C2SC2=CC=CC=C21 MUXFZBHBYYYLTH-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940124280 l-arginine Drugs 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000007030 peptide scission Effects 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 229940070376 protein Drugs 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- 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
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Engineering & Computer Science (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Welding Or Cutting Using Electron Beams (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Semiconductor Integrated Circuits (AREA)
- Fuses (AREA)
- Design And Manufacture Of Integrated Circuits (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3837271A DE3837271A1 (de) | 1988-11-03 | 1988-11-03 | Verfahren zur selektiven spaltung von fusionsproteinen |
Publications (1)
Publication Number | Publication Date |
---|---|
PH26508A true PH26508A (en) | 1992-08-07 |
Family
ID=6366365
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PH39449A PH26508A (en) | 1988-11-03 | 1989-11-02 | A method for the selective cleavage of fusion proteins |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0367161B1 (fi) |
JP (1) | JP2877253B2 (fi) |
KR (1) | KR900007865A (fi) |
AT (1) | ATE139538T1 (fi) |
AU (1) | AU618420B2 (fi) |
DE (2) | DE3837271A1 (fi) |
DK (1) | DK546689A (fi) |
ES (1) | ES2088883T3 (fi) |
FI (1) | FI895183A0 (fi) |
GR (1) | GR3020297T3 (fi) |
HU (1) | HUT53677A (fi) |
IL (1) | IL92179A0 (fi) |
NO (1) | NO894362L (fi) |
NZ (1) | NZ231221A (fi) |
PH (1) | PH26508A (fi) |
PT (1) | PT92176B (fi) |
ZA (1) | ZA898376B (fi) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012048856A1 (en) | 2010-10-12 | 2012-04-19 | Glucometrix Pvs Gmbh | Proinsulin with helper sequence |
WO2012098009A1 (en) | 2011-01-21 | 2012-07-26 | Glucometrix Ag | Chimeric polypeptide comprising a membrane protein and an insulin precursor |
EP2867250A2 (en) | 2012-04-04 | 2015-05-06 | GlucoMetrix AG | Proinsulin with enhanced helper sequence |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3418274A1 (de) * | 1984-05-17 | 1985-11-21 | Hoechst Ag, 6230 Frankfurt | Signalpeptid fuer die exkretion von peptiden in streptomyceten |
DK129385A (da) * | 1985-03-22 | 1986-09-23 | Novo Industri As | Peptider og fremstilling deraf |
DE3707150A1 (de) * | 1987-03-06 | 1988-09-15 | Hoechst Ag | Tendamistat-derivate |
-
1988
- 1988-11-03 DE DE3837271A patent/DE3837271A1/de not_active Withdrawn
-
1989
- 1989-10-28 ES ES89120054T patent/ES2088883T3/es not_active Expired - Lifetime
- 1989-10-28 AT AT89120054T patent/ATE139538T1/de not_active IP Right Cessation
- 1989-10-28 DE DE58909692T patent/DE58909692D1/de not_active Expired - Lifetime
- 1989-10-28 EP EP89120054A patent/EP0367161B1/de not_active Expired - Lifetime
- 1989-11-01 FI FI895183A patent/FI895183A0/fi not_active Application Discontinuation
- 1989-11-01 NZ NZ231221A patent/NZ231221A/xx unknown
- 1989-11-01 IL IL92179A patent/IL92179A0/xx unknown
- 1989-11-02 PH PH39449A patent/PH26508A/en unknown
- 1989-11-02 AU AU43977/89A patent/AU618420B2/en not_active Expired - Fee Related
- 1989-11-02 PT PT92176A patent/PT92176B/pt not_active IP Right Cessation
- 1989-11-02 NO NO89894362A patent/NO894362L/no unknown
- 1989-11-02 KR KR1019890015850A patent/KR900007865A/ko not_active Application Discontinuation
- 1989-11-02 DK DK546689A patent/DK546689A/da not_active Application Discontinuation
- 1989-11-02 JP JP1285089A patent/JP2877253B2/ja not_active Expired - Lifetime
- 1989-11-03 ZA ZA898376A patent/ZA898376B/xx unknown
- 1989-11-03 HU HU895664A patent/HUT53677A/hu unknown
-
1996
- 1996-06-20 GR GR960401606T patent/GR3020297T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
IL92179A0 (en) | 1990-07-26 |
DE58909692D1 (de) | 1996-07-25 |
EP0367161A2 (de) | 1990-05-09 |
DK546689A (da) | 1990-05-04 |
DE3837271A1 (de) | 1990-05-10 |
ES2088883T3 (es) | 1996-10-01 |
NO894362L (no) | 1990-05-04 |
AU4397789A (en) | 1990-05-10 |
JP2877253B2 (ja) | 1999-03-31 |
AU618420B2 (en) | 1991-12-19 |
PT92176A (pt) | 1990-05-31 |
JPH02195896A (ja) | 1990-08-02 |
HU895664D0 (en) | 1990-01-28 |
KR900007865A (ko) | 1990-06-02 |
DK546689D0 (da) | 1989-11-02 |
FI895183A0 (fi) | 1989-11-01 |
NZ231221A (en) | 1991-10-25 |
NO894362D0 (no) | 1989-11-02 |
ATE139538T1 (de) | 1996-07-15 |
EP0367161B1 (de) | 1996-06-19 |
EP0367161A3 (de) | 1991-09-25 |
PT92176B (pt) | 1995-07-03 |
ZA898376B (en) | 1990-08-29 |
GR3020297T3 (en) | 1996-09-30 |
HUT53677A (en) | 1990-11-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4543329A (en) | Process for the specific cleavage of protein sequences from proteins | |
US5126249A (en) | Enzymatic removal of a protein amino-terminal sequence | |
US5691169A (en) | Process for preparing a desired protein | |
JP4291900B2 (ja) | 正しく結合したシスチン橋を有するインスリン前駆体を取得するための改良された方法 | |
US5270176A (en) | Method for the selective cleavage of fusion proteins with lysostaphin | |
Maghuin‐Rogister et al. | Luteinizing Hormone: The Primary Structures of the β‐Subunit from Bovine and Porcine Species | |
IE883893L (en) | A process for the preparation of antibodies by genetic engineering | |
US4645740A (en) | Process for enzymatic replacement of the B-30 amino acid in insulins | |
Wingard et al. | Myxobacter AL-1 protease II: specific peptide bond cleavage on the amino side of lysine | |
Ozols | Cytochrome b5 from a Normal Human Liver: ISOLATION AND THE PARTIAL AMINO ACID SEQUENCE | |
Collen et al. | Molecular biology of human plasminogen | |
US4639332A (en) | Process for the preparation of insulin derivatives | |
EP0587541B1 (en) | Process to purify the big-endothelin protein | |
Beintema et al. | The amino acid sequence of snapping turtle (Chelydra serpentina) ribonuclease | |
PH26508A (en) | A method for the selective cleavage of fusion proteins | |
Lane et al. | The sequestration, processing and retention of honey‐bee promelittin made in amphibian oocytes | |
PEMBERTON et al. | Sheep mast cell proteinase-1: characterization as a member of a new class of dual-specific ruminant chymases | |
KR20010099668A (ko) | 펩타이드의 효소적 아미드화 | |
HRP940766A2 (en) | Enzymatic process for conversion of preproinsulin to insulin | |
Kobayashi et al. | Putative ammo-terminal presequence for β-subunit of plant mitochondrial F1ATPase deduced from the amino-terminal sequence of the mature subunit | |
KR900013077A (ko) | 글루카곤의 제조방법 | |
US5130236A (en) | Process for producing des(64,65)-proinsulin | |
Kato et al. | Primary Structure of Bovine Plasma Low-Molecular-Weight Kininogen: The Complete Amino Acid Sequence of COOH-Terminal Portion Following the Bradykinin Moiety | |
Takahashi et al. | The amino acid sequence of ribonuclease U1, a guanine-specific ribonuclease from the fungus Ustilago sphaerogena | |
US5674838A (en) | Hirudin derivatives and a process for their preparation |