SK17612001A3 - Hyaluronidáza z Hirudinaria manillensis, jej izolácia, čistenie a rekombinantné spôsoby jej výroby - Google Patents

Info

Publication number

SK17612001A3

SK17612001A3 SK1761-2001A SK17612001A SK17612001A3 SK 17612001 A3 SK17612001 A3 SK 17612001A3 SK 17612001 A SK17612001 A SK 17612001A SK 17612001 A3 SK17612001 A3 SK 17612001A3

Authority

SK

Slovakia

Prior art keywords

lys

leu

protein

ser

gly

Prior art date

1999-06-12

Links

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• 102000001974 Hyaluronidases Human genes 0.000 title claims abstract description 48
• 108010003272 Hyaluronate lyase Proteins 0.000 title claims abstract description 36
• 229960002773 hyaluronidase Drugs 0.000 title claims abstract description 34
• 241000500851 Poecilobdella manillensis Species 0.000 title claims abstract description 14
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
• 238000000746 purification Methods 0.000 title abstract description 29
• 238000002955 isolation Methods 0.000 title abstract description 5
• 238000010188 recombinant method Methods 0.000 title abstract description 5
• 241000545744 Hirudinea Species 0.000 claims abstract description 27
• 238000011282 treatment Methods 0.000 claims abstract description 19
• 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 13
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 11
• 239000013604 expression vector Substances 0.000 claims abstract description 11
• 208000007536 Thrombosis Diseases 0.000 claims abstract description 5
• 208000031229 Cardiomyopathies Diseases 0.000 claims abstract description 4
• 108090000623 proteins and genes Proteins 0.000 claims description 77
• 102000004169 proteins and genes Human genes 0.000 claims description 70
• 238000000034 method Methods 0.000 claims description 33
• 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 claims description 25
• 229920000669 heparin Polymers 0.000 claims description 25
• 229960002897 heparin Drugs 0.000 claims description 24
• 239000006228 supernatant Substances 0.000 claims description 14
• 108010062580 Concanavalin A Proteins 0.000 claims description 12
• 239000002253 acid Substances 0.000 claims description 12
• 239000012634 fragment Substances 0.000 claims description 11
• 230000002255 enzymatic effect Effects 0.000 claims description 10
• 239000013598 vector Substances 0.000 claims description 10
• 238000001042 affinity chromatography Methods 0.000 claims description 9
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 8
• 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 8
• 235000011130 ammonium sulphate Nutrition 0.000 claims description 8
• 230000004071 biological effect Effects 0.000 claims description 8
• 238000004191 hydrophobic interaction chromatography Methods 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 238000005277 cation exchange chromatography Methods 0.000 claims description 7
• 230000013595 glycosylation Effects 0.000 claims description 7
• 238000006206 glycosylation reaction Methods 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 6
• 230000022811 deglycosylation Effects 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 230000002107 myocardial effect Effects 0.000 claims description 5
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 4
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 4
• 230000009471 action Effects 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 230000001376 precipitating effect Effects 0.000 claims description 3
• 241000894007 species Species 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 239000007853 buffer solution Substances 0.000 claims description 2
• 230000001419 dependent effect Effects 0.000 claims description 2
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
• 239000013543 active substance Substances 0.000 claims 2
• 238000005227 gel permeation chromatography Methods 0.000 claims 1
• 102000004190 Enzymes Human genes 0.000 abstract description 30
• 108090000790 Enzymes Proteins 0.000 abstract description 30
• 229940088598 enzyme Drugs 0.000 abstract description 30
• 238000012512 characterization method Methods 0.000 abstract description 7
• 230000001225 therapeutic effect Effects 0.000 abstract description 4
• 230000000694 effects Effects 0.000 description 69
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 21
• 239000000872 buffer Substances 0.000 description 20
• 239000000243 solution Substances 0.000 description 18
• 241000282326 Felis catus Species 0.000 description 16
• XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 16
• 108020004414 DNA Proteins 0.000 description 15
• FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 15
• VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 15
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
• 108050009363 Hyaluronidases Proteins 0.000 description 14
• 229920002684 Sepharose Polymers 0.000 description 13
• 239000000499 gel Substances 0.000 description 13
• 229920002674 hyaluronan Polymers 0.000 description 13
• 239000012528 membrane Substances 0.000 description 13
• 239000000203 mixture Substances 0.000 description 13
• 239000008363 phosphate buffer Substances 0.000 description 13
• 238000002360 preparation method Methods 0.000 description 13
• 239000011780 sodium chloride Substances 0.000 description 13
• 238000012360 testing method Methods 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• 235000013601 eggs Nutrition 0.000 description 12
• 238000011534 incubation Methods 0.000 description 12
• 239000000523 sample Substances 0.000 description 12
• 241000237902 Hirudo medicinalis Species 0.000 description 11
• GQFDWEDHOQRNLC-QWRGUYRKSA-N Lys-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN GQFDWEDHOQRNLC-QWRGUYRKSA-N 0.000 description 11
• YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 11
• 108010092854 aspartyllysine Proteins 0.000 description 11
• 230000009467 reduction Effects 0.000 description 11
• 210000001519 tissue Anatomy 0.000 description 11
• 102000001554 Hemoglobins Human genes 0.000 description 10
• 108010054147 Hemoglobins Proteins 0.000 description 10
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
• NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 9
• 229940099552 hyaluronan Drugs 0.000 description 9
• 108010009298 lysylglutamic acid Proteins 0.000 description 9
• 108010054155 lysyllysine Proteins 0.000 description 9
• XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 8
• 108010038633 aspartylglutamate Proteins 0.000 description 8
• 239000013612 plasmid Substances 0.000 description 8
• 108010080629 tryptophan-leucine Proteins 0.000 description 8
• YHZQOSXDTFRZKU-WDSOQIARSA-N Arg-Trp-Leu Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N)=CNC2=C1 YHZQOSXDTFRZKU-WDSOQIARSA-N 0.000 description 7
• IRKLTAKLAFUTLA-KATARQTJSA-N Cys-Thr-Lys Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CCCCN)C(O)=O IRKLTAKLAFUTLA-KATARQTJSA-N 0.000 description 7
• 229920002683 Glycosaminoglycan Polymers 0.000 description 7
• YCJCEMKOZOYBEF-OEAJRASXSA-N Lys-Thr-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YCJCEMKOZOYBEF-OEAJRASXSA-N 0.000 description 7
• GBEAUNVBIMLWIB-IHPCNDPISA-N Trp-Ser-Phe Chemical compound C([C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=CC=C1 GBEAUNVBIMLWIB-IHPCNDPISA-N 0.000 description 7
• ZYVAAYAOTVJBSS-GMVOTWDCSA-N Tyr-Trp-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O ZYVAAYAOTVJBSS-GMVOTWDCSA-N 0.000 description 7
• 108010005233 alanylglutamic acid Proteins 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 108010043322 lysyl-tryptophyl-alpha-lysine Proteins 0.000 description 7
• 238000000108 ultra-filtration Methods 0.000 description 7
• HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 6
• RKNIUWSZIAUEPK-PBCZWWQYSA-N Asp-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)O)N)O RKNIUWSZIAUEPK-PBCZWWQYSA-N 0.000 description 6
• HTSSXFASOUSJQG-IHPCNDPISA-N Asp-Tyr-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HTSSXFASOUSJQG-IHPCNDPISA-N 0.000 description 6
• YBAFDPFAUTYYRW-YUMQZZPRSA-N Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O YBAFDPFAUTYYRW-YUMQZZPRSA-N 0.000 description 6
• ATVYZJGOZLVXDK-IUCAKERBSA-N Glu-Leu-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O ATVYZJGOZLVXDK-IUCAKERBSA-N 0.000 description 6
• HZISRJBYZAODRV-XQXXSGGOSA-N Glu-Thr-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O HZISRJBYZAODRV-XQXXSGGOSA-N 0.000 description 6
• UQJNXZSSGQIPIQ-FBCQKBJTSA-N Gly-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)CN UQJNXZSSGQIPIQ-FBCQKBJTSA-N 0.000 description 6
• VEPBEGNDJYANCF-QWRGUYRKSA-N Gly-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN VEPBEGNDJYANCF-QWRGUYRKSA-N 0.000 description 6
• OCRQUYDOYKCOQG-IRXDYDNUSA-N Gly-Tyr-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 OCRQUYDOYKCOQG-IRXDYDNUSA-N 0.000 description 6
• REJKOQYVFDEZHA-SLBDDTMCSA-N Ile-Asp-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N REJKOQYVFDEZHA-SLBDDTMCSA-N 0.000 description 6
• HQEPKOFULQTSFV-JURCDPSOSA-N Ile-Phe-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)O)N HQEPKOFULQTSFV-JURCDPSOSA-N 0.000 description 6
• UBZGNBKMIJHOHL-BZSNNMDCSA-N Leu-Leu-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 UBZGNBKMIJHOHL-BZSNNMDCSA-N 0.000 description 6
• KPYAOIVPJKPIOU-KKUMJFAQSA-N Leu-Lys-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O KPYAOIVPJKPIOU-KKUMJFAQSA-N 0.000 description 6
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• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 6
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• 238000001262 western blot Methods 0.000 description 6
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