CA2391098C - Recombinant .alpha.-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof - Google Patents
Recombinant .alpha.-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof Download PDFInfo
- Publication number
- CA2391098C CA2391098C CA002391098A CA2391098A CA2391098C CA 2391098 C CA2391098 C CA 2391098C CA 002391098 A CA002391098 A CA 002391098A CA 2391098 A CA2391098 A CA 2391098A CA 2391098 C CA2391098 C CA 2391098C
- Authority
- CA
- Canada
- Prior art keywords
- iduronidase
- alpha
- use according
- recombinant
- subject
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 99
- 230000007812 deficiency Effects 0.000 title claims abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 23
- 201000010099 disease Diseases 0.000 title claims description 19
- 102000004190 Enzymes Human genes 0.000 claims abstract description 136
- 108090000790 Enzymes Proteins 0.000 claims abstract description 136
- 241000282414 Homo sapiens Species 0.000 claims abstract description 65
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims abstract description 34
- 239000012634 fragment Substances 0.000 claims abstract description 24
- 210000004027 cell Anatomy 0.000 claims description 100
- 239000002609 medium Substances 0.000 claims description 55
- 238000004519 manufacturing process Methods 0.000 claims description 48
- 108090000623 proteins and genes Proteins 0.000 claims description 39
- 102000004169 proteins and genes Human genes 0.000 claims description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims description 34
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 33
- 238000000746 purification Methods 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 31
- 229920002684 Sepharose Polymers 0.000 claims description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 28
- 230000007423 decrease Effects 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 25
- 210000004185 liver Anatomy 0.000 claims description 19
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 230000002485 urinary effect Effects 0.000 claims description 17
- 230000014509 gene expression Effects 0.000 claims description 16
- 238000003860 storage Methods 0.000 claims description 16
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 14
- 230000029142 excretion Effects 0.000 claims description 14
- 230000006698 induction Effects 0.000 claims description 14
- 230000002132 lysosomal effect Effects 0.000 claims description 14
- 230000010412 perfusion Effects 0.000 claims description 13
- 239000012530 fluid Substances 0.000 claims description 12
- 239000011780 sodium chloride Substances 0.000 claims description 12
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical group OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 11
- 238000004587 chromatography analysis Methods 0.000 claims description 11
- 239000010949 copper Substances 0.000 claims description 11
- 208000015204 Hurler-Scheie syndrome Diseases 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 230000012010 growth Effects 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000000872 buffer Substances 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 8
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 7
- 241000699802 Cricetulus griseus Species 0.000 claims description 7
- 208000015178 Hurler syndrome Diseases 0.000 claims description 7
- 238000001042 affinity chromatography Methods 0.000 claims description 7
- 229910052802 copper Inorganic materials 0.000 claims description 7
- 239000001963 growth medium Substances 0.000 claims description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 7
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 7
- 229940068968 polysorbate 80 Drugs 0.000 claims description 7
- 229920000053 polysorbate 80 Polymers 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 210000000952 spleen Anatomy 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000012091 fetal bovine serum Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000003306 harvesting Methods 0.000 claims description 5
- 210000001672 ovary Anatomy 0.000 claims description 5
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 claims description 5
- 239000012064 sodium phosphate buffer Substances 0.000 claims description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 4
- 230000004071 biological effect Effects 0.000 claims description 4
- 238000011026 diafiltration Methods 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000011084 recovery Methods 0.000 claims description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 3
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 3
- 239000001045 blue dye Substances 0.000 claims description 3
- YKCWQPZFAFZLBI-UHFFFAOYSA-N cibacron blue Chemical compound C1=2C(=O)C3=CC=CC=C3C(=O)C=2C(N)=C(S(O)(=O)=O)C=C1NC(C=C1S(O)(=O)=O)=CC=C1NC(N=1)=NC(Cl)=NC=1NC1=CC=CC=C1S(O)(=O)=O YKCWQPZFAFZLBI-UHFFFAOYSA-N 0.000 claims description 3
- 230000000295 complement effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 238000000108 ultra-filtration Methods 0.000 claims description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000011081 inoculation Methods 0.000 claims description 2
- 238000005086 pumping Methods 0.000 claims description 2
- 229940104230 thymidine Drugs 0.000 claims description 2
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims 4
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims 4
- 230000001154 acute effect Effects 0.000 claims 2
- 230000000172 allergic effect Effects 0.000 claims 2
- 208000010668 atopic eczema Diseases 0.000 claims 2
- 239000013522 chelant Substances 0.000 claims 2
- 238000011210 chromatographic step Methods 0.000 claims 2
- 239000012504 chromatography matrix Substances 0.000 claims 2
- 229910021645 metal ion Inorganic materials 0.000 claims 2
- 229920000136 polysorbate Polymers 0.000 claims 2
- 229950008882 polysorbate Drugs 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 229910001431 copper ion Inorganic materials 0.000 claims 1
- 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 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 239000002953 phosphate buffered saline Substances 0.000 claims 1
- 230000001502 supplementing effect Effects 0.000 claims 1
- 230000014616 translation Effects 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 208000026350 Inborn Genetic disease Diseases 0.000 abstract description 2
- 208000016361 genetic disease Diseases 0.000 abstract description 2
- 229940088598 enzyme Drugs 0.000 description 129
- 235000018102 proteins Nutrition 0.000 description 30
- 238000002560 therapeutic procedure Methods 0.000 description 29
- 239000002299 complementary DNA Substances 0.000 description 21
- 230000001965 increasing effect Effects 0.000 description 20
- 230000006872 improvement Effects 0.000 description 18
- 210000001519 tissue Anatomy 0.000 description 16
- 150000001413 amino acids Chemical group 0.000 description 15
- 150000001720 carbohydrates Chemical class 0.000 description 15
- 235000014633 carbohydrates Nutrition 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 14
- 230000003247 decreasing effect Effects 0.000 description 14
- 230000001225 therapeutic effect Effects 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 241000282472 Canis lupus familiaris Species 0.000 description 13
- 102000004627 Iduronidase Human genes 0.000 description 13
- 108010003381 Iduronidase Proteins 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 13
- 239000013604 expression vector Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 230000008569 process Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000001913 cellulose Substances 0.000 description 8
- 229920002678 cellulose Polymers 0.000 description 8
- 238000002641 enzyme replacement therapy Methods 0.000 description 8
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 7
- 206010021079 Hypopnoea Diseases 0.000 description 7
- 208000008784 apnea Diseases 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 241000282326 Felis catus Species 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- 239000013543 active substance Substances 0.000 description 6
- 230000006978 adaptation Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 210000002950 fibroblast Anatomy 0.000 description 6
- 108010000761 leucylarginine Proteins 0.000 description 6
- 230000033001 locomotion Effects 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 239000005549 deoxyribonucleoside Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 108010050848 glycylleucine Proteins 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 108010029020 prolylglycine Proteins 0.000 description 5
- 239000002342 ribonucleoside Substances 0.000 description 5
- 108010026333 seryl-proline Proteins 0.000 description 5
- 230000007958 sleep Effects 0.000 description 5
- YBZMTKUDWXZLIX-UWVGGRQHSA-N Arg-Leu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YBZMTKUDWXZLIX-UWVGGRQHSA-N 0.000 description 4
- 241000282465 Canis Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-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
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 4
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 4
- 108010006025 bovine growth hormone Proteins 0.000 description 4
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 4
- -1 cellulose Chemical class 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000011109 contamination Methods 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
- 230000002068 genetic effect Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 210000003127 knee Anatomy 0.000 description 4
- 238000011031 large-scale manufacturing process Methods 0.000 description 4
- 108010057821 leucylproline Proteins 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000003712 lysosome Anatomy 0.000 description 4
- 230000001868 lysosomic effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000013587 production medium Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- YYOVLDPHIJAOSY-DCAQKATOSA-N Arg-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N YYOVLDPHIJAOSY-DCAQKATOSA-N 0.000 description 3
- 108010062580 Concanavalin A Proteins 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 229920000045 Dermatan sulfate Polymers 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 229920002971 Heparan sulfate Polymers 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- IFMDQWDAJUMMJC-DCAQKATOSA-N Pro-Ala-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O IFMDQWDAJUMMJC-DCAQKATOSA-N 0.000 description 3
- BSCBBPKDVOZICB-KKUMJFAQSA-N Tyr-Leu-Asp 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(O)=O)C(O)=O BSCBBPKDVOZICB-KKUMJFAQSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 108010060035 arginylproline Proteins 0.000 description 3
- 229940009098 aspartate Drugs 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000024203 complement activation Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 3
- 229940051593 dermatan sulfate Drugs 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000006167 equilibration buffer Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 230000008105 immune reaction Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000001155 isoelectric focusing Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 108010051242 phenylalanylserine Proteins 0.000 description 3
- 239000012557 regeneration buffer Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 230000000153 supplemental effect Effects 0.000 description 3
- 108010061238 threonyl-glycine Proteins 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 2
- 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 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- ZFXQNADNEBRERM-BJDJZHNGSA-N Ala-Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 ZFXQNADNEBRERM-BJDJZHNGSA-N 0.000 description 2
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 2
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 2
- BGNLUHXLSAQYRQ-FXQIFTODSA-N Ala-Glu-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BGNLUHXLSAQYRQ-FXQIFTODSA-N 0.000 description 2
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 2
- ZPXCNXMJEZKRLU-LSJOCFKGSA-N Ala-His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CN=CN1 ZPXCNXMJEZKRLU-LSJOCFKGSA-N 0.000 description 2
- OMDNCNKNEGFOMM-BQBZGAKWSA-N Ala-Met-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O OMDNCNKNEGFOMM-BQBZGAKWSA-N 0.000 description 2
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 2
- YEBZNKPPOHFZJM-BPNCWPANSA-N Ala-Tyr-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O YEBZNKPPOHFZJM-BPNCWPANSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 229920000945 Amylopectin Polymers 0.000 description 2
- YFWTXMRJJDNTLM-LSJOCFKGSA-N Arg-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YFWTXMRJJDNTLM-LSJOCFKGSA-N 0.000 description 2
- ZATRYQNPUHGXCU-DTWKUNHWSA-N Arg-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ZATRYQNPUHGXCU-DTWKUNHWSA-N 0.000 description 2
- LVMUGODRNHFGRA-AVGNSLFASA-N Arg-Leu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O LVMUGODRNHFGRA-AVGNSLFASA-N 0.000 description 2
- NMRHDSAOIURTNT-RWMBFGLXSA-N Arg-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NMRHDSAOIURTNT-RWMBFGLXSA-N 0.000 description 2
- GRRXPUAICOGISM-RWMBFGLXSA-N Arg-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GRRXPUAICOGISM-RWMBFGLXSA-N 0.000 description 2
- XFXZKCRBBOVJKS-BVSLBCMMSA-N Arg-Phe-Trp Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 XFXZKCRBBOVJKS-BVSLBCMMSA-N 0.000 description 2
- XSPKAHFVDKRGRL-DCAQKATOSA-N Arg-Pro-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XSPKAHFVDKRGRL-DCAQKATOSA-N 0.000 description 2
- 108010051330 Arg-Pro-Gly-Pro Proteins 0.000 description 2
- NGYHSXDNNOFHNE-AVGNSLFASA-N Arg-Pro-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O NGYHSXDNNOFHNE-AVGNSLFASA-N 0.000 description 2
- VUGWHBXPMAHEGZ-SRVKXCTJSA-N Arg-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N VUGWHBXPMAHEGZ-SRVKXCTJSA-N 0.000 description 2
- SUEIIIFUBHDCCS-PBCZWWQYSA-N Asn-His-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SUEIIIFUBHDCCS-PBCZWWQYSA-N 0.000 description 2
- LRCIOEVFVGXZKB-BZSNNMDCSA-N Asn-Tyr-Tyr 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](CC1=CC=C(O)C=C1)C(O)=O LRCIOEVFVGXZKB-BZSNNMDCSA-N 0.000 description 2
- GBAWQWASNGUNQF-ZLUOBGJFSA-N Asp-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N GBAWQWASNGUNQF-ZLUOBGJFSA-N 0.000 description 2
- BFOYULZBKYOKAN-OLHMAJIHSA-N Asp-Asp-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BFOYULZBKYOKAN-OLHMAJIHSA-N 0.000 description 2
- LJRPYAZQQWHEEV-FXQIFTODSA-N Asp-Gln-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O LJRPYAZQQWHEEV-FXQIFTODSA-N 0.000 description 2
- GWIJZUVQVDJHDI-AVGNSLFASA-N Asp-Phe-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O GWIJZUVQVDJHDI-AVGNSLFASA-N 0.000 description 2
- ZQFRDAZBTSFGGW-SRVKXCTJSA-N Asp-Ser-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZQFRDAZBTSFGGW-SRVKXCTJSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- WQWMZOIPXWSZNE-WDSKDSINSA-N Gln-Asp-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O WQWMZOIPXWSZNE-WDSKDSINSA-N 0.000 description 2
- UESYBOXFJWJVSB-AVGNSLFASA-N Gln-Phe-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O UESYBOXFJWJVSB-AVGNSLFASA-N 0.000 description 2
- MLCPTRRNICEKIS-FXQIFTODSA-N Glu-Asn-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MLCPTRRNICEKIS-FXQIFTODSA-N 0.000 description 2
- PVBBEKPHARMPHX-DCAQKATOSA-N Glu-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCC(O)=O PVBBEKPHARMPHX-DCAQKATOSA-N 0.000 description 2
- JRDYDYXZKFNNRQ-XPUUQOCRSA-N Gly-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN JRDYDYXZKFNNRQ-XPUUQOCRSA-N 0.000 description 2
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 2
- XRTDOIOIBMAXCT-NKWVEPMBSA-N Gly-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)CN)C(=O)O XRTDOIOIBMAXCT-NKWVEPMBSA-N 0.000 description 2
- QPDUVFSVVAOUHE-XVKPBYJWSA-N Gly-Gln-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)CN)C(O)=O QPDUVFSVVAOUHE-XVKPBYJWSA-N 0.000 description 2
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 description 2
- IXHQLZIWBCQBLQ-STQMWFEESA-N Gly-Pro-Phe Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IXHQLZIWBCQBLQ-STQMWFEESA-N 0.000 description 2
- YGHSQRJSHKYUJY-SCZZXKLOSA-N Gly-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN YGHSQRJSHKYUJY-SCZZXKLOSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- PROLDOGUBQJNPG-RWMBFGLXSA-N His-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O PROLDOGUBQJNPG-RWMBFGLXSA-N 0.000 description 2
- JSQIXEHORHLQEE-MEYUZBJRSA-N His-Phe-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JSQIXEHORHLQEE-MEYUZBJRSA-N 0.000 description 2
- CGAMSLMBYJHMDY-ONGXEEELSA-N His-Val-Gly Chemical compound CC(C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CN=CN1)N CGAMSLMBYJHMDY-ONGXEEELSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 206010023230 Joint stiffness Diseases 0.000 description 2
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 2
- SUPVSFFZWVOEOI-UHFFFAOYSA-N Leu-Ala-Tyr Natural products CC(C)CC(N)C(=O)NC(C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 SUPVSFFZWVOEOI-UHFFFAOYSA-N 0.000 description 2
- NTRAGDHVSGKUSF-AVGNSLFASA-N Leu-Arg-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NTRAGDHVSGKUSF-AVGNSLFASA-N 0.000 description 2
- FJUKMPUELVROGK-IHRRRGAJSA-N Leu-Arg-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N FJUKMPUELVROGK-IHRRRGAJSA-N 0.000 description 2
- IBMVEYRWAWIOTN-RWMBFGLXSA-N Leu-Arg-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(O)=O IBMVEYRWAWIOTN-RWMBFGLXSA-N 0.000 description 2
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 2
- ILJREDZFPHTUIE-GUBZILKMSA-N Leu-Asp-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ILJREDZFPHTUIE-GUBZILKMSA-N 0.000 description 2
- ULXYQAJWJGLCNR-YUMQZZPRSA-N Leu-Asp-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O ULXYQAJWJGLCNR-YUMQZZPRSA-N 0.000 description 2
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 2
- QLQHWWCSCLZUMA-KKUMJFAQSA-N Leu-Asp-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QLQHWWCSCLZUMA-KKUMJFAQSA-N 0.000 description 2
- HVJVUYQWFYMGJS-GVXVVHGQSA-N Leu-Glu-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVJVUYQWFYMGJS-GVXVVHGQSA-N 0.000 description 2
- DSFYPIUSAMSERP-IHRRRGAJSA-N Leu-Leu-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DSFYPIUSAMSERP-IHRRRGAJSA-N 0.000 description 2
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 2
- UCBPDSYUVAAHCD-UWVGGRQHSA-N Leu-Pro-Gly Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UCBPDSYUVAAHCD-UWVGGRQHSA-N 0.000 description 2
- HWMQRQIFVGEAPH-XIRDDKMYSA-N Leu-Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 HWMQRQIFVGEAPH-XIRDDKMYSA-N 0.000 description 2
- SUYRAPCRSCCPAK-VFAJRCTISA-N Leu-Trp-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SUYRAPCRSCCPAK-VFAJRCTISA-N 0.000 description 2
- LMDVGHQPPPLYAR-IHRRRGAJSA-N Leu-Val-His Chemical compound N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O LMDVGHQPPPLYAR-IHRRRGAJSA-N 0.000 description 2
- NTXYXFDMIHXTHE-WDSOQIARSA-N Leu-Val-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 NTXYXFDMIHXTHE-WDSOQIARSA-N 0.000 description 2
- VHXMZJGOKIMETG-CQDKDKBSSA-N Lys-Ala-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCCCN)N VHXMZJGOKIMETG-CQDKDKBSSA-N 0.000 description 2
- UQJOKDAYFULYIX-AVGNSLFASA-N Lys-Pro-Pro Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 UQJOKDAYFULYIX-AVGNSLFASA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- DLAFCQWUMFMZSN-GUBZILKMSA-N Met-Arg-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CCCN=C(N)N DLAFCQWUMFMZSN-GUBZILKMSA-N 0.000 description 2
- LRALLISKBZNSKN-BQBZGAKWSA-N Met-Gly-Ser Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LRALLISKBZNSKN-BQBZGAKWSA-N 0.000 description 2
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 2
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- LZDIENNKWVXJMX-JYJNAYRXSA-N Phe-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC1=CC=CC=C1 LZDIENNKWVXJMX-JYJNAYRXSA-N 0.000 description 2
- KJJROSNFBRWPHS-JYJNAYRXSA-N Phe-Glu-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KJJROSNFBRWPHS-JYJNAYRXSA-N 0.000 description 2
- XOHJOMKCRLHGCY-UNQGMJICSA-N Phe-Pro-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOHJOMKCRLHGCY-UNQGMJICSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- APKRGYLBSCWJJP-FXQIFTODSA-N Pro-Ala-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O APKRGYLBSCWJJP-FXQIFTODSA-N 0.000 description 2
- CYQQWUPHIZVCNY-GUBZILKMSA-N Pro-Arg-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CYQQWUPHIZVCNY-GUBZILKMSA-N 0.000 description 2
- VPVHXWGPALPDGP-GUBZILKMSA-N Pro-Asn-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VPVHXWGPALPDGP-GUBZILKMSA-N 0.000 description 2
- STASJMBVVHNWCG-IHRRRGAJSA-N Pro-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 STASJMBVVHNWCG-IHRRRGAJSA-N 0.000 description 2
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 2
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 2
- SNGZLPOXVRTNMB-LPEHRKFASA-N Pro-Ser-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N2CCC[C@@H]2C(=O)O SNGZLPOXVRTNMB-LPEHRKFASA-N 0.000 description 2
- XDKKMRPRRCOELJ-GUBZILKMSA-N Pro-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 XDKKMRPRRCOELJ-GUBZILKMSA-N 0.000 description 2
- ZMLRZBWCXPQADC-TUAOUCFPSA-N Pro-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 ZMLRZBWCXPQADC-TUAOUCFPSA-N 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 201000002883 Scheie syndrome Diseases 0.000 description 2
- 239000012506 Sephacryl® Substances 0.000 description 2
- FTVRVZNYIYWJGB-ACZMJKKPSA-N Ser-Asp-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FTVRVZNYIYWJGB-ACZMJKKPSA-N 0.000 description 2
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 2
- YRBGKVIWMNEVCZ-WDSKDSINSA-N Ser-Glu-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O YRBGKVIWMNEVCZ-WDSKDSINSA-N 0.000 description 2
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 2
- JLPMFVAIQHCBDC-CIUDSAMLSA-N Ser-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N JLPMFVAIQHCBDC-CIUDSAMLSA-N 0.000 description 2
- PJIQEIFXZPCWOJ-FXQIFTODSA-N Ser-Pro-Asp Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O PJIQEIFXZPCWOJ-FXQIFTODSA-N 0.000 description 2
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- VFEHSAJCWWHDBH-RHYQMDGZSA-N Thr-Arg-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VFEHSAJCWWHDBH-RHYQMDGZSA-N 0.000 description 2
- PUEWAXRPXOEQOW-HJGDQZAQSA-N Thr-Met-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(O)=O PUEWAXRPXOEQOW-HJGDQZAQSA-N 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- QAXCHNZDPLSFPC-PJODQICGSA-N Trp-Ala-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 QAXCHNZDPLSFPC-PJODQICGSA-N 0.000 description 2
- MQVGIFJSFFVGFW-XEGUGMAKSA-N Trp-Ala-Glu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MQVGIFJSFFVGFW-XEGUGMAKSA-N 0.000 description 2
- HOJPPPKZWFRTHJ-PJODQICGSA-N Trp-Arg-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N HOJPPPKZWFRTHJ-PJODQICGSA-N 0.000 description 2
- RPVDDQYNBOVWLR-HOCLYGCPSA-N Trp-Gly-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O RPVDDQYNBOVWLR-HOCLYGCPSA-N 0.000 description 2
- LGEYOIQBBIPHQN-UWJYBYFXSA-N Tyr-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 LGEYOIQBBIPHQN-UWJYBYFXSA-N 0.000 description 2
- IMXAAEFAIBRCQF-SIUGBPQLSA-N Tyr-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N IMXAAEFAIBRCQF-SIUGBPQLSA-N 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 108010064997 VPY tripeptide Proteins 0.000 description 2
- ZLFHAAGHGQBQQN-AEJSXWLSSA-N Val-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZLFHAAGHGQBQQN-AEJSXWLSSA-N 0.000 description 2
- ZLFHAAGHGQBQQN-GUBZILKMSA-N Val-Ala-Pro Natural products CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O ZLFHAAGHGQBQQN-GUBZILKMSA-N 0.000 description 2
- CWSIBTLMMQLPPZ-FXQIFTODSA-N Val-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N CWSIBTLMMQLPPZ-FXQIFTODSA-N 0.000 description 2
- XXROXFHCMVXETG-UWVGGRQHSA-N Val-Gly-Val Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXROXFHCMVXETG-UWVGGRQHSA-N 0.000 description 2
- CPGJELLYDQEDRK-NAKRPEOUSA-N Val-Ile-Ala Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](C)C(O)=O CPGJELLYDQEDRK-NAKRPEOUSA-N 0.000 description 2
- DAVNYIUELQBTAP-XUXIUFHCSA-N Val-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N DAVNYIUELQBTAP-XUXIUFHCSA-N 0.000 description 2
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 2
- QWCZXKIFPWPQHR-JYJNAYRXSA-N Val-Pro-Tyr Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QWCZXKIFPWPQHR-JYJNAYRXSA-N 0.000 description 2
- RYHUIHUOYRNNIE-NRPADANISA-N Val-Ser-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RYHUIHUOYRNNIE-NRPADANISA-N 0.000 description 2
- LCHZBEUVGAVMKS-RHYQMDGZSA-N Val-Thr-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(O)=O LCHZBEUVGAVMKS-RHYQMDGZSA-N 0.000 description 2
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 2
- 229940124532 absorption promoter Drugs 0.000 description 2
- 108010081404 acein-2 Proteins 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 108010066829 alanyl-glutamyl-aspartylprolyine Proteins 0.000 description 2
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 2
- 108010087924 alanylproline Proteins 0.000 description 2
- 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 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 2
- 108010047857 aspartylglycine Proteins 0.000 description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 230000001680 brushing effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 238000011833 dog model Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012537 formulation buffer Substances 0.000 description 2
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 108010078144 glutaminyl-glycine Proteins 0.000 description 2
- HPAIKDPJURGQLN-UHFFFAOYSA-N glycyl-L-histidyl-L-phenylalanine Natural products C=1C=CC=CC=1CC(C(O)=O)NC(=O)C(NC(=O)CN)CC1=CN=CN1 HPAIKDPJURGQLN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012633 leachable Substances 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 2
- 108010030617 leucyl-phenylalanyl-valine Proteins 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000007030 peptide scission Effects 0.000 description 2
- 108010082795 phenylalanyl-arginyl-arginine Proteins 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108010004914 prolylarginine Proteins 0.000 description 2
- 108010053725 prolylvaline Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BRPMXFSTKXXNHF-IUCAKERBSA-N (2s)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H]1NCCC1 BRPMXFSTKXXNHF-IUCAKERBSA-N 0.000 description 1
- PHOLIFLKGONSGY-CSKARUKUSA-N (e)-(3-methyl-1,3-benzothiazol-2-ylidene)hydrazine Chemical compound C1=CC=C2S\C(=N\N)N(C)C2=C1 PHOLIFLKGONSGY-CSKARUKUSA-N 0.000 description 1
- KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical class CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-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
- 244000215068 Acacia senegal Species 0.000 description 1
- VBDMWOKJZDCFJM-FXQIFTODSA-N Ala-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N VBDMWOKJZDCFJM-FXQIFTODSA-N 0.000 description 1
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 1
- ODWSTKXGQGYHSH-FXQIFTODSA-N Ala-Arg-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O ODWSTKXGQGYHSH-FXQIFTODSA-N 0.000 description 1
- CXQODNIBUNQWAS-CIUDSAMLSA-N Ala-Gln-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CXQODNIBUNQWAS-CIUDSAMLSA-N 0.000 description 1
- RXTBLQVXNIECFP-FXQIFTODSA-N Ala-Gln-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RXTBLQVXNIECFP-FXQIFTODSA-N 0.000 description 1
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 1
- HJGZVLLLBJLXFC-LSJOCFKGSA-N Ala-His-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(O)=O HJGZVLLLBJLXFC-LSJOCFKGSA-N 0.000 description 1
- LBYMZCVBOKYZNS-CIUDSAMLSA-N Ala-Leu-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O LBYMZCVBOKYZNS-CIUDSAMLSA-N 0.000 description 1
- ZKEHTYWGPMMGBC-XUXIUFHCSA-N Ala-Leu-Leu-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O ZKEHTYWGPMMGBC-XUXIUFHCSA-N 0.000 description 1
- ZBLQIYPCUWZSRZ-QEJZJMRPSA-N Ala-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 ZBLQIYPCUWZSRZ-QEJZJMRPSA-N 0.000 description 1
- OSRZOHXQCUFIQG-FPMFFAJLSA-N Ala-Phe-Pro Chemical compound C([C@H](NC(=O)[C@@H]([NH3+])C)C(=O)N1[C@H](CCC1)C([O-])=O)C1=CC=CC=C1 OSRZOHXQCUFIQG-FPMFFAJLSA-N 0.000 description 1
- MAZZQZWCCYJQGZ-GUBZILKMSA-N Ala-Pro-Arg Chemical compound [H]N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MAZZQZWCCYJQGZ-GUBZILKMSA-N 0.000 description 1
- AETQNIIFKCMVHP-UVBJJODRSA-N Ala-Trp-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AETQNIIFKCMVHP-UVBJJODRSA-N 0.000 description 1
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- MCYJBCKCAPERSE-FXQIFTODSA-N Arg-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N MCYJBCKCAPERSE-FXQIFTODSA-N 0.000 description 1
- YUIGJDNAGKJLDO-JYJNAYRXSA-N Arg-Arg-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YUIGJDNAGKJLDO-JYJNAYRXSA-N 0.000 description 1
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 1
- JEOCWTUOMKEEMF-RHYQMDGZSA-N Arg-Leu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JEOCWTUOMKEEMF-RHYQMDGZSA-N 0.000 description 1
- VEAIMHJZTIDCIH-KKUMJFAQSA-N Arg-Phe-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEAIMHJZTIDCIH-KKUMJFAQSA-N 0.000 description 1
- WKPXXXUSUHAXDE-SRVKXCTJSA-N Arg-Pro-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O WKPXXXUSUHAXDE-SRVKXCTJSA-N 0.000 description 1
- FRBAHXABMQXSJQ-FXQIFTODSA-N Arg-Ser-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O FRBAHXABMQXSJQ-FXQIFTODSA-N 0.000 description 1
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 1
- RYQSYXFGFOTJDJ-RHYQMDGZSA-N Arg-Thr-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O RYQSYXFGFOTJDJ-RHYQMDGZSA-N 0.000 description 1
- UVTGNSWSRSCPLP-UHFFFAOYSA-N Arg-Tyr Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O UVTGNSWSRSCPLP-UHFFFAOYSA-N 0.000 description 1
- QJWLLRZTJFPCHA-STECZYCISA-N Arg-Tyr-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O QJWLLRZTJFPCHA-STECZYCISA-N 0.000 description 1
- CGWVCWFQGXOUSJ-ULQDDVLXSA-N Arg-Tyr-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O CGWVCWFQGXOUSJ-ULQDDVLXSA-N 0.000 description 1
- ISVACHFCVRKIDG-SRVKXCTJSA-N Arg-Val-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O ISVACHFCVRKIDG-SRVKXCTJSA-N 0.000 description 1
- 102100031491 Arylsulfatase B Human genes 0.000 description 1
- PIWWUBYJNONVTJ-ZLUOBGJFSA-N Asn-Asp-Asn Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)C(=O)N PIWWUBYJNONVTJ-ZLUOBGJFSA-N 0.000 description 1
- BKDDABUWNKGZCK-XHNCKOQMSA-N Asn-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)N)C(=O)O BKDDABUWNKGZCK-XHNCKOQMSA-N 0.000 description 1
- HYQYLOSCICEYTR-YUMQZZPRSA-N Asn-Gly-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O HYQYLOSCICEYTR-YUMQZZPRSA-N 0.000 description 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 description 1
- JEEFEQCRXKPQHC-KKUMJFAQSA-N Asn-Leu-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JEEFEQCRXKPQHC-KKUMJFAQSA-N 0.000 description 1
- RAUPFUCUDBQYHE-AVGNSLFASA-N Asn-Phe-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RAUPFUCUDBQYHE-AVGNSLFASA-N 0.000 description 1
- BKFXFUPYETWGGA-XVSYOHENSA-N Asn-Phe-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BKFXFUPYETWGGA-XVSYOHENSA-N 0.000 description 1
- JXMREEPBRANWBY-VEVYYDQMSA-N Asn-Thr-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JXMREEPBRANWBY-VEVYYDQMSA-N 0.000 description 1
- PQKSVQSMTHPRIB-ZKWXMUAHSA-N Asn-Val-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O PQKSVQSMTHPRIB-ZKWXMUAHSA-N 0.000 description 1
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 1
- YNQIDCRRTWGHJD-ZLUOBGJFSA-N Asp-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(O)=O YNQIDCRRTWGHJD-ZLUOBGJFSA-N 0.000 description 1
- GWTLRDMPMJCNMH-WHFBIAKZSA-N Asp-Asn-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GWTLRDMPMJCNMH-WHFBIAKZSA-N 0.000 description 1
- UFAQGGZUXVLONR-AVGNSLFASA-N Asp-Gln-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N)O UFAQGGZUXVLONR-AVGNSLFASA-N 0.000 description 1
- VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 1
- WYOSXGYAKZQPGF-SRVKXCTJSA-N Asp-His-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC(=O)O)N WYOSXGYAKZQPGF-SRVKXCTJSA-N 0.000 description 1
- CZECQDPEMSVPDH-MNXVOIDGSA-N Asp-Leu-Val-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O CZECQDPEMSVPDH-MNXVOIDGSA-N 0.000 description 1
- QNIACYURSSCLRP-GUBZILKMSA-N Asp-Lys-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O QNIACYURSSCLRP-GUBZILKMSA-N 0.000 description 1
- WOPJVEMFXYHZEE-SRVKXCTJSA-N Asp-Phe-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O WOPJVEMFXYHZEE-SRVKXCTJSA-N 0.000 description 1
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 1
- JJQGZGOEDSSHTE-FOHZUACHSA-N Asp-Thr-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JJQGZGOEDSSHTE-FOHZUACHSA-N 0.000 description 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 description 1
- RKXVTTIQNKPCHU-KKHAAJSZSA-N Asp-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O RKXVTTIQNKPCHU-KKHAAJSZSA-N 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010010725 Conjunctival irritation Diseases 0.000 description 1
- 208000006069 Corneal Opacity Diseases 0.000 description 1
- ANRWXLYGJRSQEQ-CIUDSAMLSA-N Cys-His-Asp Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O ANRWXLYGJRSQEQ-CIUDSAMLSA-N 0.000 description 1
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 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 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- REJJNXODKSHOKA-ACZMJKKPSA-N Gln-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N REJJNXODKSHOKA-ACZMJKKPSA-N 0.000 description 1
- CLPQUWHBWXFJOX-BQBZGAKWSA-N Gln-Gly-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O CLPQUWHBWXFJOX-BQBZGAKWSA-N 0.000 description 1
- PODFFOWWLUPNMN-DCAQKATOSA-N Gln-His-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PODFFOWWLUPNMN-DCAQKATOSA-N 0.000 description 1
- TWTWUBHEWQPMQW-ZPFDUUQYSA-N Gln-Ile-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TWTWUBHEWQPMQW-ZPFDUUQYSA-N 0.000 description 1
- XFAUJGNLHIGXET-AVGNSLFASA-N Gln-Leu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XFAUJGNLHIGXET-AVGNSLFASA-N 0.000 description 1
- SHAUZYVSXAMYAZ-JYJNAYRXSA-N Gln-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](CCC(=O)N)N SHAUZYVSXAMYAZ-JYJNAYRXSA-N 0.000 description 1
- FGWRYRAVBVOHIB-XIRDDKMYSA-N Gln-Pro-Trp Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O FGWRYRAVBVOHIB-XIRDDKMYSA-N 0.000 description 1
- SJMJMEWQMBJYPR-DZKIICNBSA-N Gln-Tyr-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)N)N SJMJMEWQMBJYPR-DZKIICNBSA-N 0.000 description 1
- OACPJRQRAHMQEQ-NHCYSSNCSA-N Gln-Val-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OACPJRQRAHMQEQ-NHCYSSNCSA-N 0.000 description 1
- ICRKQMRFXYDYMK-LAEOZQHASA-N Gln-Val-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O ICRKQMRFXYDYMK-LAEOZQHASA-N 0.000 description 1
- ZMXZGYLINVNTKH-DZKIICNBSA-N Gln-Val-Phe Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZMXZGYLINVNTKH-DZKIICNBSA-N 0.000 description 1
- WZZSKAJIHTUUSG-ACZMJKKPSA-N Glu-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O WZZSKAJIHTUUSG-ACZMJKKPSA-N 0.000 description 1
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 1
- XHUCVVHRLNPZSZ-CIUDSAMLSA-N Glu-Gln-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XHUCVVHRLNPZSZ-CIUDSAMLSA-N 0.000 description 1
- SUIAHERNFYRBDZ-GVXVVHGQSA-N Glu-Lys-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O SUIAHERNFYRBDZ-GVXVVHGQSA-N 0.000 description 1
- UDEPRBFQTWGLCW-CIUDSAMLSA-N Glu-Pro-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O UDEPRBFQTWGLCW-CIUDSAMLSA-N 0.000 description 1
- QVXWAFZDWRLXTI-NWLDYVSISA-N Glu-Thr-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O QVXWAFZDWRLXTI-NWLDYVSISA-N 0.000 description 1
- JDAYMLXPUJRSDJ-XIRDDKMYSA-N Glu-Trp-Arg Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 JDAYMLXPUJRSDJ-XIRDDKMYSA-N 0.000 description 1
- YOTHMZZSJKKEHZ-SZMVWBNQSA-N Glu-Trp-Lys Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CCC(O)=O)=CNC2=C1 YOTHMZZSJKKEHZ-SZMVWBNQSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 description 1
- RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 1
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 1
- XUORRGAFUQIMLC-STQMWFEESA-N Gly-Arg-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CN)O XUORRGAFUQIMLC-STQMWFEESA-N 0.000 description 1
- LXXANCRPFBSSKS-IUCAKERBSA-N Gly-Gln-Leu Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LXXANCRPFBSSKS-IUCAKERBSA-N 0.000 description 1
- MOJKRXIRAZPZLW-WDSKDSINSA-N Gly-Glu-Ala Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O MOJKRXIRAZPZLW-WDSKDSINSA-N 0.000 description 1
- JNGJGFMFXREJNF-KBPBESRZSA-N Gly-Glu-Trp Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JNGJGFMFXREJNF-KBPBESRZSA-N 0.000 description 1
- ITZOBNKQDZEOCE-NHCYSSNCSA-N Gly-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)CN ITZOBNKQDZEOCE-NHCYSSNCSA-N 0.000 description 1
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 1
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 1
- QVDGHDFFYHKJPN-QWRGUYRKSA-N Gly-Phe-Cys Chemical compound NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CS)C(O)=O QVDGHDFFYHKJPN-QWRGUYRKSA-N 0.000 description 1
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 1
- FKYQEVBRZSFAMJ-QWRGUYRKSA-N Gly-Ser-Tyr Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FKYQEVBRZSFAMJ-QWRGUYRKSA-N 0.000 description 1
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 1
- GJHWILMUOANXTG-WPRPVWTQSA-N Gly-Val-Arg Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GJHWILMUOANXTG-WPRPVWTQSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- ZIMTWPHIKZEHSE-UWVGGRQHSA-N His-Arg-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O ZIMTWPHIKZEHSE-UWVGGRQHSA-N 0.000 description 1
- MWAJSVTZZOUOBU-IHRRRGAJSA-N His-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC1=CN=CN1 MWAJSVTZZOUOBU-IHRRRGAJSA-N 0.000 description 1
- LSQHWKPPOFDHHZ-YUMQZZPRSA-N His-Asp-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N LSQHWKPPOFDHHZ-YUMQZZPRSA-N 0.000 description 1
- VYMGAXSNYUFVCK-GUBZILKMSA-N His-Gln-Asn Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N VYMGAXSNYUFVCK-GUBZILKMSA-N 0.000 description 1
- KAFZDWMZKGQDEE-SRVKXCTJSA-N His-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KAFZDWMZKGQDEE-SRVKXCTJSA-N 0.000 description 1
- PBVQWNDMFFCPIZ-ULQDDVLXSA-N His-Pro-Phe Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 PBVQWNDMFFCPIZ-ULQDDVLXSA-N 0.000 description 1
- LNVILFYCPVOHPV-IHPCNDPISA-N His-Trp-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O LNVILFYCPVOHPV-IHPCNDPISA-N 0.000 description 1
- XGBVLRJLHUVCNK-DCAQKATOSA-N His-Val-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O XGBVLRJLHUVCNK-DCAQKATOSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 description 1
- 101710096421 Iduronate 2-sulfatase Proteins 0.000 description 1
- ASCFJMSGKUIRDU-ZPFDUUQYSA-N Ile-Arg-Gln Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O ASCFJMSGKUIRDU-ZPFDUUQYSA-N 0.000 description 1
- NHJKZMDIMMTVCK-QXEWZRGKSA-N Ile-Gly-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N NHJKZMDIMMTVCK-QXEWZRGKSA-N 0.000 description 1
- PNTWNAXGBOZMBO-MNXVOIDGSA-N Ile-Lys-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PNTWNAXGBOZMBO-MNXVOIDGSA-N 0.000 description 1
- AGGIYSLVUKVOPT-HTFCKZLJSA-N Ile-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N AGGIYSLVUKVOPT-HTFCKZLJSA-N 0.000 description 1
- PELCGFMHLZXWBQ-BJDJZHNGSA-N Ile-Ser-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)O)N PELCGFMHLZXWBQ-BJDJZHNGSA-N 0.000 description 1
- FXJLRZFMKGHYJP-CFMVVWHZSA-N Ile-Tyr-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N FXJLRZFMKGHYJP-CFMVVWHZSA-N 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 208000024781 Immune Complex disease Diseases 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241001466453 Laminaria Species 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 1
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 1
- PNUCWVAGVNLUMW-CIUDSAMLSA-N Leu-Cys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O PNUCWVAGVNLUMW-CIUDSAMLSA-N 0.000 description 1
- QVFGXCVIXXBFHO-AVGNSLFASA-N Leu-Glu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O QVFGXCVIXXBFHO-AVGNSLFASA-N 0.000 description 1
- VZBIUJURDLFFOE-IHRRRGAJSA-N Leu-His-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VZBIUJURDLFFOE-IHRRRGAJSA-N 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 1
- UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 description 1
- MUCIDQMDOYQYBR-IHRRRGAJSA-N Leu-Pro-His Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N MUCIDQMDOYQYBR-IHRRRGAJSA-N 0.000 description 1
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 1
- SQUFDMCWMFOEBA-KKUMJFAQSA-N Leu-Ser-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 SQUFDMCWMFOEBA-KKUMJFAQSA-N 0.000 description 1
- ONHCDMBHPQIPAI-YTQUADARSA-N Leu-Trp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N3CCC[C@@H]3C(=O)O)N ONHCDMBHPQIPAI-YTQUADARSA-N 0.000 description 1
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 1
- MSFITIBEMPWCBD-ULQDDVLXSA-N Leu-Val-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 MSFITIBEMPWCBD-ULQDDVLXSA-N 0.000 description 1
- 206010057180 Liver and spleen enlargement Diseases 0.000 description 1
- MRWXLRGAFDOILG-DCAQKATOSA-N Lys-Gln-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MRWXLRGAFDOILG-DCAQKATOSA-N 0.000 description 1
- ITWQLSZTLBKWJM-YUMQZZPRSA-N Lys-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCCN ITWQLSZTLBKWJM-YUMQZZPRSA-N 0.000 description 1
- ALEVUGKHINJNIF-QEJZJMRPSA-N Lys-Phe-Ala Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 ALEVUGKHINJNIF-QEJZJMRPSA-N 0.000 description 1
- BVRNWWHJYNPJDG-XIRDDKMYSA-N Lys-Trp-Asn Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N BVRNWWHJYNPJDG-XIRDDKMYSA-N 0.000 description 1
- IKXQOBUBZSOWDY-AVGNSLFASA-N Lys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N IKXQOBUBZSOWDY-AVGNSLFASA-N 0.000 description 1
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 description 1
- 208000015439 Lysosomal storage disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- ZAJNRWKGHWGPDQ-SDDRHHMPSA-N Met-Arg-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N ZAJNRWKGHWGPDQ-SDDRHHMPSA-N 0.000 description 1
- 206010027727 Mitral valve incompetence Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 description 1
- 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 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030124 Oedema peripheral Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- LSXGADJXBDFXQU-DLOVCJGASA-N Phe-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 LSXGADJXBDFXQU-DLOVCJGASA-N 0.000 description 1
- AJOKKVTWEMXZHC-DRZSPHRISA-N Phe-Ala-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 AJOKKVTWEMXZHC-DRZSPHRISA-N 0.000 description 1
- MECSIDWUTYRHRJ-KKUMJFAQSA-N Phe-Asn-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O MECSIDWUTYRHRJ-KKUMJFAQSA-N 0.000 description 1
- WMGVYPPIMZPWPN-SRVKXCTJSA-N Phe-Asp-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N WMGVYPPIMZPWPN-SRVKXCTJSA-N 0.000 description 1
- YCCUXNNKXDGMAM-KKUMJFAQSA-N Phe-Leu-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YCCUXNNKXDGMAM-KKUMJFAQSA-N 0.000 description 1
- MGLBSROLWAWCKN-FCLVOEFKSA-N Phe-Phe-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MGLBSROLWAWCKN-FCLVOEFKSA-N 0.000 description 1
- ODGNUUUDJONJSC-UFYCRDLUSA-N Phe-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O ODGNUUUDJONJSC-UFYCRDLUSA-N 0.000 description 1
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 1
- CXMSESHALPOLRE-MEYUZBJRSA-N Phe-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N)O CXMSESHALPOLRE-MEYUZBJRSA-N 0.000 description 1
- VDTYRPWRWRCROL-UFYCRDLUSA-N Phe-Val-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 VDTYRPWRWRCROL-UFYCRDLUSA-N 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- KIZQGKLMXKGDIV-BQBZGAKWSA-N Pro-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 KIZQGKLMXKGDIV-BQBZGAKWSA-N 0.000 description 1
- SGCZFWSQERRKBD-BQBZGAKWSA-N Pro-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 SGCZFWSQERRKBD-BQBZGAKWSA-N 0.000 description 1
- ZPPVJIJMIKTERM-YUMQZZPRSA-N Pro-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ZPPVJIJMIKTERM-YUMQZZPRSA-N 0.000 description 1
- SKICPQLTOXGWGO-GARJFASQSA-N Pro-Gln-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)N)C(=O)N2CCC[C@@H]2C(=O)O SKICPQLTOXGWGO-GARJFASQSA-N 0.000 description 1
- LCUOTSLIVGSGAU-AVGNSLFASA-N Pro-His-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LCUOTSLIVGSGAU-AVGNSLFASA-N 0.000 description 1
- YTWNSIDWAFSEEI-RWMBFGLXSA-N Pro-His-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@@H]3C(=O)O YTWNSIDWAFSEEI-RWMBFGLXSA-N 0.000 description 1
- AQSMZTIEJMZQEC-DCAQKATOSA-N Pro-His-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CO)C(=O)O AQSMZTIEJMZQEC-DCAQKATOSA-N 0.000 description 1
- LPGSNRSLPHRNBW-AVGNSLFASA-N Pro-His-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C([O-])=O)NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 LPGSNRSLPHRNBW-AVGNSLFASA-N 0.000 description 1
- MCWHYUWXVNRXFV-RWMBFGLXSA-N Pro-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 MCWHYUWXVNRXFV-RWMBFGLXSA-N 0.000 description 1
- SUENWIFTSTWUKD-AVGNSLFASA-N Pro-Leu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O SUENWIFTSTWUKD-AVGNSLFASA-N 0.000 description 1
- SVXXJYJCRNKDDE-AVGNSLFASA-N Pro-Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NCCC1)C1=CN=CN1 SVXXJYJCRNKDDE-AVGNSLFASA-N 0.000 description 1
- CGSOWZUPLOKYOR-AVGNSLFASA-N Pro-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 CGSOWZUPLOKYOR-AVGNSLFASA-N 0.000 description 1
- KWMZPPWYBVZIER-XGEHTFHBSA-N Pro-Ser-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWMZPPWYBVZIER-XGEHTFHBSA-N 0.000 description 1
- FIODMZKLZFLYQP-GUBZILKMSA-N Pro-Val-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FIODMZKLZFLYQP-GUBZILKMSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 206010067171 Regurgitation Diseases 0.000 description 1
- QFBNNYNWKYKVJO-DCAQKATOSA-N Ser-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N QFBNNYNWKYKVJO-DCAQKATOSA-N 0.000 description 1
- CRZRTKAVUUGKEQ-ACZMJKKPSA-N Ser-Gln-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CRZRTKAVUUGKEQ-ACZMJKKPSA-N 0.000 description 1
- RIAKPZVSNBBNRE-BJDJZHNGSA-N Ser-Ile-Leu Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O RIAKPZVSNBBNRE-BJDJZHNGSA-N 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 1
- LPSKHZWBQONOQJ-XIRDDKMYSA-N Ser-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N LPSKHZWBQONOQJ-XIRDDKMYSA-N 0.000 description 1
- JCLAFVNDBJMLBC-JBDRJPRFSA-N Ser-Ser-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JCLAFVNDBJMLBC-JBDRJPRFSA-N 0.000 description 1
- PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 1
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 1
- FGBLCMLXHRPVOF-IHRRRGAJSA-N Ser-Tyr-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FGBLCMLXHRPVOF-IHRRRGAJSA-N 0.000 description 1
- PQEQXWRVHQAAKS-SRVKXCTJSA-N Ser-Tyr-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)N)CC1=CC=C(O)C=C1 PQEQXWRVHQAAKS-SRVKXCTJSA-N 0.000 description 1
- HXPNJVLVHKABMJ-KKUMJFAQSA-N Ser-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CO)N)O HXPNJVLVHKABMJ-KKUMJFAQSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- MQCPGOZXFSYJPS-KZVJFYERSA-N Thr-Ala-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MQCPGOZXFSYJPS-KZVJFYERSA-N 0.000 description 1
- TWLMXDWFVNEFFK-FJXKBIBVSA-N Thr-Arg-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O TWLMXDWFVNEFFK-FJXKBIBVSA-N 0.000 description 1
- GZYNMZQXFRWDFH-YTWAJWBKSA-N Thr-Arg-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O GZYNMZQXFRWDFH-YTWAJWBKSA-N 0.000 description 1
- JBHMLZSKIXMVFS-XVSYOHENSA-N Thr-Asn-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JBHMLZSKIXMVFS-XVSYOHENSA-N 0.000 description 1
- SLUWOCTZVGMURC-BFHQHQDPSA-N Thr-Gly-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O SLUWOCTZVGMURC-BFHQHQDPSA-N 0.000 description 1
- ZTPXSEUVYNNZRB-CDMKHQONSA-N Thr-Gly-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZTPXSEUVYNNZRB-CDMKHQONSA-N 0.000 description 1
- NCGUQWSJUKYCIT-SZZJOZGLSA-N Thr-His-Trp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O NCGUQWSJUKYCIT-SZZJOZGLSA-N 0.000 description 1
- AMXMBCAXAZUCFA-RHYQMDGZSA-N Thr-Leu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMXMBCAXAZUCFA-RHYQMDGZSA-N 0.000 description 1
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 1
- VTMGKRABARCZAX-OSUNSFLBSA-N Thr-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O VTMGKRABARCZAX-OSUNSFLBSA-N 0.000 description 1
- YGCDFAJJCRVQKU-RCWTZXSCSA-N Thr-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O YGCDFAJJCRVQKU-RCWTZXSCSA-N 0.000 description 1
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 1
- QYDKSNXSBXZPFK-ZJDVBMNYSA-N Thr-Thr-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYDKSNXSBXZPFK-ZJDVBMNYSA-N 0.000 description 1
- ZMYCLHFLHRVOEA-HEIBUPTGSA-N Thr-Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ZMYCLHFLHRVOEA-HEIBUPTGSA-N 0.000 description 1
- BJJRNAVDQGREGC-HOUAVDHOSA-N Thr-Trp-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O BJJRNAVDQGREGC-HOUAVDHOSA-N 0.000 description 1
- 201000001943 Tricuspid Valve Insufficiency Diseases 0.000 description 1
- 206010044640 Tricuspid valve incompetence Diseases 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- KRCPXGSWDOGHAM-XIRDDKMYSA-N Trp-Lys-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O KRCPXGSWDOGHAM-XIRDDKMYSA-N 0.000 description 1
- XOLLWQIBBLBAHQ-WDSOQIARSA-N Trp-Pro-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O XOLLWQIBBLBAHQ-WDSOQIARSA-N 0.000 description 1
- BOBZBMOTRORUPT-XIRDDKMYSA-N Trp-Ser-Leu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O)=CNC2=C1 BOBZBMOTRORUPT-XIRDDKMYSA-N 0.000 description 1
- VCXWRWYFJLXITF-AUTRQRHGSA-N Tyr-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VCXWRWYFJLXITF-AUTRQRHGSA-N 0.000 description 1
- TVOGEPLDNYTAHD-CQDKDKBSSA-N Tyr-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TVOGEPLDNYTAHD-CQDKDKBSSA-N 0.000 description 1
- OEVJGIHPQOXYFE-SRVKXCTJSA-N Tyr-Asn-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O OEVJGIHPQOXYFE-SRVKXCTJSA-N 0.000 description 1
- KCPFDGNYAMKZQP-KBPBESRZSA-N Tyr-Gly-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O KCPFDGNYAMKZQP-KBPBESRZSA-N 0.000 description 1
- STTVVMWQKDOKAM-YESZJQIVSA-N Tyr-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O STTVVMWQKDOKAM-YESZJQIVSA-N 0.000 description 1
- QARCDOCCDOLJSF-HJPIBITLSA-N Tyr-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QARCDOCCDOLJSF-HJPIBITLSA-N 0.000 description 1
- ABSXSJZNRAQDDI-KJEVXHAQSA-N Tyr-Val-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ABSXSJZNRAQDDI-KJEVXHAQSA-N 0.000 description 1
- IZFVRRYRMQFVGX-NRPADANISA-N Val-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N IZFVRRYRMQFVGX-NRPADANISA-N 0.000 description 1
- VDPRBUOZLIFUIM-GUBZILKMSA-N Val-Arg-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N VDPRBUOZLIFUIM-GUBZILKMSA-N 0.000 description 1
- DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 1
- BYOHPUZJVXWHAE-BYULHYEWSA-N Val-Asn-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N BYOHPUZJVXWHAE-BYULHYEWSA-N 0.000 description 1
- ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 1
- VFOHXOLPLACADK-GVXVVHGQSA-N Val-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N VFOHXOLPLACADK-GVXVVHGQSA-N 0.000 description 1
- JVYIGCARISMLMV-HOCLYGCPSA-N Val-Gly-Trp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N JVYIGCARISMLMV-HOCLYGCPSA-N 0.000 description 1
- XBRMBDFYOFARST-AVGNSLFASA-N Val-His-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N XBRMBDFYOFARST-AVGNSLFASA-N 0.000 description 1
- YLRAFVVWZRSZQC-DZKIICNBSA-N Val-Phe-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N YLRAFVVWZRSZQC-DZKIICNBSA-N 0.000 description 1
- KISFXYYRKKNLOP-IHRRRGAJSA-N Val-Phe-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)O)N KISFXYYRKKNLOP-IHRRRGAJSA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- DLLRRUDLMSJTMB-GUBZILKMSA-N Val-Ser-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)O)N DLLRRUDLMSJTMB-GUBZILKMSA-N 0.000 description 1
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- YLBNZCJFSVJDRJ-KJEVXHAQSA-N Val-Thr-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O YLBNZCJFSVJDRJ-KJEVXHAQSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 108010041407 alanylaspartic acid Proteins 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 108010060162 alglucerase Proteins 0.000 description 1
- 229960003122 alglucerase Drugs 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000012539 chromatography resin Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011513 continuous positive airway pressure therapy Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 108010060199 cysteinylproline Proteins 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940079919 digestives enzyme preparation Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 108010085325 histidylproline Proteins 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
- 208000024326 hypersensitivity reaction type III disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002703 mannose derivatives Chemical class 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 101150091879 neo gene Proteins 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 108010012581 phenylalanylglutamate Proteins 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 208000024335 physical disease Diseases 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009101 premedication Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 108010079317 prolyl-tyrosine Proteins 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 108010090894 prolylleucine Proteins 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000009613 pulmonary function test Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 230000003860 sleep quality Effects 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 1
- 238000013060 ultrafiltration and diafiltration Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 108010009962 valyltyrosine Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01014—Chitinase (3.2.1.14)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01075—Glucan endo-1,6-beta-glucosidase (3.2.1.75)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01076—L-Iduronidase (3.2.1.76)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y402/00—Carbon-oxygen lyases (4.2)
- C12Y402/02—Carbon-oxygen lyases (4.2) acting on polysaccharides (4.2.2)
- C12Y402/02004—Chondroitin ABC lyase (4.2.2.4), i.e. chondroitinase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/439,923 US6426208B1 (en) | 1999-11-12 | 1999-11-12 | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
| US09439,923 | 1999-11-12 | ||
| PCT/US2000/031293 WO2002004616A1 (en) | 1999-11-12 | 2000-11-09 | RECOMBINANT α-L-IDURONIDASE, METHODS FOR PRODUCING AND PURIFYING THE SAME AND METHODS FOR TREATING DISEASES CAUSED BY DEFICIENCIES THEREOF |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2391098A1 CA2391098A1 (en) | 2002-01-17 |
| CA2391098C true CA2391098C (en) | 2007-10-23 |
Family
ID=23746702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002391098A Expired - Lifetime CA2391098C (en) | 1999-11-12 | 2000-11-09 | Recombinant .alpha.-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US6426208B1 (enExample) |
| EP (2) | EP1792983B1 (enExample) |
| JP (3) | JP2004502456A (enExample) |
| CN (2) | CN101407796A (enExample) |
| AT (2) | ATE430193T1 (enExample) |
| AU (2) | AU773663B2 (enExample) |
| BR (1) | BRPI0015533B8 (enExample) |
| CA (1) | CA2391098C (enExample) |
| DE (2) | DE60042137D1 (enExample) |
| ES (2) | ES2273748T3 (enExample) |
| IL (3) | IL149568A0 (enExample) |
| MX (1) | MXPA02004742A (enExample) |
| WO (1) | WO2002004616A1 (enExample) |
| ZA (1) | ZA200203619B (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6585971B1 (en) * | 1999-11-12 | 2003-07-01 | Harbor-Ucla Research And Education Institute | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating disease caused by deficiencies thereof |
| US6569661B1 (en) * | 1999-11-12 | 2003-05-27 | Biomarin Pharmaceutical Inc. | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
| JP2004522763A (ja) * | 2001-02-20 | 2004-07-29 | ユーエイビー リサーチ ファンデーション | リソソーム蓄積症のアミノグリコシド治療 |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US7629309B2 (en) | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US7485314B2 (en) * | 2002-05-06 | 2009-02-03 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Induction of antigen specific immunologic tolerance |
| US20050026823A1 (en) | 2003-06-20 | 2005-02-03 | Biomarin Pharmaceutical Inc. | Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues |
| CA2535816A1 (en) * | 2003-08-21 | 2005-03-10 | Q Therapeutics, Inc. | Genetically modified somatic cells for sustained secretion of lysosomal proenzymes deficient in lysosomal storage disorders |
| US7442372B2 (en) * | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| MXPA03011987A (es) | 2003-12-19 | 2005-06-23 | Osio Sancho Alberto | Metodo para el tratamiento de la presbicia induciendo cambios en el poder y fisiologia corneal. |
| US9062126B2 (en) | 2005-09-16 | 2015-06-23 | Raptor Pharmaceuticals Inc. | Compositions comprising receptor-associated protein (RAP) variants specific for CR-containing proteins and uses thereof |
| WO2007065273A1 (en) * | 2005-12-08 | 2007-06-14 | The University Of British Columbia | Mucopolysaccharidosis (mps) diagnostic methods, systems, kits and assays associated therewith |
| EP2132224B1 (en) * | 2007-03-21 | 2011-12-28 | Raptor Pharmaceutical Inc | Cyclic receptor-associated protein (rap) peptides |
| PL3327026T3 (pl) | 2007-07-09 | 2020-02-28 | Genentech, Inc. | Zapobieganie redukcji wiązań disiarczkowych podczas rekombinacyjnego wytwarzania polipeptydów |
| ES2387251T3 (es) * | 2008-02-21 | 2012-09-19 | Fiat Group Automobiles S.P.A. | Conjunto de soporte de vidrio para una puerta de vehículo a motor con un borde superior sin armazón |
| HUE034850T2 (en) | 2008-05-07 | 2018-03-28 | Biomarin Pharm Inc | Lysosomal targeting peptides and their use |
| EP3679942A1 (en) | 2009-06-17 | 2020-07-15 | BioMarin Pharmaceutical Inc. | Formulations for lysosomal enzymes |
| WO2012101671A1 (en) * | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
| DE102011102170B4 (de) | 2011-05-20 | 2024-06-06 | Vitesco Technologies GmbH | Einspritzvorrichtung zur Einspritzung eines Fluids |
| HK1209633A1 (en) | 2012-06-19 | 2016-04-08 | University Of Florida Research Foundation, Inc. | Compositions and methods for treating diabetes |
| IN2015KN00596A (enExample) | 2012-08-10 | 2015-07-17 | Osio Corp D B A Yolia Health | |
| MX386059B (es) * | 2013-03-15 | 2025-03-18 | Univ Pennsylvania | COMPOSICIONES Y SUS usos EN EL TRATAMIENTO DE LA MUCOPOLISACARIDOSIS TIPO I. |
| IL260959B2 (en) | 2016-02-03 | 2024-09-01 | Univ Pennsylvania | Gene therapy for treating mucopolysaccharidosis type i |
| WO2018144441A1 (en) * | 2017-01-31 | 2018-08-09 | Regenxbio Inc. | Treatment of mucopolysaccharidosis i with fully-human glycosylated human alpha-l-iduronidase (idua) |
| BR112020000063A2 (pt) | 2017-07-06 | 2020-07-14 | The Trustees Of The University Of Pennsylvania | terapia gênica mediada por aav9 para tratamento de mucopolissacaridose tipo i |
| AU2018335752B2 (en) | 2017-09-22 | 2025-04-10 | Christian HINDERER | Gene therapy for treating Mucopolysaccharidosis type ii |
| CN107699590A (zh) * | 2017-10-13 | 2018-02-16 | 成都中医药大学 | 一种制备重组人α‑L‑艾杜糖醛酸酶的方法 |
| WO2020132100A1 (en) | 2018-12-19 | 2020-06-25 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules for lysosomal targeting and related compositions and methods |
| CN110577559B (zh) * | 2019-08-19 | 2023-02-17 | 江西科技师范大学 | α-L-艾杜糖醛酸酶测定用荧光糖苷酶底物的合成方法 |
| WO2022145449A1 (ja) * | 2021-01-04 | 2022-07-07 | 国立大学法人徳島大学 | ライソゾームを標的とした新規ddsの開発 |
| JP2022105471A (ja) * | 2021-01-04 | 2022-07-14 | 国立大学法人徳島大学 | ライソゾームを標的とした新規ddsの開発 |
| CN115109790A (zh) * | 2021-03-23 | 2022-09-27 | 北京据德医药科技有限公司 | 一种重组a-L-艾杜糖醛酸普酶及其制备方法 |
| WO2023288033A1 (en) | 2021-07-14 | 2023-01-19 | Lycia Therapeutics, Inc. | Asgpr cell surface receptor binding compounds and conjugates |
| CN114181318B (zh) * | 2021-11-08 | 2023-08-01 | 四川大学 | 一种组织特异性表达穿透血脑屏障的idua融合蛋白的重组腺相关病毒及应用 |
| CN115161284B (zh) * | 2022-07-04 | 2024-07-09 | 无锡多宁生物科技有限公司 | 一种lmh悬浮细胞复苏培养方法及其应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL281225A (enExample) | 1961-07-20 | |||
| GB1029548A (en) | 1963-07-17 | 1966-05-11 | Amagasaki Iron & Steel Mfg Co | Corrugated roofing sheet |
| US3472931A (en) | 1969-01-17 | 1969-10-14 | Foster Milburn Co | Percutaneous absorption with lower alkyl amides |
| US3891757A (en) | 1971-11-11 | 1975-06-24 | Alza Corp | Anaesthetic topical and percutaneous administration with selected promoters |
| US5270051A (en) | 1991-10-15 | 1993-12-14 | Harris Donald H | Enzyme-orthokeratology |
| US6149909A (en) * | 1995-06-23 | 2000-11-21 | Women's And Children's Hospital | Synthetic α-L-iduronidase and genetic sequences encoding same |
| AU649897B2 (en) | 1991-11-14 | 1994-06-02 | Women's And Children's Hospital | Synthetic alpha-L-iduronidase and genetic sequences encoding same |
| US5278051A (en) * | 1991-12-12 | 1994-01-11 | New York University | Construction of geometrical objects from polynucleotides |
| ATE426031T1 (de) | 1995-09-14 | 2009-04-15 | Virginia Tech Intell Prop | Produktion von lysosomalen enzymen in pflanzlichen expressionssystemen |
| GB9807464D0 (en) | 1998-04-07 | 1998-06-10 | Pharming Bv | Purification of human acid µ-glucosidase |
| IL139616A0 (en) | 1998-05-13 | 2002-02-10 | Harbor Ucla | Recombinant (alpha)-l-iduronidase, methods for producing and purifying the same and methods for treating, diseases caused by deficiencies thereof |
-
1999
- 1999-11-12 US US09/439,923 patent/US6426208B1/en not_active Expired - Lifetime
-
2000
- 2000-11-09 WO PCT/US2000/031293 patent/WO2002004616A1/en not_active Ceased
- 2000-11-09 AU AU84635/01A patent/AU773663B2/en not_active Expired
- 2000-11-09 CN CNA2008101440588A patent/CN101407796A/zh active Pending
- 2000-11-09 DE DE60042137T patent/DE60042137D1/de not_active Expired - Lifetime
- 2000-11-09 CN CN008181705A patent/CN1420924B/zh not_active Expired - Lifetime
- 2000-11-09 EP EP06011595A patent/EP1792983B1/en not_active Expired - Lifetime
- 2000-11-09 JP JP2002509470A patent/JP2004502456A/ja not_active Withdrawn
- 2000-11-09 EP EP00993857A patent/EP1332206B1/en not_active Expired - Lifetime
- 2000-11-09 ES ES00993857T patent/ES2273748T3/es not_active Expired - Lifetime
- 2000-11-09 BR BRPI0015533A patent/BRPI0015533B8/pt not_active IP Right Cessation
- 2000-11-09 IL IL14956800A patent/IL149568A0/xx unknown
- 2000-11-09 AT AT06011595T patent/ATE430193T1/de not_active IP Right Cessation
- 2000-11-09 DE DE60031456T patent/DE60031456T2/de not_active Expired - Lifetime
- 2000-11-09 AT AT00993857T patent/ATE342964T1/de not_active IP Right Cessation
- 2000-11-09 ES ES06011595T patent/ES2324727T3/es not_active Expired - Lifetime
- 2000-11-09 CA CA002391098A patent/CA2391098C/en not_active Expired - Lifetime
- 2000-11-09 MX MXPA02004742A patent/MXPA02004742A/es active IP Right Grant
-
2002
- 2002-05-07 ZA ZA200203619A patent/ZA200203619B/en unknown
- 2002-05-09 IL IL149568A patent/IL149568A/en active IP Right Grant
- 2002-07-25 US US10/206,443 patent/US7041487B2/en not_active Expired - Lifetime
-
2004
- 2004-08-23 JP JP2004242343A patent/JP3857705B2/ja not_active Expired - Lifetime
- 2004-09-03 AU AU2004208651A patent/AU2004208651A1/en not_active Abandoned
-
2006
- 2006-05-05 US US11/429,422 patent/US20060286087A1/en not_active Abandoned
- 2006-08-07 JP JP2006215076A patent/JP2006312648A/ja active Pending
-
2008
- 2008-06-11 IL IL192078A patent/IL192078A/en active IP Right Grant
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2391098C (en) | Recombinant .alpha.-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof | |
| US6585971B1 (en) | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating disease caused by deficiencies thereof | |
| US6569661B1 (en) | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof | |
| RU2766680C1 (ru) | Новые варианты гиалуронидазы и содержащая их фармацевтическая композиция | |
| US20020127652A1 (en) | Follicle stimulating hormones | |
| US20030036181A1 (en) | Peptide extended glycosylated polypeptides | |
| CA2825163C (en) | Compositions for regulating iron homeostasis and methods of using same | |
| KR101522217B1 (ko) | Fsh 제조 세포 클론 | |
| KR20140128453A (ko) | 이상혈색소증 치료를 위한 조성물 및 방법 | |
| CA2328518A1 (en) | Recombinant (alpha)-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof | |
| BR9712767B1 (pt) | sequência de ácidos nucléicos codificando um polipeptìdio de fusão bem como vetor compreendendo a dita sequência. | |
| EP0607247A1 (en) | Production of gpa neurotrophic factor | |
| MXPA00011137A (en) | Recombinant (alpha)-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof | |
| CN104862336B (zh) | 一种表达乙肝病毒受体——人ntcp的小鼠模型的构建方法 | |
| EP0870036A1 (en) | SYNTHETIC MAMMALIAN $g(a)-N-ACETYLGLUCOSAMINIDASE AND GENETIC SEQUENCES ENCODING SAME | |
| CN107287240B (zh) | 一种用于治疗2型全色盲病人的重组腺相关病毒基因治疗载体及药物 | |
| CN102051378A (zh) | 以病毒mRNA核转运为靶点的抗HIV-1药物筛选方法 | |
| US20060040348A1 (en) | Methods for producing and purifying recombinant alpha-L-iduronidase | |
| HK1104836B (en) | Recombinant alpha-l-iduronidase and methods for treating diseases caused by deficiencies thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20201109 |