CA2551131A1 - Novel recombinant proteins with n-terminal free thiol - Google Patents
Novel recombinant proteins with n-terminal free thiol Download PDFInfo
- Publication number
- CA2551131A1 CA2551131A1 CA002551131A CA2551131A CA2551131A1 CA 2551131 A1 CA2551131 A1 CA 2551131A1 CA 002551131 A CA002551131 A CA 002551131A CA 2551131 A CA2551131 A CA 2551131A CA 2551131 A1 CA2551131 A1 CA 2551131A1
- Authority
- CA
- Canada
- Prior art keywords
- epo
- moiety
- conjugate
- erythropoietin
- erythropoietic
- 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.)
- Abandoned
Links
- 125000003396 thiol group Chemical class [H]S* 0.000 title abstract description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 title description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 title description 3
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims abstract description 140
- 108090000394 Erythropoietin Proteins 0.000 claims abstract description 130
- 102000003951 Erythropoietin Human genes 0.000 claims abstract description 129
- 229940105423 erythropoietin Drugs 0.000 claims abstract description 127
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 106
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 98
- 235000018102 proteins Nutrition 0.000 claims abstract description 97
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims abstract description 44
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 38
- 150000003573 thiols Chemical class 0.000 claims abstract description 37
- 235000018417 cysteine Nutrition 0.000 claims abstract description 35
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims abstract description 34
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 32
- 150000001413 amino acids Chemical class 0.000 claims abstract description 27
- 229920000642 polymer Polymers 0.000 claims abstract description 27
- 235000001014 amino acid Nutrition 0.000 claims abstract description 25
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 210000003743 erythrocyte Anatomy 0.000 claims abstract description 13
- 230000004071 biological effect Effects 0.000 claims abstract description 12
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 claims abstract description 11
- 102000044890 human EPO Human genes 0.000 claims abstract description 11
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 8
- 210000002798 bone marrow cell Anatomy 0.000 claims abstract description 7
- 108010092408 Eosinophil Peroxidase Proteins 0.000 claims abstract 6
- 102100031939 Erythropoietin Human genes 0.000 claims abstract 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 68
- 239000002202 Polyethylene glycol Substances 0.000 claims description 49
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 43
- 210000004027 cell Anatomy 0.000 claims description 43
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 31
- 229930195729 fatty acid Natural products 0.000 claims description 31
- 239000000194 fatty acid Substances 0.000 claims description 31
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 29
- 229920001184 polypeptide Polymers 0.000 claims description 23
- 230000000913 erythropoietic effect Effects 0.000 claims description 22
- 230000001225 therapeutic effect Effects 0.000 claims description 19
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 13
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims description 13
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 150000002148 esters Chemical group 0.000 claims description 9
- 150000003457 sulfones Chemical class 0.000 claims description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 239000007795 chemical reaction product Substances 0.000 claims description 8
- 150000007523 nucleic acids Chemical group 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- MBDUIEKYVPVZJH-UHFFFAOYSA-N 1-ethylsulfonylethane Chemical compound CCS(=O)(=O)CC MBDUIEKYVPVZJH-UHFFFAOYSA-N 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 6
- 208000007502 anemia Diseases 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 150000003904 phospholipids Chemical class 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 6
- 150000007970 thio esters Chemical class 0.000 claims description 6
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 5
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 5
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 5
- 239000000854 Human Growth Hormone Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000005313 fatty acid group Chemical group 0.000 claims description 5
- 238000011160 research Methods 0.000 claims description 5
- 102000014150 Interferons Human genes 0.000 claims description 4
- 108010050904 Interferons Proteins 0.000 claims description 4
- 229960002685 biotin Drugs 0.000 claims description 4
- 235000020958 biotin Nutrition 0.000 claims description 4
- 239000011616 biotin Substances 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 238000002741 site-directed mutagenesis Methods 0.000 claims description 4
- 108020004705 Codon Proteins 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 230000001268 conjugating effect Effects 0.000 claims description 3
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 238000011144 upstream manufacturing Methods 0.000 claims description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 125000000837 carbohydrate group Chemical group 0.000 claims description 2
- 230000002255 enzymatic effect Effects 0.000 claims description 2
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000003827 glycol group Chemical group 0.000 claims 5
- 229920001519 homopolymer Polymers 0.000 claims 3
- 125000003473 lipid group Chemical group 0.000 claims 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- 230000002459 sustained effect Effects 0.000 claims 2
- 229920001400 block copolymer Polymers 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 claims 1
- 229920001451 polypropylene glycol Polymers 0.000 claims 1
- 230000012846 protein folding Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 10
- 238000001212 derivatisation Methods 0.000 abstract description 4
- 102000035118 modified proteins Human genes 0.000 abstract description 4
- 108091005573 modified proteins Proteins 0.000 abstract description 4
- 229920001515 polyalkylene glycol Polymers 0.000 abstract description 2
- 238000010188 recombinant method Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 28
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 24
- -1 fatty acid ester Chemical class 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 19
- 239000000047 product Substances 0.000 description 18
- 150000004665 fatty acids Chemical class 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000003776 cleavage reaction Methods 0.000 description 14
- 239000002953 phosphate buffered saline Substances 0.000 description 14
- 230000007017 scission Effects 0.000 description 14
- 150000001720 carbohydrates Chemical class 0.000 description 13
- 235000014633 carbohydrates Nutrition 0.000 description 12
- 239000002243 precursor Substances 0.000 description 12
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 230000000975 bioactive effect Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000021615 conjugation Effects 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 125000003275 alpha amino acid group Chemical group 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000005534 hematocrit Methods 0.000 description 7
- 230000000926 neurological effect Effects 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000013595 glycosylation Effects 0.000 description 6
- 238000006206 glycosylation reaction Methods 0.000 description 6
- 125000005647 linker group Chemical group 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 230000006320 pegylation Effects 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 5
- 108090000288 Glycoproteins Proteins 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 208000020431 spinal cord injury Diseases 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 238000000672 surface-enhanced laser desorption--ionisation Methods 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000007385 chemical modification Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- 208000019838 Blood disease Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 208000017442 Retinal disease Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 208000029028 brain injury Diseases 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 150000001991 dicarboxylic acids Chemical class 0.000 description 3
- 150000002019 disulfides Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002191 fatty alcohols Chemical class 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 208000014951 hematologic disease Diseases 0.000 description 3
- 208000018706 hematopoietic system disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- XSYUPRQVAHJETO-WPMUBMLPSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidaz Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 XSYUPRQVAHJETO-WPMUBMLPSA-N 0.000 description 2
- LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 241001244729 Apalis Species 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 108010019673 Darbepoetin alfa Proteins 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 101150002621 EPO gene Proteins 0.000 description 2
- 102100032610 Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas Human genes 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- HPEUJPJOZXNMSJ-UHFFFAOYSA-N Methyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC HPEUJPJOZXNMSJ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- UWHCKJMYHZGTIT-UHFFFAOYSA-N Tetraethylene glycol, Natural products OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 239000004927 clay Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- DGXRZJSPDXZJFG-UHFFFAOYSA-N docosanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCCCCCC(O)=O DGXRZJSPDXZJFG-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940048820 edetates Drugs 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- MVLVMROFTAUDAG-UHFFFAOYSA-N ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC MVLVMROFTAUDAG-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 230000008816 organ damage Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000009145 protein modification Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 150000004671 saturated fatty acids Chemical class 0.000 description 2
- 235000003441 saturated fatty acids Nutrition 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 125000001174 sulfone group Chemical group 0.000 description 2
- 238000011477 surgical intervention Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- HQHCYKULIHKCEB-UHFFFAOYSA-N tetradecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCC(O)=O HQHCYKULIHKCEB-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LUYAMNYBNTVQJG-UHFFFAOYSA-N 1-chloro-2-(2-chloroethylsulfonyl)ethane Chemical compound ClCCS(=O)(=O)CCCl LUYAMNYBNTVQJG-UHFFFAOYSA-N 0.000 description 1
- XGMDYIYCKWMWLY-UHFFFAOYSA-N 2,2,2-trifluoroethanesulfonic acid Chemical compound OS(=O)(=O)CC(F)(F)F XGMDYIYCKWMWLY-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 206010002068 Anaemia neonatal Diseases 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- NDKYEUQMPZIGFN-UHFFFAOYSA-N Butyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCC NDKYEUQMPZIGFN-UHFFFAOYSA-N 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241001660259 Cereus <cactus> Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 206010061452 Complication of pregnancy Diseases 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100024099 Disks large homolog 1 Human genes 0.000 description 1
- 108010074604 Epoetin Alfa Proteins 0.000 description 1
- 108010075944 Erythropoietin Receptors Proteins 0.000 description 1
- 102100036509 Erythropoietin receptor Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 102100029880 Glycodelin Human genes 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 1
- 101001053984 Homo sapiens Disks large homolog 1 Proteins 0.000 description 1
- 101100333654 Homo sapiens EPO gene Proteins 0.000 description 1
- 101000585553 Homo sapiens Glycodelin Proteins 0.000 description 1
- 101000693243 Homo sapiens Paternally-expressed gene 3 protein Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 1
- 101710184243 Intestinal-type alkaline phosphatase Proteins 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 108010036940 Levansucrase Proteins 0.000 description 1
- 208000019255 Menstrual disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical group CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010058116 Nephrogenic anaemia Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- QIPQASLPWJVQMH-DTORHVGOSA-N Orbifloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(F)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F QIPQASLPWJVQMH-DTORHVGOSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 102100025757 Paternally-expressed gene 3 protein Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920002266 Pluriol® Polymers 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000677647 Proba Species 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 241000193803 Therea Species 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000012436 analytical size exclusion chromatography Methods 0.000 description 1
- 201000000975 anemia of prematurity Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940114078 arachidonate Drugs 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003323 beak Anatomy 0.000 description 1
- 229940116224 behenate Drugs 0.000 description 1
- UKMSUNONTOPOIO-UHFFFAOYSA-M behenate Chemical compound CCCCCCCCCCCCCCCCCCCCCC([O-])=O UKMSUNONTOPOIO-UHFFFAOYSA-M 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 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 description 1
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940089118 epogen Drugs 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- JIFCVUWJQMDNTN-UHFFFAOYSA-N hexyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCCCC JIFCVUWJQMDNTN-UHFFFAOYSA-N 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- VQEUONXRKIUTJT-UHFFFAOYSA-N lauric acid sec-butyl ester Natural products CCCCCCCCCCCC(=O)OC(C)CC VQEUONXRKIUTJT-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003039 myelosuppressive effect Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000003924 normoblast Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940001566 orbax Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000000063 preceeding effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 208000012113 pregnancy disease Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BTAXGNQLYFDKEF-UHFFFAOYSA-N propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCC BTAXGNQLYFDKEF-UHFFFAOYSA-N 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000020874 response to hypoxia Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220147056 rs150475750 Human genes 0.000 description 1
- 102200006515 rs727503110 Human genes 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001920 surface-enhanced laser desorption--ionisation mass spectrometry Methods 0.000 description 1
- JDMUZPCDCYZTJA-UHFFFAOYSA-N tert-butyl 2,2-diaminoheptanoate Chemical compound CCCCCC(N)(N)C(=O)OC(C)(C)C JDMUZPCDCYZTJA-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CWXZMNMLGZGDSW-UHFFFAOYSA-N tetracontanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)=O CWXZMNMLGZGDSW-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- VHOCUJPBKOZGJD-UHFFFAOYSA-N triacontanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)=O VHOCUJPBKOZGJD-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- CMPGARWFYBADJI-UHFFFAOYSA-L tungstic acid Chemical compound O[W](O)(=O)=O CMPGARWFYBADJI-UHFFFAOYSA-L 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53361703P | 2003-12-31 | 2003-12-31 | |
| US60/533,617 | 2003-12-31 | ||
| PCT/US2004/043081 WO2005065239A2 (en) | 2003-12-31 | 2004-12-23 | Novel recombinant proteins with n-terminal free thiol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2551131A1 true CA2551131A1 (en) | 2005-07-21 |
Family
ID=34748926
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002551131A Abandoned CA2551131A1 (en) | 2003-12-31 | 2004-12-23 | Novel recombinant proteins with n-terminal free thiol |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20050170457A1 (enExample) |
| EP (1) | EP1699920A4 (enExample) |
| JP (1) | JP2008500275A (enExample) |
| CN (1) | CN1902311A (enExample) |
| AU (1) | AU2004311796A1 (enExample) |
| CA (1) | CA2551131A1 (enExample) |
| WO (1) | WO2005065239A2 (enExample) |
Families Citing this family (97)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010510794A (ja) | 2006-11-28 | 2010-04-08 | ハナル ファーマシューティカル カンパニー リミテッド | 修飾型エリスロポエチンポリペプチド及びこの治療用用途 |
| TW200900420A (en) | 2007-02-02 | 2009-01-01 | Amgen Inc | Hepcidin, hepcidin antagonists and methods of use |
| US8383114B2 (en) * | 2007-09-27 | 2013-02-26 | Amgen Inc. | Pharmaceutical formulations |
| EP3381445B1 (en) | 2007-11-15 | 2023-10-25 | Amgen Inc. | Aqueous formulation of antibody stablised by antioxidants for parenteral administration |
| EP2803675A3 (en) | 2008-01-25 | 2014-12-24 | Amgen, Inc | Ferroportin antibodies and methods of use |
| JP2011519279A (ja) | 2008-05-01 | 2011-07-07 | アムジエン・インコーポレーテツド | 抗ヘプシジン抗体及び使用の方法 |
| WO2010056981A2 (en) | 2008-11-13 | 2010-05-20 | Massachusetts General Hospital | Methods and compositions for regulating iron homeostasis by modulation bmp-6 |
| CA2778105C (en) | 2009-10-23 | 2019-04-02 | Amgen Inc. | Vial adapter and system |
| KR20180037303A (ko) | 2010-06-07 | 2018-04-11 | 암젠 인크 | 약물 전달 장치 |
| AU2012236573B2 (en) | 2011-03-31 | 2016-06-02 | Amgen Inc. | Vial adapter and system |
| US10092706B2 (en) | 2011-04-20 | 2018-10-09 | Amgen Inc. | Autoinjector apparatus |
| EA018116B1 (ru) * | 2011-06-06 | 2013-05-30 | Общество С Ограниченной Ответственностью "Форт" (Ооо "Форт") | Способ получения ковалентного конъюгата полиэтиленгликоля с эритропоэтином |
| LT3045187T (lt) | 2011-10-14 | 2019-07-10 | Amgen Inc. | Injekcijų įrenginys ir surinkimo būdas |
| EP3081249B1 (en) | 2012-11-21 | 2020-12-30 | Amgen Inc. | Drug delivery device |
| WO2014144096A1 (en) | 2013-03-15 | 2014-09-18 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| MX359794B (es) | 2013-03-15 | 2018-10-10 | Intrinsic Lifesciences Llc | Anticuerpos anti-hepcidina y usos de los mismos. |
| EP2968775B1 (en) | 2013-03-15 | 2019-12-18 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| AU2014228177B2 (en) | 2013-03-15 | 2018-04-26 | Amgen Inc. | Body contour adaptable autoinjector device |
| CA2897825C (en) | 2013-03-22 | 2022-05-24 | Scott R. Gibson | Injector and method of assembly |
| WO2015032981A1 (en) * | 2013-09-09 | 2015-03-12 | Lek Pharmaceuticals D.D. | Erythropoietin conjugates having oral bioavailability |
| AU2014340171B2 (en) | 2013-10-24 | 2019-05-30 | Amgen Inc. | Injector and method of assembly |
| CA2926110C (en) | 2013-10-24 | 2023-05-23 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
| WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
| CA3193070A1 (en) | 2014-05-07 | 2015-11-12 | Amgen Inc. | Autoinjector with shock reducing elements |
| KR20170016335A (ko) | 2014-06-03 | 2017-02-13 | 암겐 인코포레이티드 | 약물 전달 디바이스의 사용자를 보조하기 위한 디바이스들 및 방법들 |
| EP3197915A4 (en) | 2014-09-22 | 2018-12-19 | Intrinsic Lifesciences LLC | Humanized anti-hepcidin antibodies and uses thereof |
| MX392725B (es) | 2014-10-14 | 2025-03-24 | Amgen Inc | Dispositivo de inyeccion de farmaco con indicadores visuales y audibles. |
| US20160151511A1 (en) | 2014-12-02 | 2016-06-02 | Antriabio, Inc. | Proteins and protein conjugates with increased hydrophobicity |
| EP3233159B1 (en) | 2014-12-19 | 2020-03-04 | Amgen Inc. | Drug delivery device with live button or user interface field |
| ES2898469T3 (es) | 2014-12-19 | 2022-03-07 | Amgen Inc | Dispositivo de administración de medicamentos con sensor de proximidad |
| AU2016220141B2 (en) | 2015-02-17 | 2018-07-12 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
| EP3261690B1 (en) | 2015-02-27 | 2021-12-15 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
| WO2016196017A1 (en) | 2015-06-04 | 2016-12-08 | Antriabio, Inc. | Amine pegylation methods for the preparation of site-specific protein conjugates |
| WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
| CN105367629B (zh) * | 2015-11-09 | 2019-01-08 | 天津药物研究院有限公司 | 一种促红细胞生成素模拟肽以及其制备方法和用途 |
| ES2755717T3 (es) | 2015-12-09 | 2020-04-23 | Amgen Inc | Autoinyector con tapa de señalización |
| US11154661B2 (en) | 2016-01-06 | 2021-10-26 | Amgen Inc. | Auto-injector with signaling electronics |
| DK3429663T3 (da) | 2016-03-15 | 2020-09-28 | Amgen Inc | Reduktion af sandsynligheden for glasbrud i anordninger til indgivelse af lægemidler |
| WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
| GB2549798A (en) * | 2016-04-29 | 2017-11-01 | Univ Bradford | Peptides and nanoparticle formulations thereof |
| US11389588B2 (en) | 2016-05-02 | 2022-07-19 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
| WO2017197222A1 (en) | 2016-05-13 | 2017-11-16 | Amgen Inc. | Vial sleeve assembly |
| EP3458988B1 (en) | 2016-05-16 | 2023-10-18 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| EP3465124A1 (en) | 2016-06-03 | 2019-04-10 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
| US11285266B2 (en) | 2016-07-01 | 2022-03-29 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
| WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
| WO2018081234A1 (en) | 2016-10-25 | 2018-05-03 | Amgen Inc. | On-body injector |
| MX2019008432A (es) | 2017-01-17 | 2019-11-18 | Amgen Inc | Dispositivos de inyeccion y metodos relacionados de uso y ensamblaje. |
| US11752258B2 (en) | 2017-02-17 | 2023-09-12 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
| MX2019009755A (es) | 2017-02-17 | 2019-10-07 | Amgen Inc | Mecanismo de insercion para dispositivo de suministro de farmacos. |
| AU2018231107B2 (en) | 2017-03-06 | 2023-04-20 | Amgen Inc. | Drug delivery device with activation prevention feature |
| EP3592402A1 (en) | 2017-03-07 | 2020-01-15 | Amgen Inc. | Needle insertion by overpressure |
| EP3592404A1 (en) | 2017-03-09 | 2020-01-15 | Amgen Inc. | Insertion mechanism for drug delivery device |
| JP2020511499A (ja) | 2017-03-20 | 2020-04-16 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 赤血球生成刺激タンパク質のインビトロでの糖鎖改変のための方法 |
| EP4241807B1 (en) | 2017-03-28 | 2025-02-19 | Amgen Inc. | Plunger rod and syringe assembly system |
| AU2018280054B2 (en) | 2017-06-08 | 2023-07-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
| AU2018282077B2 (en) | 2017-06-08 | 2023-11-23 | Amgen Inc. | Torque driven drug delivery device |
| MA49447A (fr) | 2017-06-22 | 2020-04-29 | Amgen Inc | Réduction des impacts/chocs d'activation d'un dispositif |
| WO2018237225A1 (en) | 2017-06-23 | 2018-12-27 | Amgen Inc. | Electronic drug delivery device comprising a cap activated by a switch assembly |
| MA49562A (fr) | 2017-07-14 | 2020-05-20 | Amgen Inc | Système d'insertion-rétractation d'aiguille présentant un système à ressort en double torsion |
| EP3655063A1 (en) | 2017-07-21 | 2020-05-27 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
| EP3658203B2 (en) | 2017-07-25 | 2025-10-01 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
| US11484648B2 (en) | 2017-07-25 | 2022-11-01 | Amgen Inc. | Drug delivery device with container access system and related method of assembly |
| MA49838A (fr) | 2017-08-09 | 2020-06-17 | Amgen Inc | Systèm de administration de médicaments avec pression hydraulique-pneumatique de chambre |
| MA49897A (fr) | 2017-08-18 | 2020-06-24 | Amgen Inc | Injecteur sur-corps avec patch adhésif stérile |
| US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
| MA50611A (fr) | 2017-10-04 | 2020-08-12 | Amgen Inc | Adaptateur d'écoulement destiné à un dispositif d'administration de médicament |
| IL272636B2 (en) | 2017-10-06 | 2024-10-01 | Amgen Inc | Drug delivery device with interlock assembly and related method of assembly |
| IL273323B2 (en) | 2017-10-09 | 2024-10-01 | Amgen Inc | Drug delivery device with drive assembly and related assembly method |
| EP3703778A1 (en) | 2017-11-03 | 2020-09-09 | Amgen Inc. | System and approaches for sterilizing a drug delivery device |
| EP3707075A1 (en) | 2017-11-06 | 2020-09-16 | Amgen Inc. | Fill-finish assemblies and related methods |
| US20200261648A1 (en) | 2017-11-06 | 2020-08-20 | Amgen Inc. | Drug delivery device with placement and flow sensing |
| CN111225696B (zh) | 2017-11-10 | 2023-07-18 | 安进公司 | 用于药物递送装置的柱塞 |
| MX2020005066A (es) | 2017-11-16 | 2020-08-20 | Amgen Inc | Autoinyector con deteccion de detencion y punto final. |
| WO2019099324A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Door latch mechanism for drug delivery device |
| KR102787353B1 (ko) * | 2018-03-02 | 2025-03-26 | 엘리시오 테라퓨틱스, 인크. | 돌연변이 kras 서열 및 지질을 포함하는 화합물 및 이의 용도 |
| US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
| US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
| WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
| WO2020023451A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
| EP3826701A1 (en) | 2018-07-24 | 2021-06-02 | Amgen Inc. | Delivery devices for administering drugs |
| WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
| CA3103105A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Inc. | Fluid path assembly for a drug delivery device |
| MA53724A (fr) | 2018-09-24 | 2021-12-29 | Amgen Inc | Systèmes et procédés de dosage interventionnel |
| CA3110371A1 (en) | 2018-09-28 | 2020-04-02 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
| AU2019352616B2 (en) | 2018-10-02 | 2024-10-10 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
| TW202529830A (zh) | 2018-10-05 | 2025-08-01 | 美商安進公司 | 具有劑量指示器之藥物遞送裝置 |
| SG11202101824VA (en) | 2018-10-15 | 2021-03-30 | Amgen Inc | Platform assembly process for drug delivery device |
| EA202191037A1 (ru) | 2018-10-15 | 2021-08-05 | Эмджен Инк. | Устройство доставки лекарственного средства, имеющее демпферный механизм |
| EP3873563A1 (en) | 2018-11-01 | 2021-09-08 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| TWI831847B (zh) | 2018-11-01 | 2024-02-11 | 美商安進公司 | 部分針頭縮回之藥物遞送裝置及其操作方法 |
| WO2020091956A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| US20220160972A1 (en) | 2019-04-24 | 2022-05-26 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
| WO2021041067A2 (en) | 2019-08-23 | 2021-03-04 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
| WO2022159414A1 (en) | 2021-01-22 | 2022-07-28 | University Of Rochester | Erythropoietin for gastroinfestinal dysfunction |
| EP4341161A1 (en) | 2021-05-21 | 2024-03-27 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
| EP4612312A1 (en) | 2022-11-02 | 2025-09-10 | F. Hoffmann-La Roche AG | Method for producing glycoprotein compositions |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775622A (en) * | 1982-03-08 | 1988-10-04 | Genentech, Inc. | Expression, processing and secretion of heterologous protein by yeast |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| WO1996028471A1 (en) * | 1995-03-14 | 1996-09-19 | Praecis Pharmaceuticals Incorporated | Modulators of amyloid aggregation |
| US5939286A (en) * | 1995-05-10 | 1999-08-17 | University Of Florida | Hybrid interferon tau/alpha polypeptides, their recombinant production, and methods using them |
| US6015662A (en) * | 1996-01-23 | 2000-01-18 | Abbott Laboratories | Reagents for use as calibrators and controls |
| US6083725A (en) * | 1996-09-13 | 2000-07-04 | Transkaryotic Therapies, Inc. | Tranfected human cells expressing human α-galactosidase A protein |
| WO1998013007A2 (en) * | 1996-09-26 | 1998-04-02 | University Of Southern California | Methods and compositions for lipidization of hydrophilic molecules |
| US6608183B1 (en) * | 1997-07-14 | 2003-08-19 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
| US6433145B1 (en) * | 1998-07-21 | 2002-08-13 | Human Genome Sciences, Inc. | Keratinocyte derived interferon |
| BR0008759B1 (pt) * | 1999-01-14 | 2014-03-11 | Bolder Biotechnology Inc | Métodos para a produção de proteinas contendo resíduos de cisteina livre |
| NZ522847A (en) * | 2000-05-16 | 2004-11-26 | Bolder Biotechnology Inc | Methods for refolding proteins containing free cysteine residues |
| US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| WO2003055526A2 (en) * | 2001-12-21 | 2003-07-10 | Maxygen Aps | Erythropoietin conjugates |
| US7074755B2 (en) * | 2003-05-17 | 2006-07-11 | Centocor, Inc. | Erythropoietin conjugate compounds with extended half-lives |
| EP1641481A4 (en) * | 2003-05-30 | 2008-10-15 | Centocor Inc | TRAINING OF NEW ERYTHROPOIETIN CONJUGATES USING TRANSGLUTAMINASE |
-
2004
- 2004-12-23 CA CA002551131A patent/CA2551131A1/en not_active Abandoned
- 2004-12-23 US US11/021,516 patent/US20050170457A1/en not_active Abandoned
- 2004-12-23 WO PCT/US2004/043081 patent/WO2005065239A2/en not_active Ceased
- 2004-12-23 EP EP04815195A patent/EP1699920A4/en not_active Withdrawn
- 2004-12-23 JP JP2006547297A patent/JP2008500275A/ja active Pending
- 2004-12-23 AU AU2004311796A patent/AU2004311796A1/en not_active Abandoned
- 2004-12-23 CN CNA2004800396501A patent/CN1902311A/zh active Pending
-
2009
- 2009-06-02 US US12/476,268 patent/US20090239790A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20050170457A1 (en) | 2005-08-04 |
| AU2004311796A1 (en) | 2005-07-21 |
| WO2005065239A3 (en) | 2005-11-24 |
| WO2005065239A2 (en) | 2005-07-21 |
| CN1902311A (zh) | 2007-01-24 |
| JP2008500275A (ja) | 2008-01-10 |
| EP1699920A2 (en) | 2006-09-13 |
| WO2005065239A8 (en) | 2006-08-17 |
| EP1699920A4 (en) | 2008-05-28 |
| US20090239790A1 (en) | 2009-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2551131A1 (en) | Novel recombinant proteins with n-terminal free thiol | |
| JP5517844B2 (ja) | 単離された単ｐｅｇ化ヒト成長ホルモンタンパク質及び医薬品の製造におけるその使用 | |
| CN1318443C (zh) | 含游离半胱氨酸残基的蛋白重折叠的方法 | |
| JP4656814B2 (ja) | エリスロポエチンコンジュゲート | |
| JPH08506247A (ja) | 組換えｃｔｌａ４ポリペプチドおよびその製造方法 | |
| KR20070072924A (ko) | 화학적으로 개질된 인간 성장 호르몬 콘쥬게이트 | |
| US12491258B2 (en) | Method for preparing long-acting drug conjugate through preparation of intermediate | |
| CN101965199B (zh) | 含硒的改性剂和缀合物 | |
| CN102131825A (zh) | 具有延长的循环半衰期的n-糖基化的人生长激素 | |
| EP3863680A1 (en) | Oligomer extended insulin-fc conjugates and their medical use | |
| KR100554490B1 (ko) | 분자내 샤퍼론 유사 서열을 함유하는 키메라 단백질 및이것의 인슐린 제조용 용도 | |
| WO2013022328A1 (en) | Derivatives of recombinant proteins, homo-multimers of granulocyte colony-stimulating factor and method of preparation thereof | |
| HK40067345B (en) | Method for preparing long-acting drug conjugate through preparation of novel intermediate | |
| HK40067345A (en) | Method for preparing long-acting drug conjugate through preparation of novel intermediate | |
| KR20210009980A (ko) | 단백질 결합체의 신규 제조 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |