AU634517B2 - Somatotropin analogs - Google Patents

Somatotropin analogs

Info

Publication number: AU634517B2
Authority: AU; Australia
Prior art keywords: rbst; somatotropin; animal; asparagine; serine
Prior art date: 1989-01-19
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.): Ceased

Application number

AU49427/90A

Other languages

English (en)

Other versions

AU4942790A (en

Inventor

Robert L. Garlick

Stephen B. Lyle

John E. Mott

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pharmacia and Upjohn Co

Original Assignee

Upjohn Co

Priority date (The priority date 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 date listed.)

1989-01-19

Filing date

1989-12-11

Publication date

1993-02-25

1989-12-11 Application filed by Upjohn Co filed Critical Upjohn Co

1990-08-13 Publication of AU4942790A publication Critical patent/AU4942790A/en

1993-02-25 Application granted granted Critical

1993-02-25 Publication of AU634517B2 publication Critical patent/AU634517B2/en

1997-04-24 Assigned to PHARMACIA & UPJOHN COMPANY reassignment PHARMACIA & UPJOHN COMPANY Request to Amend Deed and Register Assignors: UPJOHN COMPANY, THE

2009-12-11 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

108010051696 Growth Hormone Proteins 0.000 title claims description 35
102000018997 Growth Hormone Human genes 0.000 title claims 18
241000283690 Bos taurus Species 0.000 claims description 45
241001465754 Metazoa Species 0.000 claims description 41
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 30
235000009582 asparagine Nutrition 0.000 claims description 30
229960001230 asparagine Drugs 0.000 claims description 30
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 23
238000000034 method Methods 0.000 claims description 22
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 21
108010006025 bovine growth hormone Proteins 0.000 claims description 15
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 14
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 claims description 14
235000013336 milk Nutrition 0.000 claims description 13
239000008267 milk Substances 0.000 claims description 13
210000004080 milk Anatomy 0.000 claims description 13
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 12
239000004471 Glycine Substances 0.000 claims description 10
235000001014 amino acid Nutrition 0.000 claims description 10
229940024606 amino acid Drugs 0.000 claims description 8
150000001413 amino acids Chemical class 0.000 claims description 8
230000001965 increasing effect Effects 0.000 claims description 6
241000282693 Cercopithecidae Species 0.000 claims description 4
241000283073 Equus caballus Species 0.000 claims description 4
241000282414 Homo sapiens Species 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
241000251468 Actinopterygii Species 0.000 claims description 3
230000002708 enhancing effect Effects 0.000 claims description 3
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 2
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 1
238000002347 injection Methods 0.000 description 24
239000007924 injection Substances 0.000 description 24
108090000623 proteins and genes Proteins 0.000 description 23
108020004414 DNA Proteins 0.000 description 21
102100038803 Somatotropin Human genes 0.000 description 17
239000013598 vector Substances 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
238000011534 incubation Methods 0.000 description 14
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 13
241000700159 Rattus Species 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
235000004400 serine Nutrition 0.000 description 12
239000000872 buffer Substances 0.000 description 11
230000036515 potency Effects 0.000 description 10
235000013930 proline Nutrition 0.000 description 10
241000894007 species Species 0.000 description 10
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 9
125000003275 alpha amino acid group Chemical group 0.000 description 9
238000009396 hybridization Methods 0.000 description 9
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 8
125000000539 amino acid group Chemical group 0.000 description 8
235000003704 aspartic acid Nutrition 0.000 description 8
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 8
230000008859 change Effects 0.000 description 8
239000000203 mixture Substances 0.000 description 8
235000018102 proteins Nutrition 0.000 description 8
102000004169 proteins and genes Human genes 0.000 description 8
239000000523 sample Substances 0.000 description 8
239000000243 solution Substances 0.000 description 8
239000002253 acid Substances 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
239000013612 plasmid Substances 0.000 description 7
230000007017 scission Effects 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
238000010367 cloning Methods 0.000 description 6
239000012634 fragment Substances 0.000 description 6
230000000977 initiatory effect Effects 0.000 description 6
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
238000003860 storage Methods 0.000 description 6
206010062767 Hypophysitis Diseases 0.000 description 5
108091000080 Phosphotransferase Proteins 0.000 description 5
235000015278 beef Nutrition 0.000 description 5
235000013365 dairy product Nutrition 0.000 description 5
235000013922 glutamic acid Nutrition 0.000 description 5
239000004220 glutamic acid Substances 0.000 description 5
244000005700 microbiome Species 0.000 description 5
238000002703 mutagenesis Methods 0.000 description 5
231100000350 mutagenesis Toxicity 0.000 description 5
102000020233 phosphotransferase Human genes 0.000 description 5
210000003635 pituitary gland Anatomy 0.000 description 5
102000053602 DNA Human genes 0.000 description 4
108091034117 Oligonucleotide Proteins 0.000 description 4
230000027455 binding Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
230000006651 lactation Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000004007 reversed phase HPLC Methods 0.000 description 4
238000012163 sequencing technique Methods 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
108091028043 Nucleic acid sequence Proteins 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
108010011559 alanylphenylalanine Proteins 0.000 description 3
230000037396 body weight Effects 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
239000000122 growth hormone Substances 0.000 description 3
239000007943 implant Substances 0.000 description 3
230000006698 induction Effects 0.000 description 3
238000002955 isolation Methods 0.000 description 3
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
231100000219 mutagenic Toxicity 0.000 description 3
230000003505 mutagenic effect Effects 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
239000000047 product Substances 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
238000002741 site-directed mutagenesis Methods 0.000 description 3
238000003307 slaughter Methods 0.000 description 3
238000007619 statistical method Methods 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
238000011282 treatment Methods 0.000 description 3
238000005406 washing Methods 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
102100034343 Integrase Human genes 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
239000000020 Nitrocellulose Substances 0.000 description 2
241001494479 Pecora Species 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
241000282849 Ruminantia Species 0.000 description 2
VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 2
XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
238000000211 autoradiogram Methods 0.000 description 2
238000004166 bioassay Methods 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000000295 complement effect Effects 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
239000000284 extract Substances 0.000 description 2
235000019688 fish Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000012239 gene modification Methods 0.000 description 2
230000005017 genetic modification Effects 0.000 description 2
235000013617 genetically modified food Nutrition 0.000 description 2
239000012145 high-salt buffer Substances 0.000 description 2
230000006338 isoaspartate formation Effects 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
229920001220 nitrocellulos Polymers 0.000 description 2
230000001817 pituitary effect Effects 0.000 description 2
230000008569 process Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
101150002764 purA gene Proteins 0.000 description 2
238000012216 screening Methods 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
AXFMEGAFCUULFV-BLFANLJRSA-N (2s)-2-[[(2s)-1-[(2s,3r)-2-amino-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]pentanedioic acid Chemical compound CC[C@@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AXFMEGAFCUULFV-BLFANLJRSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 1
241000186361 Actinobacteria <class> Species 0.000 description 1
DKJPOZOEBONHFS-ZLUOBGJFSA-N Ala-Ala-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O DKJPOZOEBONHFS-ZLUOBGJFSA-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
DYWZQNMGPYXVNS-SRVKXCTJSA-N Ala-Leu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O DYWZQNMGPYXVNS-SRVKXCTJSA-N 0.000 description 1
AWNAEZICPNGAJK-FXQIFTODSA-N Ala-Met-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(O)=O AWNAEZICPNGAJK-FXQIFTODSA-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
AUFACLFHBAGZEN-ZLUOBGJFSA-N Ala-Ser-Cys Chemical compound N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O AUFACLFHBAGZEN-ZLUOBGJFSA-N 0.000 description 1
239000004254 Ammonium phosphate Substances 0.000 description 1
KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 1
MJINRRBEMOLJAK-DCAQKATOSA-N Arg-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N MJINRRBEMOLJAK-DCAQKATOSA-N 0.000 description 1
OGZBJJLRKQZRHL-KJEVXHAQSA-N Arg-Thr-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OGZBJJLRKQZRHL-KJEVXHAQSA-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
ANAHQDPQQBDOBM-UHFFFAOYSA-N Arg-Val-Tyr Natural products CC(C)C(NC(=O)C(N)CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O ANAHQDPQQBDOBM-UHFFFAOYSA-N 0.000 description 1
QEYJFBMTSMLPKZ-ZKWXMUAHSA-N Asn-Ala-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O QEYJFBMTSMLPKZ-ZKWXMUAHSA-N 0.000 description 1
ICDDSTLEMLGSTB-GUBZILKMSA-N Asn-Met-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ICDDSTLEMLGSTB-GUBZILKMSA-N 0.000 description 1
DWOGMPWRQQWPPF-GUBZILKMSA-N Asp-Leu-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O DWOGMPWRQQWPPF-GUBZILKMSA-N 0.000 description 1
241000972773 Aulopiformes Species 0.000 description 1
241000271566 Aves Species 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
UKVGHFORADMBEN-GUBZILKMSA-N Cys-Arg-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UKVGHFORADMBEN-GUBZILKMSA-N 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
230000004568 DNA-binding Effects 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
GMGKDVVBSVVKCT-NUMRIWBASA-N Gln-Asn-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GMGKDVVBSVVKCT-NUMRIWBASA-N 0.000 description 1
IWUFOVSLWADEJC-AVGNSLFASA-N Gln-His-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O IWUFOVSLWADEJC-AVGNSLFASA-N 0.000 description 1
FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 description 1
XZUUUKNKNWVPHQ-JYJNAYRXSA-N Gln-Phe-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O XZUUUKNKNWVPHQ-JYJNAYRXSA-N 0.000 description 1
ZZLDMBMFKZFQMU-NRPADANISA-N Gln-Val-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O ZZLDMBMFKZFQMU-NRPADANISA-N 0.000 description 1
CUXJIASLBRJOFV-LAEOZQHASA-N Glu-Gly-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUXJIASLBRJOFV-LAEOZQHASA-N 0.000 description 1
JDUKCSSHWNIQQZ-IHRRRGAJSA-N Glu-Phe-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O JDUKCSSHWNIQQZ-IHRRRGAJSA-N 0.000 description 1
DTRUBYPMMVPQPD-YUMQZZPRSA-N Gly-Gln-Arg Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DTRUBYPMMVPQPD-YUMQZZPRSA-N 0.000 description 1
UHPAZODVFFYEEL-QWRGUYRKSA-N Gly-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN UHPAZODVFFYEEL-QWRGUYRKSA-N 0.000 description 1
HFPVRZWORNJRRC-UWVGGRQHSA-N Gly-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN HFPVRZWORNJRRC-UWVGGRQHSA-N 0.000 description 1
MYXNLWDWWOTERK-BHNWBGBOSA-N Gly-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN)O MYXNLWDWWOTERK-BHNWBGBOSA-N 0.000 description 1
VHHYJBSXXMPQGZ-AVGNSLFASA-N His-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N VHHYJBSXXMPQGZ-AVGNSLFASA-N 0.000 description 1
IITVUURPOYGCTD-NAKRPEOUSA-N Ile-Pro-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IITVUURPOYGCTD-NAKRPEOUSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
YUGVQABRIJXYNQ-UHFFFAOYSA-N Leu-Ala-Ala Natural products CC(C)CC(N)C(=O)NC(C)C(=O)NC(C)C(O)=O YUGVQABRIJXYNQ-UHFFFAOYSA-N 0.000 description 1
LSPYFSHXDAYVDI-SRVKXCTJSA-N Leu-Ala-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(C)C LSPYFSHXDAYVDI-SRVKXCTJSA-N 0.000 description 1
JUWJEAPUNARGCF-DCAQKATOSA-N Leu-Arg-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O JUWJEAPUNARGCF-DCAQKATOSA-N 0.000 description 1
UILIPCLTHRPCRB-XUXIUFHCSA-N Leu-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)N UILIPCLTHRPCRB-XUXIUFHCSA-N 0.000 description 1
HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-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
KVOFSTUWVSQMDK-KKUMJFAQSA-N Leu-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CN=CN1 KVOFSTUWVSQMDK-KKUMJFAQSA-N 0.000 description 1
AUBMZAMQCOYSIC-MNXVOIDGSA-N Leu-Ile-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O AUBMZAMQCOYSIC-MNXVOIDGSA-N 0.000 description 1
ZDBMWELMUCLUPL-QEJZJMRPSA-N Leu-Phe-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 ZDBMWELMUCLUPL-QEJZJMRPSA-N 0.000 description 1
RGUXWMDNCPMQFB-YUMQZZPRSA-N Leu-Ser-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RGUXWMDNCPMQFB-YUMQZZPRSA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
QYOXSYXPHUHOJR-GUBZILKMSA-N Lys-Asn-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYOXSYXPHUHOJR-GUBZILKMSA-N 0.000 description 1
PXHCFKXNSBJSTQ-KKUMJFAQSA-N Lys-Asn-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)O PXHCFKXNSBJSTQ-KKUMJFAQSA-N 0.000 description 1
HEWWNLVEWBJBKA-WDCWCFNPSA-N Lys-Gln-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCCN HEWWNLVEWBJBKA-WDCWCFNPSA-N 0.000 description 1
RBEATVHTWHTHTJ-KKUMJFAQSA-N Lys-Leu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O RBEATVHTWHTHTJ-KKUMJFAQSA-N 0.000 description 1
MGKFCQFVPKOWOL-CIUDSAMLSA-N Lys-Ser-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N MGKFCQFVPKOWOL-CIUDSAMLSA-N 0.000 description 1
CTVJSFRHUOSCQQ-DCAQKATOSA-N Met-Arg-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CTVJSFRHUOSCQQ-DCAQKATOSA-N 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
SWZKMTDPQXLQRD-XVSYOHENSA-N Phe-Asp-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWZKMTDPQXLQRD-XVSYOHENSA-N 0.000 description 1
HPECNYCQLSVCHH-BZSNNMDCSA-N Phe-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N HPECNYCQLSVCHH-BZSNNMDCSA-N 0.000 description 1
ZLGQEBCCANLYRA-RYUDHWBXSA-N Phe-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O ZLGQEBCCANLYRA-RYUDHWBXSA-N 0.000 description 1
QPVFUAUFEBPIPT-CDMKHQONSA-N Phe-Gly-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O QPVFUAUFEBPIPT-CDMKHQONSA-N 0.000 description 1
JHSRGEODDALISP-XVSYOHENSA-N Phe-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O JHSRGEODDALISP-XVSYOHENSA-N 0.000 description 1
DCHQYSOGURGJST-FJXKBIBVSA-N Pro-Thr-Gly Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O DCHQYSOGURGJST-FJXKBIBVSA-N 0.000 description 1
108010003201 RGH 0205 Proteins 0.000 description 1
108010025216 RVF peptide Proteins 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
HBOABDXGTMMDSE-GUBZILKMSA-N Ser-Arg-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O HBOABDXGTMMDSE-GUBZILKMSA-N 0.000 description 1
CNIIKZQXBBQHCX-FXQIFTODSA-N Ser-Asp-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O CNIIKZQXBBQHCX-FXQIFTODSA-N 0.000 description 1
MESDJCNHLZBMEP-ZLUOBGJFSA-N Ser-Asp-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MESDJCNHLZBMEP-ZLUOBGJFSA-N 0.000 description 1
XSYJDGIDKRNWFX-SRVKXCTJSA-N Ser-Cys-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O XSYJDGIDKRNWFX-SRVKXCTJSA-N 0.000 description 1
GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 1
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 1
IXZHZUGGKLRHJD-DCAQKATOSA-N Ser-Leu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IXZHZUGGKLRHJD-DCAQKATOSA-N 0.000 description 1
FVFUOQIYDPAIJR-XIRDDKMYSA-N Ser-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CO)N FVFUOQIYDPAIJR-XIRDDKMYSA-N 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
101150104425 T4 gene Proteins 0.000 description 1
XOTBWOCSLMBGMF-SUSMZKCASA-N Thr-Glu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOTBWOCSLMBGMF-SUSMZKCASA-N 0.000 description 1
VGYVVSQFSSKZRJ-OEAJRASXSA-N Thr-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=CC=C1 VGYVVSQFSSKZRJ-OEAJRASXSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
JFDGVHXRCKEBAU-KKUMJFAQSA-N Tyr-Asp-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N)O JFDGVHXRCKEBAU-KKUMJFAQSA-N 0.000 description 1
QSFJHIRIHOJRKS-ULQDDVLXSA-N Tyr-Leu-Arg 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](CCCNC(N)=N)C(O)=O QSFJHIRIHOJRKS-ULQDDVLXSA-N 0.000 description 1
UEPLNXPLHJUYPT-AVGNSLFASA-N Val-Met-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(O)=O UEPLNXPLHJUYPT-AVGNSLFASA-N 0.000 description 1
PFMSJVIPEZMKSC-DZKIICNBSA-N Val-Tyr-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PFMSJVIPEZMKSC-DZKIICNBSA-N 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
208000021017 Weight Gain Diseases 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
230000006978 adaptation Effects 0.000 description 1
238000013019 agitation Methods 0.000 description 1
108010044940 alanylglutamine Proteins 0.000 description 1
KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
229910000148 ammonium phosphate Inorganic materials 0.000 description 1
235000019289 ammonium phosphates Nutrition 0.000 description 1
238000005571 anion exchange chromatography Methods 0.000 description 1
108010036533 arginylvaline Proteins 0.000 description 1
230000001174 ascending effect Effects 0.000 description 1
235000021052 average daily weight gain Nutrition 0.000 description 1
230000008901 benefit Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000010504 bond cleavage reaction Methods 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
238000012790 confirmation Methods 0.000 description 1
238000010276 construction Methods 0.000 description 1
RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
239000007857 degradation product Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
230000004927 fusion Effects 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
102000034238 globular proteins Human genes 0.000 description 1
108091005896 globular proteins Proteins 0.000 description 1
108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 1
108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
108010049041 glutamylalanine Proteins 0.000 description 1
108010066198 glycyl-leucyl-phenylalanine Proteins 0.000 description 1
244000309465 heifer Species 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000001155 isoelectric focusing Methods 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
108010049589 leucyl-leucyl-leucine Proteins 0.000 description 1
108010034529 leucyl-lysine Proteins 0.000 description 1
108010091871 leucylmethionine Proteins 0.000 description 1
238000011068 loading method Methods 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000013372 meat Nutrition 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
210000004738 parenchymal cell Anatomy 0.000 description 1
239000008188 pellet Substances 0.000 description 1
108010051242 phenylalanylserine Proteins 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000004481 post-translational protein modification Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108010004914 prolylarginine Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
235000019515 salmon Nutrition 0.000 description 1
229920006298 saran Polymers 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
238000013223 sprague-dawley female rat Methods 0.000 description 1
239000012089 stop solution Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
101150108727 trpl gene Proteins 0.000 description 1
239000004474 valine Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
NLIVDORGVGAOOJ-MAHBNPEESA-M xylene cyanol Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(\C=1C(=CC(OS([O-])=O)=CC=1)OS([O-])=O)=C\1C=C(C)\C(=[NH+]/CC)\C=C/1 NLIVDORGVGAOOJ-MAHBNPEESA-M 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Gastroenterology & Hepatology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Endocrinology (AREA)
Toxicology (AREA)
Zoology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Cosmetics (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

AU49427/90A 1989-01-19 1989-12-11 Somatotropin analogs Ceased AU634517B2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US29910789A	1989-01-19	1989-01-19
US299107		1989-01-19

Publications (2)

Publication Number	Publication Date
AU4942790A AU4942790A (en)	1990-08-13
AU634517B2 true AU634517B2 (en)	1993-02-25

Family

ID=23153338

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU49427/90A Ceased AU634517B2 (en)	1989-01-19	1989-12-11	Somatotropin analogs

Country Status (7)

Country	Link
EP (1)	EP0454730A1 (da)
JP (1)	JPH04502762A (da)
KR (1)	KR910700264A (da)
AU (1)	AU634517B2 (da)
CA (1)	CA2005358A1 (da)
DK (1)	DK136991D0 (da)
WO (1)	WO1990008164A1 (da)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE198353T1 (de) *	1988-08-24	2001-01-15	American Cyanamid Co	Stabilisierung von somatotropinen durch modifikation von cystein-resten durch orts- spezifische mutagenese oder chemische derivatisierung
ZA936811B (en) *	1992-10-28	1995-03-15	Upjohn Co	Somatotropin modifications
US7214660B2 (en)	2001-10-10	2007-05-08	Neose Technologies, Inc.	Erythropoietin: remodeling and glycoconjugation of erythropoietin
AU2004236174B2 (en)	2001-10-10	2011-06-02	Novo Nordisk A/S	Glycopegylation methods and proteins/peptides produced by the methods
US8008252B2 (en)	2001-10-10	2011-08-30	Novo Nordisk A/S	Factor VII: remodeling and glycoconjugation of Factor VII
US7696163B2 (en)	2001-10-10	2010-04-13	Novo Nordisk A/S	Erythropoietin: remodeling and glycoconjugation of erythropoietin
US7795210B2 (en)	2001-10-10	2010-09-14	Novo Nordisk A/S	Protein remodeling methods and proteins/peptides produced by the methods
US7173003B2 (en)	2001-10-10	2007-02-06	Neose Technologies, Inc.	Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
CN102212019B (zh)	2003-03-14	2015-05-27	蔚所番有限公司	支化水溶性聚合物及其缀合物
US7932364B2 (en)	2003-05-09	2011-04-26	Novo Nordisk A/S	Compositions and methods for the preparation of human growth hormone glycosylation mutants
WO2005012484A2 (en)	2003-07-25	2005-02-10	Neose Technologies, Inc.	Antibody-toxin conjugates
US8633157B2 (en)	2003-11-24	2014-01-21	Novo Nordisk A/S	Glycopegylated erythropoietin
US20080305992A1 (en)	2003-11-24	2008-12-11	Neose Technologies, Inc.	Glycopegylated erythropoietin
US7842661B2 (en)	2003-11-24	2010-11-30	Novo Nordisk A/S	Glycopegylated erythropoietin formulations
US7956032B2 (en)	2003-12-03	2011-06-07	Novo Nordisk A/S	Glycopegylated granulocyte colony stimulating factor
KR101439880B1 (ko)	2004-01-08	2014-09-12	라티오팜 게엠베하	펩티드의 오-결합형 글리코실화
US20080300173A1 (en)	2004-07-13	2008-12-04	Defrees Shawn	Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1]
WO2006031811A2 (en)	2004-09-10	2006-03-23	Neose Technologies, Inc.	Glycopegylated interferon alpha
SI2586456T1 (sl)	2004-10-29	2016-05-31	Ratiopharm Gmbh	Preoblikovanje in glikopegliacija fibroblastnega rastnega faktorja (FGF)
WO2006074467A2 (en)	2005-01-10	2006-07-13	Neose Technologies, Inc.	Glycopegylated granulocyte colony stimulating factor
EP1871795A4 (en)	2005-04-08	2010-03-31	Biogenerix Ag	COMPOSITIONS AND METHOD FOR PRODUCING GLYCOSYLATION MUTANTS OF A PROTEASE-RESISTANT HUMAN GROWTH HORMONE
US20070105755A1 (en)	2005-10-26	2007-05-10	Neose Technologies, Inc.	One pot desialylation and glycopegylation of therapeutic peptides
WO2007056191A2 (en)	2005-11-03	2007-05-18	Neose Technologies, Inc.	Nucleotide sugar purification using membranes
EP2049144B8 (en)	2006-07-21	2015-02-18	ratiopharm GmbH	Glycosylation of peptides via o-linked glycosylation sequences
US20100075375A1 (en)	2006-10-03	2010-03-25	Novo Nordisk A/S	Methods for the purification of polypeptide conjugates
JP2010523582A (ja)	2007-04-03	2010-07-15	バイオジェネリクスアクチェンゲゼルシャフト	グリコｐｅｇ化ｇ−ｃｓｆを用いた治療方法
CA2690611C (en)	2007-06-12	2015-12-08	Novo Nordisk A/S	Improved process for the production of nucleotide sugars
US8207112B2 (en)	2007-08-29	2012-06-26	Biogenerix Ag	Liquid formulation of G-CSF conjugate
PL2257311T3 (pl)	2008-02-27	2014-09-30	Novo Nordisk As	Koniugaty cząsteczek czynnika VIII

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1987001708A2 (en) *	1985-09-18	1987-03-26	The Upjohn Company	Enhanced bioactivity of mammalian somatotropin through selective deamidation
EP0075444B1 (en) *	1981-09-18	1992-12-23	Genentech, Inc.	Methods and products for facile microbial expression of dna sequences

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0085036A1 (en) *	1982-01-18	1983-08-03	Monsanto Company	Method for improved bovine milk production
US4446235A (en) *	1982-03-22	1984-05-01	Genentech, Inc.	Method for cloning human growth hormone varient genes
US5104806A (en) *	1987-03-12	1992-04-14	Amgen, Inc.	Porcine growth hormone analogs encoding dna

1989
- 1989-12-11 JP JP2502084A patent/JPH04502762A/ja active Pending
- 1989-12-11 KR KR1019900702070A patent/KR910700264A/ko not_active Application Discontinuation
- 1989-12-11 WO PCT/US1989/005447 patent/WO1990008164A1/en not_active Application Discontinuation
- 1989-12-11 AU AU49427/90A patent/AU634517B2/en not_active Ceased
- 1989-12-11 EP EP90901997A patent/EP0454730A1/en not_active Withdrawn
- 1989-12-13 CA CA002005358A patent/CA2005358A1/en not_active Abandoned
1991
- 1991-07-17 DK DK911369A patent/DK136991D0/da not_active Application Discontinuation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0075444B1 (en) *	1981-09-18	1992-12-23	Genentech, Inc.	Methods and products for facile microbial expression of dna sequences
WO1987001708A2 (en) *	1985-09-18	1987-03-26	The Upjohn Company	Enhanced bioactivity of mammalian somatotropin through selective deamidation

Also Published As

Publication number	Publication date
DK136991A (da)	1991-07-17
AU4942790A (en)	1990-08-13
DK136991D0 (da)	1991-07-17
EP0454730A1 (en)	1991-11-06
JPH04502762A (ja)	1992-05-21
WO1990008164A1 (en)	1990-07-26
CA2005358A1 (en)	1990-07-19
KR910700264A (ko)	1991-03-14

Publication	Publication Date	Title
AU634517B2 (en)	1993-02-25	Somatotropin analogs
JP3207416B2 (ja)	2001-09-10	ソマトトロピン・アナログ類
EP0228449B1 (en)	1994-08-31	Fibroblast growth factor
EP0193515B1 (en)	1996-08-14	Method for obtaining biologically active bovine and porcine growth hormone and composition comprising biologically active porcine growth hormone
CA1340455C (en)	1999-03-23	Human preproinsulin-like growth factor i
US4861868A (en)	1989-08-29	Production of proteins in procaryotes
US5464774A (en)	1995-11-07	Bovine basic fibroblast growth factor
Keshet et al.	1981	Cloning of bovine growth hormone gene and its expression in bacteria
US5631227A (en)	1997-05-20	Somatotropin analogs
FI81378B (fi)	1990-06-29	Dna som kodar foer en prekursor till hpgrf, expressionsvektor och foerfarande foer expression av en prekursor till hpgrf.
AU639245B2 (en)	1993-07-22	Somatotropin analogs
US5141922A (en)	1992-08-25	Biologically active proteins and a method for their use
EP0282319B1 (en)	1993-09-22	Porcine growth hormone analogs
EP0236452B1 (en)	1990-10-31	Enhanced bioactivity of mammalian somatotropin through selective deamidation
EP0263206B1 (en)	1990-12-12	Enhanced bioactivity of mammalian somatotropin through selective deamidation
AU647374B2 (en)	1994-03-24	Sheep growth hormone
KR20070035483A (ko)	2007-03-30	태반 및 뇌하수체 아형 유래의 키메라 인간 성장 호르몬 및상기 키메라의 제조 방법