JPS58190398A - インシユリンへのプレプロインシユリン類似体の変換法 - Google Patents

インシユリンへのプレプロインシユリン類似体の変換法

Info

Publication number: JPS58190398A
Authority: JP; Japan
Prior art keywords: insulin; ester; amino acid; preproinsulin; trypsin
Prior art date: 1982-03-13
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.): Granted

Application number

JP58039298A

Other languages

English (en)

Japanese (ja)

Other versions

JPH0536034B2 (2

Inventor

ライネル・オ−ベルマイア−

ロルフ・ガイゲル

ウルリツヒ・グラウ

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.)

Hoechst AG

Original Assignee

Hoechst AG

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.)

1982-03-13

Filing date

1983-03-11

Publication date

1983-11-07

1983-03-11 Application filed by Hoechst AG filed Critical Hoechst AG

1983-11-07 Publication of JPS58190398A publication Critical patent/JPS58190398A/ja

1993-05-28 Publication of JPH0536034B2 publication Critical patent/JPH0536034B2/ja

Status Granted legal-status Critical Current

Links

108090001061 Insulin Proteins 0.000 title claims abstract description 27
102000004877 Insulin Human genes 0.000 title claims abstract description 27
108010066381 preproinsulin Proteins 0.000 title claims abstract description 14
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 54
229940125396 insulin Drugs 0.000 title claims description 25
238000006243 chemical reaction Methods 0.000 title claims description 13
238000000034 method Methods 0.000 claims abstract description 32
102000004142 Trypsin Human genes 0.000 claims abstract description 14
108090000631 Trypsin Proteins 0.000 claims abstract description 14
239000012588 trypsin Substances 0.000 claims abstract description 14
150000001413 amino acids Chemical class 0.000 claims abstract description 11
150000002148 esters Chemical class 0.000 claims abstract description 11
125000004185 ester group Chemical group 0.000 claims abstract description 5
-1 amino acid ester Chemical class 0.000 claims description 10
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
102000004190 Enzymes Human genes 0.000 claims description 5
108090000790 Enzymes Proteins 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 4
150000003862 amino acid derivatives Chemical class 0.000 claims description 2
239000000758 substrate Substances 0.000 claims description 2
238000000855 fermentation Methods 0.000 claims 1
230000004151 fermentation Effects 0.000 claims 1
125000006239 protecting group Chemical group 0.000 abstract description 6
238000002360 preparation method Methods 0.000 abstract description 3
230000001810 trypsinlike Effects 0.000 abstract description 2
239000004026 insulin derivative Substances 0.000 abstract 2
102000005593 Endopeptidases Human genes 0.000 abstract 1
108010059378 Endopeptidases Proteins 0.000 abstract 1
229940024606 amino acid Drugs 0.000 description 16
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 9
101001011741 Bos taurus Insulin Proteins 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
101000976075 Homo sapiens Insulin Proteins 0.000 description 8
108010076181 Proinsulin Proteins 0.000 description 8
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 8
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 8
241000283690 Bos taurus Species 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
238000007056 transamidation reaction Methods 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
108010075254 C-Peptide Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
108010005991 Pork Regular Insulin Proteins 0.000 description 2
239000004473 Threonine Substances 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
238000010353 genetic engineering Methods 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
229960002898 threonine Drugs 0.000 description 2
150000003587 threonine derivatives Chemical class 0.000 description 2
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 2
HSQIYOPBCOPMSS-ZETCQYMHSA-N (2s)-5-(diaminomethylideneamino)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCN=C(N)N HSQIYOPBCOPMSS-ZETCQYMHSA-N 0.000 description 1
CXQODNIBUNQWAS-CIUDSAMLSA-N Ala-Gln-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CXQODNIBUNQWAS-CIUDSAMLSA-N 0.000 description 1
241000024188 Andala Species 0.000 description 1
239000000592 Artificial Cell Substances 0.000 description 1
102000003670 Carboxypeptidase B Human genes 0.000 description 1
108090000087 Carboxypeptidase B Proteins 0.000 description 1
108010042407 Endonucleases Proteins 0.000 description 1
102000004533 Endonucleases Human genes 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
102000003939 Membrane transport proteins Human genes 0.000 description 1
108090000301 Membrane transport proteins Proteins 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
FBVSXKMMQOZUNU-NSHDSACASA-N N2,N6-Bis{[(2-methyl-2-propanyl)oxy]carbonyl}lysine Chemical compound CC(C)(C)OC(=O)NCCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C FBVSXKMMQOZUNU-NSHDSACASA-N 0.000 description 1
206010029719 Nonspecific reaction Diseases 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
101000993800 Sus scrofa Insulin Proteins 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
108010049705 endonuclease R Proteins 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000011534 incubation Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229940124280 l-arginine Drugs 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000009061 membrane transport Effects 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
TVHCXXXXQNWQLP-DMTCNVIQSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound COC(=O)[C@@H](N)[C@@H](C)O TVHCXXXXQNWQLP-DMTCNVIQSA-N 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
229940025656 proin Drugs 0.000 description 1
238000011403 purification operation Methods 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
XASPGLPXANLVTJ-RITPCOANSA-N tert-butyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound C[C@@H](O)[C@H](N)C(=O)OC(C)(C)C XASPGLPXANLVTJ-RITPCOANSA-N 0.000 description 1
230000014616 translation Effects 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/26—Containing cys-cys disulfide bridge between nonadjacent cysteine residues

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Zoology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Engineering & Computer Science (AREA)
Biophysics (AREA)
Medicinal Chemistry (AREA)
Toxicology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Gastroenterology & Hepatology (AREA)
Wood Science & Technology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Microbiology (AREA)
Biotechnology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Engineering & Computer Science (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

JP58039298A 1982-03-13 1983-03-11 インシユリンへのプレプロインシユリン類似体の変換法 Granted JPS58190398A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19823209184 DE3209184A1 (de)	1982-03-13	1982-03-13	Verfahren zur umwandlung von praeproinsulinanaloga zu insulinen
DE3209184.2		1982-03-13

Publications (2)

Publication Number	Publication Date
JPS58190398A true JPS58190398A (ja)	1983-11-07
JPH0536034B2 JPH0536034B2 (2)	1993-05-28

Family

ID=6158163

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP58039298A Granted JPS58190398A (ja)	1982-03-13	1983-03-11	インシユリンへのプレプロインシユリン類似体の変換法

Country Status (15)

Country	Link
US (1)	US4639333A (2)
EP (1)	EP0089007B1 (2)
JP (1)	JPS58190398A (2)
KR (1)	KR900003502B1 (2)
AT (1)	ATE21118T1 (2)
AU (1)	AU553832B2 (2)
CA (1)	CA1195273A (2)
DE (2)	DE3209184A1 (2)
DK (1)	DK154573C (2)
ES (1)	ES8401448A1 (2)
FI (1)	FI79117C (2)
GR (1)	GR78453B (2)
IE (1)	IE54605B1 (2)
IL (1)	IL68103A (2)
ZA (1)	ZA831693B (2)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3326472A1 (de) *	1983-07-22	1985-02-14	Hoechst Ag, 6230 Frankfurt	Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus
DE3333640A1 (de) *	1983-09-17	1985-04-25	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung von insulin-derivaten, deren b-kette c-terminal verlaengert ist, neue basisch modifizierte insulin-derivate diese enthaltende mittel und ihre verwendung
US4569792A (en) *	1984-06-14	1986-02-11	Eli Lilly And Company	Anti-diabetic compounds
US4569791A (en) *	1984-06-14	1986-02-11	Eli Lilly And Company	Anti-diabetic compounds
US4581165A (en) *	1984-06-14	1986-04-08	Eli Lilly And Company	Anti-diabetic compounds
DK129385A (da) *	1985-03-22	1986-09-23	Novo Industri As	Peptider og fremstilling deraf
DE3880346T2 (de) *	1987-02-25	1993-07-29	Novonordisk As	Insulinderivate.
US5514646A (en) *	1989-02-09	1996-05-07	Chance; Ronald E.	Insulin analogs modified at position 29 of the B chain
CZ283234B6 (cs) *	1990-09-05	1998-02-18	Hoechst Aktiengesellschaft	Enymatický způsob konverse preproinsulinů na insuliny
KR20110059602A (ko)	2008-08-07	2011-06-02	바이오콘 리미티드	인슐린 화합물의 제조방법

Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS55138393A (en) *	1979-04-13	1980-10-29	Shionogi & Co Ltd	Semisynthesis of insulin
JPS56135452A (en) *	1980-02-11	1981-10-22	Novo Industri As	Manufacture of insulin ester
JPS56150051A (en) *	1980-03-27	1981-11-20	Lilly Co Eli	Manufacture of insulin precursor

Family Cites Families (6)

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Publication number	Priority date	Publication date	Assignee	Title
US3276961A (en) *	1963-04-08	1966-10-04	Squibb & Sons Inc	Process for preparing human insulin
GB1426061A (en) *	1972-12-28	1976-02-25	Ici Ltd	Polypeptides
US3903068A (en) *	1972-12-26	1975-09-02	Us Health Education & Welfare	Facile synthesis of human insulin by modification of porcine insulin
NO153061C (no) *	1979-04-13	1986-01-08	Shionogi & Co	Fremgangsmaate for fremstilling av et b30-threonininsulin
DK319780A (da) *	1980-07-24	1982-01-25	Forenede Bryggerier As	Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyren i insuliner
DE3101382A1 (de) *	1981-01-17	1982-09-02	Hoechst Ag, 6000 Frankfurt	"verfahren zur herstellung von humanisulin oder dessen derivaten aus schweineinsulin oder dessen derivaten"

1982
- 1982-03-13 DE DE19823209184 patent/DE3209184A1/de not_active Withdrawn
1983
- 1983-03-10 DE DE8383102337T patent/DE3364838D1/de not_active Expired
- 1983-03-10 FI FI830813A patent/FI79117C/fi not_active IP Right Cessation
- 1983-03-10 AT AT83102337T patent/ATE21118T1/de not_active IP Right Cessation
- 1983-03-10 EP EP83102337A patent/EP0089007B1/de not_active Expired
- 1983-03-10 IL IL68103A patent/IL68103A/xx not_active IP Right Cessation
- 1983-03-11 KR KR1019830000978A patent/KR900003502B1/ko not_active Expired
- 1983-03-11 ES ES520493A patent/ES8401448A1/es not_active Expired
- 1983-03-11 CA CA000423391A patent/CA1195273A/en not_active Expired
- 1983-03-11 JP JP58039298A patent/JPS58190398A/ja active Granted
- 1983-03-11 IE IE529/83A patent/IE54605B1/en not_active IP Right Cessation
- 1983-03-11 AU AU12428/83A patent/AU553832B2/en not_active Ceased
- 1983-03-11 DK DK117883A patent/DK154573C/da not_active IP Right Cessation
- 1983-03-11 GR GR70765A patent/GR78453B/el unknown
- 1983-03-11 ZA ZA831693A patent/ZA831693B/xx unknown
1984
- 1984-10-12 US US06/659,865 patent/US4639333A/en not_active Expired - Lifetime

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS55138393A (en) *	1979-04-13	1980-10-29	Shionogi & Co Ltd	Semisynthesis of insulin
JPS56135452A (en) *	1980-02-11	1981-10-22	Novo Industri As	Manufacture of insulin ester
JPS56150051A (en) *	1980-03-27	1981-11-20	Lilly Co Eli	Manufacture of insulin precursor

Also Published As

Publication number	Publication date
DE3364838D1 (en)	1986-09-04
FI830813A0 (fi)	1983-03-10
IE54605B1 (en)	1989-12-06
ES520493A0 (es)	1983-12-16
FI79117C (fi)	1989-11-10
DK117883A (da)	1983-09-14
IL68103A0 (en)	1983-06-15
IE830529L (en)	1983-09-13
EP0089007A1 (de)	1983-09-21
US4639333A (en)	1987-01-27
DK154573C (da)	1989-05-22
IL68103A (en)	1986-01-31
AU1242883A (en)	1983-09-15
CA1195273A (en)	1985-10-15
ES8401448A1 (es)	1983-12-16
KR900003502B1 (ko)	1990-05-21
ATE21118T1 (de)	1986-08-15
JPH0536034B2 (2)	1993-05-28
DK117883D0 (da)	1983-03-11
FI830813L (fi)	1983-09-14
DE3209184A1 (de)	1983-09-15
FI79117B (fi)	1989-07-31
KR840004169A (ko)	1984-10-10
EP0089007B1 (de)	1986-07-30
AU553832B2 (en)	1986-07-31
GR78453B (2)	1984-09-27
ZA831693B (en)	1983-11-30
DK154573B (da)	1988-11-28

Publication	Publication Date	Title
Yang et al.	2007	Sugar-assisted ligation in glycoprotein synthesis
US4601852A (en)	1986-07-22	Process for the preparation of human or the derivatives thereof from pig insulin or the derivatives thereof
KR100574580B1 (ko)	2006-04-28	정확하게 결합된 시스틴 브릿지를 갖는 인슐린 또는 인슐린유도체를 수득하는 방법
JPS60136596A (ja)	1985-07-20	ペプチド及びこれを有効成分とする利尿剤
EP0020290A1 (de)	1980-12-10	Verfahren zur spezifischen Abspaltung von Proteinsequenzen aus Proteinen
JPS642360B2 (2)	1989-01-17
AU641366B2 (en)	1993-09-23	Peptide compounds
FI79117C (fi)	1989-11-10	Foerfarande foer framstaellning av bovine-, svin- eller humaninsulin.
EP0310887B1 (en)	1993-06-02	Vasoconstrictor peptide
MC2131A1 (fr)	1992-01-03	Nouveaux derives de peptides intestinaux vasoactifs
DK149457B (da)	1986-06-16	Fremgangsmaade til fremstilling af humant insulin eller b30-estere deraf
EP0051205B1 (de)	1986-01-02	Neues Tridekapeptid, Verfahren zu seiner Herstellung und Verwendung
EP0095351B1 (en)	1989-11-08	A precursor of a c-terminal amidated peptide and production thereof
US3988309A (en)	1976-10-26	EEL calcitonin
US3912711A (en)	1975-10-14	Synthetically produced undecapeptide, Substance P
Nokihara et al.	1988	Solid-phase synthesis of porcine cardiodilatin 88
JPS58189149A (ja)	1983-11-04	ヒトインシユリンの半合成方法
DE3876022T2 (de)	1993-04-22	Calcitonin-derivate und deren salze.
EP0367161B1 (de)	1996-06-19	Verfahren zur selektiven Spaltung von Fusionsproteinen
US4058512A (en)	1977-11-15	Synthetic peptides having growth promoting activity
JPS58501208A (ja)	1983-07-28	インシユリン誘導体の製造法
EP0051204A1 (de)	1982-05-12	Neues Dekapeptid, Verfahren zu seiner Herstellung und Verwendung
DE4404168A1 (de)	1995-08-17	Hirudinderivate und Verfahren zu deren Herstellung
Brown et al.	1983	Peptide synthesis. Part 4. Solid-phase syntheses of peptides related to gastrin
Massey et al.	1975	Guinea pig proinsulin. Primary structure of the C-peptide isolated from pancreas