NL8201650A - Semisynthetische bereiding van humane insuline. - Google Patents

Semisynthetische bereiding van humane insuline. Download PDF

Info

Publication number: NL8201650A
Authority: NL; Netherlands
Prior art keywords: insulin; human insulin; amino acid; ester; coupling
Prior art date: 1982-04-21

Application number

NL8201650A

Other languages

English (en)

Dutch (nl)

Original Assignee

Akzo Nv

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.)

1982-04-21

Filing date

1982-04-21

Publication date

1983-11-16

1982-04-21 Application filed by Akzo Nv filed Critical Akzo Nv

1982-04-21 Priority to NL8201650A priority Critical patent/NL8201650A/nl

1983-04-13 Priority to DK198301616A priority patent/DK173007B1/da

1983-04-13 Priority to ZA832602A priority patent/ZA832602B/xx

1983-04-14 Priority to AT83200530T priority patent/ATE42203T1/de

1983-04-14 Priority to IL68397A priority patent/IL68397A/xx

1983-04-14 Priority to DE8383200530T priority patent/DE3379640D1/de

1983-04-14 Priority to EP83200530A priority patent/EP0092280B1/fr

1983-04-15 Priority to AU13554/83A priority patent/AU554050B2/en

1983-04-20 Priority to CA000426236A priority patent/CA1202587A/fr

1983-04-20 Priority to PL1983241575A priority patent/PL143571B1/pl

1983-04-20 Priority to JP58069862A priority patent/JPS58189149A/ja

1983-04-20 Priority to SU833582755A priority patent/SU1232148A3/ru

1983-04-20 Priority to ES521674A priority patent/ES521674A0/es

1983-04-21 Priority to HU831392A priority patent/HU189268B/hu

1983-11-16 Publication of NL8201650A publication Critical patent/NL8201650A/nl

1985-08-20 Priority to US06/767,481 priority patent/US4840897A/en

1992-10-28 Priority to JP4290556A priority patent/JPH0735399B2/ja

Links

238000002360 preparation method Methods 0.000 title claims abstract description 8
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 61
102000004877 Insulin Human genes 0.000 title claims description 30
108090001061 Insulin Proteins 0.000 title claims description 30
229940125396 insulin Drugs 0.000 title claims description 28
150000001413 amino acids Chemical class 0.000 claims abstract description 31
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 claims abstract description 20
101000976075 Homo sapiens Insulin Proteins 0.000 claims abstract description 18
235000000346 sugar Nutrition 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims abstract description 13
150000002148 esters Chemical class 0.000 claims abstract description 9
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 8
230000002255 enzymatic effect Effects 0.000 claims abstract description 5
150000001408 amides Chemical class 0.000 claims abstract description 4
238000005859 coupling reaction Methods 0.000 claims description 23
230000008878 coupling Effects 0.000 claims description 22
238000010168 coupling process Methods 0.000 claims description 22
150000003587 threonine derivatives Chemical class 0.000 claims description 8
102000000496 Carboxypeptidases A Human genes 0.000 claims description 6
108010080937 Carboxypeptidases A Proteins 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 6
102000005367 Carboxypeptidases Human genes 0.000 claims description 5
108010006303 Carboxypeptidases Proteins 0.000 claims description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 5
238000003776 cleavage reaction Methods 0.000 claims description 4
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
230000007017 scission Effects 0.000 claims description 4
150000001875 compounds Chemical class 0.000 claims 2
235000001014 amino acid Nutrition 0.000 description 27
239000000047 product Substances 0.000 description 13
102000004190 Enzymes Human genes 0.000 description 10
108090000790 Enzymes Proteins 0.000 description 10
229940088598 enzyme Drugs 0.000 description 10
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 7
239000004473 Threonine Substances 0.000 description 7
108090000631 Trypsin Proteins 0.000 description 7
102000004142 Trypsin Human genes 0.000 description 7
238000000926 separation method Methods 0.000 description 7
239000012588 trypsin Substances 0.000 description 7
230000002209 hydrophobic effect Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
101000993800 Sus scrofa Insulin Proteins 0.000 description 4
239000000872 buffer Substances 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000000758 substrate Substances 0.000 description 4
102000003670 Carboxypeptidase B Human genes 0.000 description 3
108090000087 Carboxypeptidase B Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
239000004475 Arginine Substances 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
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 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
102000035195 Peptidases Human genes 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
VEIKMWOMUYMMMK-FCLVOEFKSA-N Thr-Phe-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 VEIKMWOMUYMMMK-FCLVOEFKSA-N 0.000 description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000000890 antigenic effect Effects 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000004026 insulin derivative Substances 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
239000000203 mixture Substances 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-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
241000590035 Achromobacter lyticus Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
102000018389 Exopeptidases Human genes 0.000 description 1
108010091443 Exopeptidases Proteins 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
102000002464 Galactosidases Human genes 0.000 description 1
108010093031 Galactosidases Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
108010053229 Lysyl endopeptidase Proteins 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
108090000279 Peptidyltransferases Proteins 0.000 description 1
GKZIWHRNKRBEOH-HOTGVXAUSA-N Phe-Phe Chemical compound C([C@H]([NH3+])C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)C1=CC=CC=C1 GKZIWHRNKRBEOH-HOTGVXAUSA-N 0.000 description 1
108010005991 Pork Regular Insulin Proteins 0.000 description 1
108010076181 Proinsulin Proteins 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
IQHUITKNHOKGFC-MIMYLULJSA-N Thr-Phe Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IQHUITKNHOKGFC-MIMYLULJSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000002009 allergenic effect Effects 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
-1 aromatic amino acids Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000007857 degradation product Substances 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
150000002337 glycosamines Chemical class 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000001810 trypsinlike Effects 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 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
- 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
- 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)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Zoology (AREA)
Genetics & Genomics (AREA)
Gastroenterology & Hepatology (AREA)
Endocrinology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Toxicology (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

NL8201650A 1982-04-21 1982-04-21 Semisynthetische bereiding van humane insuline. NL8201650A (nl)

Priority Applications (16)

Application Number	Priority Date	Filing Date	Title
NL8201650A NL8201650A (nl)	1982-04-21	1982-04-21	Semisynthetische bereiding van humane insuline.
DK198301616A DK173007B1 (da)	1982-04-21	1983-04-13	Fremgangsmåde til semisyntetisk fremstilling af humaninsulin og modificeret humaninsulin til brug ved fremgangsmåden
ZA832602A ZA832602B (en)	1982-04-21	1983-04-13	Semi-synthetic preparation of human insulin
AT83200530T ATE42203T1 (de)	1982-04-21	1983-04-14	Semi-synthetisches verfahren zur herstellung von insulin.
IL68397A IL68397A (en)	1982-04-21	1983-04-14	Semi-synthetic preparation of human insulin and a modified human insulin
DE8383200530T DE3379640D1 (en)	1982-04-21	1983-04-14	Semi-synthetic preparation of human insulin
EP83200530A EP0092280B1 (fr)	1982-04-21	1983-04-14	Procédé semi-synthétique de préparation de l'insuline
AU13554/83A AU554050B2 (en)	1982-04-21	1983-04-15	Semi-synthetic preparation of human insulin 0
CA000426236A CA1202587A (fr)	1982-04-21	1983-04-20	Preparation semi-synthetique d'insuline humaine
PL1983241575A PL143571B1 (en)	1982-04-21	1983-04-20	Method of obtaining semi-synthetic human insulin
JP58069862A JPS58189149A (ja)	1982-04-21	1983-04-20	ヒトインシユリンの半合成方法
SU833582755A SU1232148A3 (ru)	1982-04-21	1983-04-20	Способ получени инсулина человека
ES521674A ES521674A0 (es)	1982-04-21	1983-04-20	Metodo para la preparacion de insulina humana semisintetica.
HU831392A HU189268B (en)	1982-04-21	1983-04-21	Process for the semisynthetic preparation of humane insuline
US06/767,481 US4840897A (en)	1982-04-21	1985-08-20	Modified human insulin and its use as starting material for the preparation of human insulin
JP4290556A JPH0735399B2 (ja)	1982-04-21	1992-10-28	変性ヒトインシュリン

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
NL8201650A NL8201650A (nl)	1982-04-21	1982-04-21	Semisynthetische bereiding van humane insuline.
NL8201650		1982-04-21

Publications (1)

Publication Number	Publication Date
NL8201650A true NL8201650A (nl)	1983-11-16

Family

ID=19839621

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8201650A NL8201650A (nl)	1982-04-21	1982-04-21	Semisynthetische bereiding van humane insuline.

Country Status (15)

Country	Link
US (1)	US4840897A (fr)
EP (1)	EP0092280B1 (fr)
JP (2)	JPS58189149A (fr)
AT (1)	ATE42203T1 (fr)
AU (1)	AU554050B2 (fr)
CA (1)	CA1202587A (fr)
DE (1)	DE3379640D1 (fr)
DK (1)	DK173007B1 (fr)
ES (1)	ES521674A0 (fr)
HU (1)	HU189268B (fr)
IL (1)	IL68397A (fr)
NL (1)	NL8201650A (fr)
PL (1)	PL143571B1 (fr)
SU (1)	SU1232148A3 (fr)
ZA (1)	ZA832602B (fr)

Families Citing this family (7)

* 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
DE3326473A1 (de) *	1983-07-22	1985-01-31	Hoechst Ag, 6230 Frankfurt	Pharmazeutisches mittel zur behandlung des diabetes mellitus
DE3327709A1 (de) *	1983-07-29	1985-02-07	Hoechst Ag, 6230 Frankfurt	Insulin-derivat-kristallsuspensionen, verfahren zu deren herstellung und deren verwendung
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
DK309184D0 (da) *	1984-06-25	1984-06-25	Nordisk Insulinlab	Fremgangsmaade til isolering af insulin eller insulinlignende materiale fra en fermenteringsvaeske
NZ273285A (en) *	1993-09-17	1997-10-24	Novo Nordisk As	Insulin derivatives and compositions thereof
CN113956326B (zh) *	2021-09-15	2024-05-28	河南工业大学	一种短肽单体，结构自愈型肽基水凝胶及其应用

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3276961A (en) *	1963-04-08	1966-10-04	Squibb & Sons Inc	Process for preparing human insulin
US4182654A (en) *	1974-09-18	1980-01-08	Pierce Chemical Company	Production of polypeptides using polynucleotides
JPS55138393A (en) *	1979-04-13	1980-10-29	Shionogi & Co Ltd	Semisynthesis of insulin
NO153061C (no) *	1979-04-13	1986-01-08	Shionogi & Co	Fremgangsmaate for fremstilling av et b30-threonininsulin
JPS55138391A (en) *	1979-04-13	1980-10-29	Shionogi & Co Ltd	New synthetic method of peptide derivative
DK147437A (en) *	1980-02-11	1900-01-01		Process for preparing human insulin or threonine B30 esters of human insulin, or a salt or complex thereof
IE50892B1 (en) *	1980-02-11	1986-08-06	Novo Industri As	Process for preparing insulin esters
DK319780A (da) *	1980-07-24	1982-01-25	Forenede Bryggerier As	Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyren i insuliner
DE3327928A1 (de) *	1983-08-03	1985-02-21	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung von insulin-derivaten

1982
- 1982-04-21 NL NL8201650A patent/NL8201650A/nl not_active Application Discontinuation
1983
- 1983-04-13 DK DK198301616A patent/DK173007B1/da not_active IP Right Cessation
- 1983-04-13 ZA ZA832602A patent/ZA832602B/xx unknown
- 1983-04-14 IL IL68397A patent/IL68397A/xx not_active IP Right Cessation
- 1983-04-14 EP EP83200530A patent/EP0092280B1/fr not_active Expired
- 1983-04-14 AT AT83200530T patent/ATE42203T1/de not_active IP Right Cessation
- 1983-04-14 DE DE8383200530T patent/DE3379640D1/de not_active Expired
- 1983-04-15 AU AU13554/83A patent/AU554050B2/en not_active Expired
- 1983-04-20 PL PL1983241575A patent/PL143571B1/pl unknown
- 1983-04-20 CA CA000426236A patent/CA1202587A/fr not_active Expired
- 1983-04-20 ES ES521674A patent/ES521674A0/es active Granted
- 1983-04-20 SU SU833582755A patent/SU1232148A3/ru active
- 1983-04-20 JP JP58069862A patent/JPS58189149A/ja active Granted
- 1983-04-21 HU HU831392A patent/HU189268B/hu unknown
1985
- 1985-08-20 US US06/767,481 patent/US4840897A/en not_active Expired - Lifetime
1992
- 1992-10-28 JP JP4290556A patent/JPH0735399B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
JPH0533993B2 (fr)	1993-05-20
HU189268B (en)	1986-06-30
US4840897A (en)	1989-06-20
SU1232148A3 (ru)	1986-05-15
DE3379640D1 (en)	1989-05-24
AU1355483A (en)	1983-10-27
DK161683A (da)	1983-10-22
DK173007B1 (da)	1999-11-08
ES8405760A1 (es)	1984-06-16
ATE42203T1 (de)	1989-05-15
DK161683D0 (da)	1983-04-13
JPH05339290A (ja)	1993-12-21
JPH0735399B2 (ja)	1995-04-19
PL241575A1 (en)	1983-12-19
ZA832602B (en)	1984-01-25
IL68397A0 (en)	1983-07-31
CA1202587A (fr)	1986-04-01
EP0092280B1 (fr)	1989-04-19
ES521674A0 (es)	1984-06-16
PL143571B1 (en)	1988-02-29
JPS58189149A (ja)	1983-11-04
IL68397A (en)	1986-01-31
EP0092280A1 (fr)	1983-10-26
AU554050B2 (en)	1986-08-07

Legal Events

Date	Code	Title
1983-11-16	A1B	A search report has been drawn up
1985-01-01	A85	Still pending on 85-01-01
1985-12-02	BV	The patent application has lapsed

Publication	Publication Date	Title
US4320196A (en)	1982-03-16	Semi-synthesis of human insulin
Kimmel	1967	[70] Guanidination of proteins
Nitecki et al.	1966	Immunochemical studies on the poly-γ-D-glutamyl capsule of Bacillus anthracis. II. The synthesis of eight dipeptides and four tripeptides of glutamic acid
Grant et al.	1959	Studies on the collagenases of Clostridium histolyticum
MARKUSSEN et al.	1985	Single chain des‐(B30) insulin: intramolecular crosslinking of insulin by trypsin catalyzed transpeptidation
KR19980064213A (ko)	1998-10-07	고압 액체 크로마토그래피에 의한 인슐린 분리 방법
Rose et al.	1991	Preparation of well-defined protein conjugates using enzyme-assisted reverse proteolysis
KR20050044855A (ko)	2005-05-13	인슐린 화합물의 제조 방법
EP0017938B1 (fr)	1983-08-03	Procédé de préparation de la B30-thréonine insuline
US4320197A (en)	1982-03-16	Semi-synthesis of human insulin
US4639332A (en)	1987-01-27	Process for the preparation of insulin derivatives
JP2001526026A (ja)	2001-12-18	タイセイヨウサケ由来の孵化液の抽出方法および使用
EP0092280B1 (fr)	1989-04-19	Procédé semi-synthétique de préparation de l'insuline
OZAWA	1967	Bridging Reagent for Protein I. The Reaction of Diisocyanates with Lysine and Enzyme Proteins
EP0088117B1 (fr)	1986-09-24	Procede de preparation d'insuline humaine ou de ses esters b-30
JPH0536034B2 (fr)	1993-05-28
Goldberger	1967	[34] Trifluoroacetylation of ϵ-amino groups
Yamasaki et al.	1975	Studies on the common active site of growth hormone. Revision of the amino acid sequence of an active fragment of bovine growth hormone.
JPH03503958A (ja)	1991-09-05	カルシトニン遺伝子関連ペプチドの製造方法
JPH01160496A (ja)	1989-06-23	融合タンパク質の選択的分解方法
EP0087238A1 (fr)	1983-08-31	Méthode de préparation d'insuline humaine à partir d'insuline non-humaine-
Koryakina et al.	1985	Determination of the cystine and cysteine contents of proteins with the aid of an amino acid analyzer
JPH02257890A (ja)	1990-10-18	ペプチドアミドの製造方法
JPS6246560B2 (fr)	1987-10-02
FR2607137A1 (fr)	1988-05-27	Procede d'isolation de protides biologiquement actifs, stables en milieu acide