IE914157A1 - Solution phase process for synthesis of peptide - Google Patents

Solution phase process for synthesis of peptide

Info

Publication number: IE914157A1
Authority: IE; Ireland
Prior art keywords: boc; trp; lys; phe; ala
Prior art date: 1990-11-30

Application number

IE415791A

Other languages

English (en)

Original Assignee

Smithkline Beecham Corp

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.)

1990-11-30

Filing date

1991-11-29

Publication date

1992-06-03

1991-11-29 Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp

1992-06-03 Publication of IE914157A1 publication Critical patent/IE914157A1/en

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 16
238000000034 method Methods 0.000 title claims description 31
230000015572 biosynthetic process Effects 0.000 title description 2
238000003786 synthesis reaction Methods 0.000 title 1
238000004519 manufacturing process Methods 0.000 claims abstract description 11
239000007787 solid Substances 0.000 claims description 32
238000005859 coupling reaction Methods 0.000 claims description 27
-1 carbonium ion Chemical class 0.000 claims description 23
230000008878 coupling Effects 0.000 claims description 21
238000010168 coupling process Methods 0.000 claims description 21
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
150000001875 compounds Chemical class 0.000 claims description 16
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 11
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 9
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 8
239000003153 chemical reaction reagent Substances 0.000 claims description 8
239000003054 catalyst Substances 0.000 claims description 7
238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 claims description 6
230000003197 catalytic effect Effects 0.000 claims description 5
239000002516 radical scavenger Substances 0.000 claims description 5
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 4
SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical group CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 9
102000018997 Growth Hormone Human genes 0.000 abstract description 3
108010051696 Growth Hormone Proteins 0.000 abstract description 3
239000000122 growth hormone Substances 0.000 abstract description 3
230000003578 releasing effect Effects 0.000 abstract description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
238000003756 stirring Methods 0.000 description 23
239000000543 intermediate Substances 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
238000004128 high performance liquid chromatography Methods 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000000047 product Substances 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 12
229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 description 12
235000019837 monoammonium phosphate Nutrition 0.000 description 12
239000008367 deionised water Substances 0.000 description 11
229910021641 deionized water Inorganic materials 0.000 description 11
238000005406 washing Methods 0.000 description 11
239000000706 filtrate Substances 0.000 description 10
229910052739 hydrogen Inorganic materials 0.000 description 10
239000001257 hydrogen Substances 0.000 description 10
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
239000000377 silicon dioxide Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
239000000203 mixture Substances 0.000 description 7
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 7
238000000825 ultraviolet detection Methods 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 6
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
230000007935 neutral effect Effects 0.000 description 6
239000000843 powder Substances 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 5
239000005695 Ammonium acetate Substances 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
229940043376 ammonium acetate Drugs 0.000 description 5
235000019257 ammonium acetate Nutrition 0.000 description 5
238000009835 boiling Methods 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000011736 potassium bicarbonate Substances 0.000 description 4
235000015497 potassium bicarbonate Nutrition 0.000 description 4
229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
239000004472 Lysine Substances 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
125000006847 BOC protecting group Chemical group 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 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
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-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
125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
238000010306 acid treatment Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
150000001718 carbodiimides Chemical class 0.000 description 2
229960002885 histidine Drugs 0.000 description 2
229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
239000000463 material Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000004366 reverse phase liquid chromatography Methods 0.000 description 2
AHYFYYVVAXRMKB-QGZVFWFLSA-N (2r)-3-(1h-indol-3-yl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound N([C@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)OCC1=CC=CC=C1 AHYFYYVVAXRMKB-QGZVFWFLSA-N 0.000 description 1
RRONHWAVOYADJL-OAHLLOKOSA-N (2r)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-OAHLLOKOSA-N 0.000 description 1
DYSBKEOCHROEGX-HNNXBMFYSA-N (2s)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(phenylmethoxycarbonylamino)hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 DYSBKEOCHROEGX-HNNXBMFYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 1
JKSIXVZIFHKAPJ-UHFFFAOYSA-N 2h-benzotriazole;hydrate Chemical compound O.C1=CC=C2NN=NC2=C1 JKSIXVZIFHKAPJ-UHFFFAOYSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
229930182832 D-phenylalanine Natural products 0.000 description 1
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 1
125000001711 D-phenylalanine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229930182827 D-tryptophan Natural products 0.000 description 1
125000003941 D-tryptophan group Chemical group [H]C1=C([H])C([H])=C2C(C([C@@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 1
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
206010056438 Growth hormone deficiency Diseases 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
235000019766 L-Lysine Nutrition 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 1
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
229960003767 alanine Drugs 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical group CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000012528 membrane Substances 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000012856 packing Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
239000011148 porous material Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000011282 treatment Methods 0.000 description 1
229960004799 tryptophan Drugs 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-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
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/061—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups
- C07K1/064—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups for omega-amino or -guanidino functions

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Analytical Chemistry (AREA)
Endocrinology (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

IE415791A 1990-11-30 1991-11-29 Solution phase process for synthesis of peptide IE914157A1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US62109490A	1990-11-30	1990-11-30

Publications (1)

Publication Number	Publication Date
IE914157A1 true IE914157A1 (en)	1992-06-03

Family

ID=24488689

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE415791A IE914157A1 (en)	1990-11-30	1991-11-29	Solution phase process for synthesis of peptide

Country Status (10)

Country	Link
EP (1)	EP0564587A4 (fr)
JP (1)	JPH06503578A (fr)
KR (1)	KR930703345A (fr)
AU (1)	AU9166491A (fr)
CA (1)	CA2097305A1 (fr)
IE (1)	IE914157A1 (fr)
MX (1)	MX9102333A (fr)
PT (1)	PT99654A (fr)
WO (1)	WO1992009620A1 (fr)
ZA (1)	ZA919440B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3480848B2 (ja) *	1992-06-19	2003-12-22	タカラバイオ株式会社	環状ペプチドの合成方法
GB0814519D0 (en) *	2008-08-08	2008-09-17	Imp Innovations Ltd	Process

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4411890A (en) *	1981-04-14	1983-10-25	Beckman Instruments, Inc.	Synthetic peptides having pituitary growth hormone releasing activity
US4105652A (en) *	1977-08-05	1978-08-08	Hoffmann-La Roche Inc.	Synthesis of human β-endorphin
US4237046A (en) *	1979-04-27	1980-12-02	Miklos Bodanszky	Polypeptides and methods of preparation
WO1992001709A1 (fr) *	1990-07-24	1992-02-06	Eastman Kodak Company	Procede de synthese de peptides

1991
- 1991-11-25 JP JP4503322A patent/JPH06503578A/ja active Pending
- 1991-11-25 KR KR1019930701616A patent/KR930703345A/ko not_active Withdrawn
- 1991-11-25 AU AU91664/91A patent/AU9166491A/en not_active Abandoned
- 1991-11-25 CA CA002097305A patent/CA2097305A1/fr not_active Abandoned
- 1991-11-25 WO PCT/US1991/008863 patent/WO1992009620A1/fr not_active Ceased
- 1991-11-25 EP EP9292903706A patent/EP0564587A4/en not_active Withdrawn
- 1991-11-29 IE IE415791A patent/IE914157A1/en not_active Application Discontinuation
- 1991-11-29 PT PT99654A patent/PT99654A/pt not_active Application Discontinuation
- 1991-11-29 ZA ZA919440A patent/ZA919440B/xx unknown
- 1991-12-02 MX MX9102333A patent/MX9102333A/es unknown

Also Published As

Publication number	Publication date
AU9166491A (en)	1992-06-25
JPH06503578A (ja)	1994-04-21
ZA919440B (en)	1992-12-30
CA2097305A1 (fr)	1992-05-31
EP0564587A4 (en)	1994-08-24
MX9102333A (es)	1993-06-01
EP0564587A1 (fr)	1993-10-13
KR930703345A (ko)	1993-11-29
PT99654A (pt)	1992-10-30
WO1992009620A1 (fr)	1992-06-11

Legal Events

Date	Code	Title	Description
2003-02-05	FC9A	Application refused sect. 31(1)

Publication	Publication Date	Title
Brady et al.	1987	Large-scale synthesis of a cyclic hexapeptide analog of somatostatin
JP5850458B2 (ja)	2016-02-03	デガレリックスの製造方法
EP3708576B1 (fr)	2023-02-22	Procédé de préparation d'amg 416
US6235876B1 (en)	2001-05-22	Liquid phase process for the preparation of GNRH peptides
WO2001019849A1 (fr)	2001-03-22	Procede de preparation de h-tyr-d-ala-phe(f)-phe-nh¿2?
Li et al.	1960	The Synthesis of L-Histidyl-L-phenylalanyl-L-ornithyl-L-tryptophyl-glycine and L-Histidyl-D-phenylalanyl-L-ornithyl-L-tryptophyl-glycine and their Melanocyte-stimulating Activity
Müller et al.	1999	Synthesis of N‐carboxyalkyl and N‐aminoalkyl functionalized dipeptide building units for the assembly of backbone cyclic peptides
US5712367A (en)	1998-01-27	Process for the solubilization of peptides and process for peptide synthesis
CN120271660A (zh)	2025-07-08	一种高效选择性拮抗剂bq-788的制备方法
IE914157A1 (en)	1992-06-03	Solution phase process for synthesis of peptide
EP1654280B1 (fr)	2008-05-07	Preparation de peptides somatostatine
KR100203548B1 (ko)	1999-06-15	고체상 합성에 의한 펩티드의 제조방법
CN117003791B (zh)	2025-06-27	一种二苯基膦酰氧基双酚a类化合物及其制备美白九肽-1中的应用
KR100591832B1 (ko)	2006-06-20	트립토판 잔기를 갖는 펩티드의 합성공정
Klausner et al.	1977	Crown ethers as catalysts of fluoride-anion-mediated reactions in peptide synthesis. Part 1. Protection of tryptophan by benzyloxycarbonyl and 2, 4-dichlorobenzyloxycarbonyl groups
EP1062231A1 (fr)	2000-12-27	Procede de preparation d'un tetrapeptide
JPH049800B2 (fr)	1992-02-21
JP2927978B2 (ja)	1999-07-28	Ｌｈ−ｒｈ類似体の一時的最小保護合成法
RU2111972C1 (ru)	1998-05-27	СПОСОБ ПОЛУЧЕНИЯ ПЕПТИДА δ СНА
EP0106282A2 (fr)	1984-04-25	Préparation d'un intermédiaire de la caéruléine
RU2111215C1 (ru)	1998-05-20	СПОСОБ ПОЛУЧЕНИЯ ПЕПТИДА δ- СНА
Reissmann	1999	B. MuÈ ller D. Besser P. KleinwaÈchter O. Arad
JPH07316193A (ja)	1995-12-05	ペプチド誘導体およびその用途
Tesser et al.	1971	Synthesis and biological activity of four analogues of β‐corticotropin
Swart et al.	1986	Solid phase synthesis of a growth hormone releasing factor Tyr-D-Trp-Ala-Trp-D-Phe-NH2