DE69732640T2 - Festphasen-peptidsynthese - Google Patents
Festphasen-peptidsynthese Download PDFInfo
- Publication number
- DE69732640T2 DE69732640T2 DE69732640T DE69732640T DE69732640T2 DE 69732640 T2 DE69732640 T2 DE 69732640T2 DE 69732640 T DE69732640 T DE 69732640T DE 69732640 T DE69732640 T DE 69732640T DE 69732640 T2 DE69732640 T2 DE 69732640T2
- Authority
- DE
- Germany
- Prior art keywords
- peptide
- acid
- protected
- sequence
- fmoc
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000010647 peptide synthesis reaction Methods 0.000 title abstract description 21
- 239000007790 solid phase Substances 0.000 title abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 137
- 238000000034 method Methods 0.000 claims abstract description 77
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 51
- 238000010532 solid phase synthesis reaction Methods 0.000 claims abstract description 8
- 239000011347 resin Substances 0.000 claims description 100
- 229920005989 resin Polymers 0.000 claims description 100
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 99
- -1 4-methoxy-2,3,6-trimethylphenylsulfonyl Chemical group 0.000 claims description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- 150000001413 amino acids Chemical class 0.000 claims description 66
- 230000015572 biosynthetic process Effects 0.000 claims description 66
- 238000003786 synthesis reaction Methods 0.000 claims description 63
- 238000010168 coupling process Methods 0.000 claims description 45
- 238000005859 coupling reaction Methods 0.000 claims description 45
- 230000008878 coupling Effects 0.000 claims description 43
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 42
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 40
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- 150000008064 anhydrides Chemical class 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 14
- VUCNQOPCYRJCGQ-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenoxy]acetic acid Chemical compound OCC1=CC=C(OCC(O)=O)C=C1 VUCNQOPCYRJCGQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 239000004698 Polyethylene Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 229920000573 polyethylene Polymers 0.000 claims description 9
- HXOYWJCDYVODON-UHFFFAOYSA-N 4-[4-(hydroxymethyl)-3-methoxyphenoxy]butanoic acid Chemical compound COC1=CC(OCCCC(O)=O)=CC=C1CO HXOYWJCDYVODON-UHFFFAOYSA-N 0.000 claims description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 102000007079 Peptide Fragments Human genes 0.000 claims description 6
- 108010033276 Peptide Fragments Proteins 0.000 claims description 6
- 239000012317 TBTU Substances 0.000 claims description 6
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 6
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 239000012634 fragment Substances 0.000 claims description 6
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 239000004793 Polystyrene Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 229920002223 polystyrene Polymers 0.000 claims description 5
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 4
- 229920002401 polyacrylamide Polymers 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- RWQUWTMOHXGTNN-UHFFFAOYSA-N 9-n,10-n-bis(4-butylphenyl)-9-n,10-n-bis(4-methylphenyl)phenanthrene-9,10-diamine Chemical compound C1=CC(CCCC)=CC=C1N(C=1C2=CC=CC=C2C2=CC=CC=C2C=1N(C=1C=CC(C)=CC=1)C=1C=CC(CCCC)=CC=1)C1=CC=C(C)C=C1 RWQUWTMOHXGTNN-UHFFFAOYSA-N 0.000 claims description 3
- 239000007821 HATU Substances 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 150000004703 alkoxides Chemical class 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 150000001718 carbodiimides Chemical class 0.000 claims description 3
- 125000005518 carboxamido group Chemical group 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- QEHRETCJMLQPCR-UHFFFAOYSA-N (2,4-dimethoxyphenyl)-(4-hydroxyphenyl)methanone Chemical compound COC1=CC(OC)=CC=C1C(=O)C1=CC=C(O)C=C1 QEHRETCJMLQPCR-UHFFFAOYSA-N 0.000 claims description 2
- KODNUMJIUACFIE-UHFFFAOYSA-N 2-amino-1-[carbamohydrazonoyl(hydroxy)amino]sulfanyl-1-hydroxyguanidine Chemical compound NN=C(N)N(O)SN(O)C(N)=NN KODNUMJIUACFIE-UHFFFAOYSA-N 0.000 claims description 2
- 102000005367 Carboxypeptidases Human genes 0.000 claims description 2
- 108010006303 Carboxypeptidases Proteins 0.000 claims description 2
- 102000005593 Endopeptidases Human genes 0.000 claims description 2
- 108010059378 Endopeptidases Proteins 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 102000004190 Enzymes Human genes 0.000 claims description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 150000001805 chlorine compounds Chemical class 0.000 claims description 2
- 229940066758 endopeptidases Drugs 0.000 claims description 2
- 229940088598 enzyme Drugs 0.000 claims description 2
- 150000002222 fluorine compounds Chemical class 0.000 claims description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 229920000126 latex Polymers 0.000 claims description 2
- 239000004816 latex Substances 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 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 claims description 2
- 239000002243 precursor Substances 0.000 claims 13
- IMMCAKJISYGPDQ-UHFFFAOYSA-N 1-chloro-9,10-bis(phenylethynyl)anthracene Chemical compound C12=CC=CC=C2C(C#CC=2C=CC=CC=2)=C2C(Cl)=CC=CC2=C1C#CC1=CC=CC=C1 IMMCAKJISYGPDQ-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 58
- 238000004128 high performance liquid chromatography Methods 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 238000012217 deletion Methods 0.000 description 34
- 230000037430 deletion Effects 0.000 description 34
- 230000010933 acylation Effects 0.000 description 24
- 238000005917 acylation reaction Methods 0.000 description 24
- 238000012360 testing method Methods 0.000 description 24
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 239000003153 chemical reaction reagent Substances 0.000 description 21
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 20
- 238000005406 washing Methods 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 125000005647 linker group Chemical group 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 15
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 14
- 238000010511 deprotection reaction Methods 0.000 description 13
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 11
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 11
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 11
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- VVQIIIAZJXTLRE-QMMMGPOBSA-N (2s)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](N)C(O)=O VVQIIIAZJXTLRE-QMMMGPOBSA-N 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 8
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- VXGABWCSZZWXPC-UHFFFAOYSA-N methyl 2-(methylamino)acetate Chemical compound CNCC(=O)OC VXGABWCSZZWXPC-UHFFFAOYSA-N 0.000 description 8
- 239000004743 Polypropylene Substances 0.000 description 7
- 235000004279 alanine Nutrition 0.000 description 7
- 229920001155 polypropylene Polymers 0.000 description 7
- OBUGXZVDQXDGTF-VEJNRXSDSA-N (3s)-3-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]-4-[[(2s)-1-[[(2s,3s)-1-[[(2s)-4-amino-1-(carboxymethylamino)-1,4-dioxobutan-2-yl]am Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 OBUGXZVDQXDGTF-VEJNRXSDSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- ITECRQOOEQWFPE-UHFFFAOYSA-N 2-hydroxy-2-(4-methoxyphenyl)acetic acid Chemical compound COC1=CC=C(C(O)C(O)=O)C=C1 ITECRQOOEQWFPE-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 229920000361 Poly(styrene)-block-poly(ethylene glycol) Polymers 0.000 description 5
- 108700041474 des(formylvalyl)gramicidin Proteins 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- QPJSUIGXIBEQAC-UHFFFAOYSA-N n-(2,4-dichloro-5-propan-2-yloxyphenyl)acetamide Chemical compound CC(C)OC1=CC(NC(C)=O)=C(Cl)C=C1Cl QPJSUIGXIBEQAC-UHFFFAOYSA-N 0.000 description 4
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 4
- 108010054442 polyalanine Proteins 0.000 description 4
- 108700027361 sarcosine methyl ester Proteins 0.000 description 4
- HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 239000004952 Polyamide Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002669 lysines Chemical class 0.000 description 3
- 230000007030 peptide scission Effects 0.000 description 3
- 229920002647 polyamide Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 description 2
- WPWKJUVXEMKOHS-UHFFFAOYSA-N 3-[4-(hydroxymethyl)phenoxy]propanoic acid Chemical compound OCC1=CC=C(OCCC(O)=O)C=C1 WPWKJUVXEMKOHS-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 241000024188 Andala Species 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001295 alanines Chemical class 0.000 description 2
- 230000006229 amino acid addition Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010265 fast atom bombardment Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 1
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
- ZNJRONVKWRHYBF-UHFFFAOYSA-N 2-[2-[2-(1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-7-yl)ethenyl]-6-methylpyran-4-ylidene]propanedinitrile Chemical compound O1C(C)=CC(=C(C#N)C#N)C=C1C=CC1=CC(CCCN2CCC3)=C2C3=C1 ZNJRONVKWRHYBF-UHFFFAOYSA-N 0.000 description 1
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108010092674 Enkephalins Proteins 0.000 description 1
- BBBXWRGITSUJPB-YUMQZZPRSA-N Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O BBBXWRGITSUJPB-YUMQZZPRSA-N 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 241000209027 Ilex aquifolium Species 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 229920001367 Merrifield resin Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003196 chaotropic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005112 continuous flow technique Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 150000002463 imidates Chemical class 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
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- URLZCHNOLZSCCA-UHFFFAOYSA-N leu-enkephalin Chemical group C=1C=C(O)C=CC=1CC(N)C(=O)NCC(=O)NCC(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=CC=C1 URLZCHNOLZSCCA-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- JPDSHWJXMMBSTD-UHFFFAOYSA-N methyl 3-nitro-4-sulfanylbenzoate Chemical compound COC(=O)C1=CC=C(S)C([N+]([O-])=O)=C1 JPDSHWJXMMBSTD-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000012607 strong cation exchange resin Substances 0.000 description 1
- 230000006918 subunit interaction Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
- C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
-
- 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
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Prostheses (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK97196 | 1996-09-09 | ||
| DK97196 | 1996-09-09 | ||
| PCT/DK1997/000375 WO1998011125A1 (en) | 1996-09-09 | 1997-09-09 | Improved solid-phase peptide synthesis and agent for use in such synthesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69732640D1 DE69732640D1 (de) | 2005-04-07 |
| DE69732640T2 true DE69732640T2 (de) | 2006-01-12 |
Family
ID=8099561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69732640T Expired - Lifetime DE69732640T2 (de) | 1996-09-09 | 1997-09-09 | Festphasen-peptidsynthese |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7348404B2 (enExample) |
| EP (1) | EP0929567B1 (enExample) |
| JP (1) | JP4405594B2 (enExample) |
| AT (1) | ATE290014T1 (enExample) |
| AU (1) | AU723268B2 (enExample) |
| CA (1) | CA2265900C (enExample) |
| CZ (1) | CZ295838B6 (enExample) |
| DE (1) | DE69732640T2 (enExample) |
| DK (1) | DK0929567T3 (enExample) |
| ES (1) | ES2239364T3 (enExample) |
| HU (1) | HU230354B1 (enExample) |
| IL (1) | IL128829A (enExample) |
| PT (1) | PT929567E (enExample) |
| WO (1) | WO1998011125A1 (enExample) |
Families Citing this family (102)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL138214A0 (en) * | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
| US7550425B2 (en) | 2000-06-16 | 2009-06-23 | Zealand Pharma A/S | Diuretic peptide conjugates |
| WO2006045503A1 (en) | 2004-10-19 | 2006-05-04 | Lonza Ag | Method for solid phase peptide synthesis |
| AU2006242998B2 (en) | 2005-05-04 | 2012-03-22 | Zealand Pharma A/S | Glucagon-like-peptide-2 (GLP-2) analogues |
| GB0514071D0 (en) | 2005-07-07 | 2005-08-17 | Zealand Pharma As | N- or C- terminally modified small peptides |
| JPWO2007060860A1 (ja) * | 2005-11-22 | 2009-05-07 | 学校法人日本大学 | ピロールイミダゾールポリアミドの固相自動合成 |
| CN101336229B (zh) | 2005-12-23 | 2012-06-13 | 西兰岛药物有限公司 | 改性的拟赖氨酸化合物 |
| EP1991560B1 (en) * | 2006-02-20 | 2018-04-04 | Ewha University-Industry Collaboration Foundation | Peptide having cell membrane penetrating activity |
| CA2647867C (en) * | 2006-03-29 | 2015-11-03 | Otsuka Chemical Co., Ltd. | Method for production of peptide thioester compound |
| EP2051995B1 (en) | 2006-11-08 | 2017-02-08 | Zealand Pharma A/S | Selective glucagon-like-peptide-2 (glp-2) analogues |
| EP2158214B1 (en) | 2007-06-15 | 2011-08-17 | Zealand Pharma A/S | Glucagon analogues |
| JP5635530B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| DK2370461T3 (da) | 2008-12-15 | 2013-12-16 | Zealand Pharma As | Glucagonanaloger |
| BRPI0823377A2 (pt) | 2008-12-15 | 2016-09-27 | Zealand Pharma As | análogos de glucagon |
| MA32970B1 (fr) | 2008-12-15 | 2012-01-02 | Zealand Pharma As | Analogues du glucagon |
| JP6054742B2 (ja) | 2009-07-13 | 2016-12-27 | ジーランド ファーマ アクティーゼルスカブ | アシル化グルカゴン類似体 |
| JP5969461B2 (ja) | 2010-04-27 | 2016-08-17 | ジーランド ファーマ アクティーゼルスカブ | Ｇｌｐ−１受容体作動薬とガストリンとのペプチド複合体及びその使用 |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| US9169310B2 (en) | 2010-06-24 | 2015-10-27 | Zealand Pharma A/S | Glucagon analogues |
| PH12013501495A1 (en) | 2011-01-20 | 2013-09-16 | Zealand Pharma As | Combination of acylated glucagon analogues with insulin analogues |
| CN104144704B (zh) | 2011-11-03 | 2018-03-23 | 西兰制药公司 | Glp‑1受体激动剂肽胃泌素缀合物 |
| SG11201403377QA (en) | 2011-12-23 | 2014-07-30 | Zealand Pharma As | Glucagon analogues |
| WO2013098408A1 (en) | 2011-12-30 | 2013-07-04 | Zealand Pharma A/S | Glucagon and cck receptor agonist peptide conjugates |
| TW201336864A (zh) | 2012-02-03 | 2013-09-16 | Zealand Pharma As | 胃飢餓素（ｇｈｒｅｌｉｎ）類似物 |
| EP2844670B1 (en) | 2012-05-03 | 2017-12-06 | Zealand Pharma A/S | Glucagon-like-peptide-2 (glp-2) analogues |
| JP6228187B2 (ja) | 2012-05-03 | 2017-11-08 | ジーランド ファーマ アクティーゼルスカブ | Ｇｉｐ−ｇｌｐ−１デュアルアゴニスト化合物及び方法 |
| MX356957B (es) | 2012-07-23 | 2018-06-20 | Zealand Pharma As | Analogos del glucagon. |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| CN105051067B (zh) | 2013-03-12 | 2020-04-17 | 分子模板公司 | 用于引起细胞内化的cd20结合免疫毒素及其使用方法 |
| US9169287B2 (en) | 2013-03-15 | 2015-10-27 | Massachusetts Institute Of Technology | Solid phase peptide synthesis processes and associated systems |
| US9695214B2 (en) | 2013-03-15 | 2017-07-04 | Massachusetts Institute Of Technology | Solid phase peptide synthesis processes and associated systems |
| DK2976325T3 (en) | 2013-03-21 | 2017-06-06 | Sanofi Aventis Deutschland | SYNTHESIS OF PEPTIDE PRODUCTS CONTAINING CYCLIC IMID |
| AU2014234400B2 (en) | 2013-03-21 | 2017-11-16 | Sanofi-Aventis Deutschland Gmbh | Synthesis of hydantoin containing peptide products |
| CA2926314C (en) | 2013-10-17 | 2023-08-29 | Zealand Pharma A/S | Acylated glucagon analogues |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| CN105829339B (zh) | 2013-11-06 | 2021-03-12 | 西兰制药公司 | 胰高血糖素-glp-1-gip三重激动剂化合物 |
| AU2014345569B2 (en) | 2013-11-06 | 2020-08-13 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
| US10435474B2 (en) | 2013-12-24 | 2019-10-08 | Ossianix, Inc. | Baff selective binding compounds and related methods |
| KR102500408B1 (ko) | 2014-01-27 | 2023-02-16 | 몰레큘러 템플레이츠, 인코퍼레이션. | 포유류에 적용하기 위한 탈면역된 시가 독소 a 서브유닛 작동체 폴리펩티드 |
| PL3604333T3 (pl) | 2014-03-11 | 2021-11-08 | Molecular Templates, Inc. | Białka zawierające regiony efektorowe podjednostki a toksyny shiga proksymalnie do końca aminowego oraz celujące w komórki regiony wiążące typu immunoglobuliny zdolne do swoistego wiązania cd38 |
| US20170002046A1 (en) | 2014-03-11 | 2017-01-05 | Molecular Templates, Inc. | Proteins comprising binding regions, shiga toxin a subunit effector regions, and carboxy-terminal, endoplasmic reticulum localization signal motifs |
| CN113831416A (zh) | 2014-06-11 | 2021-12-24 | 分子模板公司 | 耐受蛋白酶切割的志贺毒素a亚基效应子多肽和包含其的细胞靶向分子 |
| WO2015200883A2 (en) | 2014-06-26 | 2015-12-30 | Ossianix, Inc. | Semi-synthetic nurse shark vnar libraries for making and using selective binding compounds |
| EP3212218B1 (en) | 2014-10-29 | 2021-06-30 | Zealand Pharma A/S | Gip agonist compounds and methods |
| WO2016077840A2 (en) | 2014-11-14 | 2016-05-19 | Ossianix, Inc. | TfR SELECTIVE BINDING COMPOUNDS AND RELATED METHODS |
| ES2856457T3 (es) | 2015-02-05 | 2021-09-27 | Molecular Templates Inc | Moléculas de unión a CD20 multivalentes que comprenden regiones efectoras de una subunidad de toxina shiga y composiciones enriquecidas de estas |
| JP6769984B2 (ja) | 2015-03-18 | 2020-10-14 | ジーランド ファーマ アクティーゼルスカブ | アミリン類似体 |
| GB201506380D0 (en) | 2015-04-15 | 2015-05-27 | Serodus Asa | Materials and methods for treatment of pulmonary hypertension |
| CA2980978A1 (en) | 2015-04-16 | 2016-10-20 | Zealand Pharma A/S | Acylated glucagon analogue |
| CN107849096B (zh) | 2015-05-30 | 2022-05-24 | 分子模板公司 | 去免疫化的志贺毒素a亚基支架和包含它们的细胞靶向分子 |
| AU2016297920A1 (en) | 2015-07-26 | 2018-01-18 | Molecular Templates, Inc. | Cell-targeting molecules comprising shiga toxin A subunit effectors and CD8+ T-cell epitopes |
| CN108290923A (zh) | 2015-09-17 | 2018-07-17 | 麻省理工学院 | 用于固相肽合成的方法和系统 |
| US11097010B2 (en) | 2016-08-06 | 2021-08-24 | Ossianix, Inc. | In vivo methods for selecting peptides that cross the blood brain barrier, related compositions and methods of use |
| US10071140B2 (en) | 2016-09-09 | 2018-09-11 | Zealand Pharma A/S | Amylin analogues |
| WO2018103868A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| BR112019011859A2 (pt) | 2016-12-09 | 2019-10-29 | Zealand Pharma As | agonista duplo de glp-1/glp-2, composição, método para aumentar massa intestinal, método de profilaxia ou tratamento de má-absorção intestinal e uso de um agonista duplo |
| WO2018104559A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Glp-1/glp-2 dual agonists |
| WO2018104558A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| RU2753193C2 (ru) | 2016-12-09 | 2021-08-12 | Зилэнд Фарма А/С | Ацилированные двойные агонисты glp-1/glp-2 |
| MX2019008840A (es) | 2017-01-25 | 2019-09-09 | Molecular Templates Inc | Moleculas con direccion hacia las celulas que comprenden efectores de la sub-unidad a de la toxina shiga desinmunizados y epitopos de las celulas t cd8+. |
| ES2894629T3 (es) | 2017-06-16 | 2022-02-15 | Zealand Pharma As | Pautas posológicas para la administración de análogos del péptido 2 similar al glucagón (GLP-2) |
| CA3080351A1 (en) | 2017-11-02 | 2019-05-09 | Ossianix, Inc. | Improved tfr-selective binding peptides capable of crossing the blood brain barrier |
| JP7690287B2 (ja) | 2018-02-27 | 2025-06-10 | セトペー エスペーベー ３ コマンディト セルスカブ | コンプスタチン類似体及びその医療用途 |
| AU2019257343A1 (en) | 2018-04-17 | 2020-09-10 | Molecular Templates, Inc. | HER2-targeting molecules comprising de-immunized, Shiga toxin A Subunit scaffolds |
| US12258414B2 (en) | 2018-06-22 | 2025-03-25 | Ossianix, Inc. | Anti-CD98hc VNARs for crossing the blood brain barrier and type IV VNAR libraries |
| CA3100035A1 (en) | 2018-08-27 | 2020-03-05 | Regeneron Pharmaceuticals, Inc. | Use of raman spectroscopy in downstream purification |
| US12351642B2 (en) | 2018-09-14 | 2025-07-08 | Ossianix, Inc. | TFR-specific binding moieties and transcytosis method to select VNARs that cross cellular barriers |
| WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
| EP3914358A1 (en) | 2019-01-23 | 2021-12-01 | Millennium Pharmaceuticals, Inc. | Anti-cd38 antibodies |
| CA3127660A1 (en) | 2019-01-23 | 2020-07-30 | Millennium Pharmaceuticals, Inc. | Cd38-binding proteins comprising de-immunized shiga toxin a subunit effectors |
| EP3982920A1 (en) | 2019-06-14 | 2022-04-20 | Zealand Pharma A/S | Pharmaceutical parenteral composition of dual glp1/2 agonist |
| CN114630836A (zh) | 2019-08-27 | 2022-06-14 | 西兰制药第三特殊目的公司 | 补体抑制素类似物及其医学用途 |
| US11918649B2 (en) | 2019-09-18 | 2024-03-05 | Molecular Templates, Inc. | PD-L1-binding molecules comprising Shiga toxin a subunit scaffolds |
| TW202116350A (zh) | 2019-09-20 | 2021-05-01 | 丹麥商西蘭製藥公司 | Kv1.3阻斷劑 |
| US20210155671A1 (en) | 2019-11-24 | 2021-05-27 | Molecular Templates, Inc. | Uses of cd20-binding molecules and additional therapeutic agents |
| US20230129788A1 (en) | 2020-03-30 | 2023-04-27 | Zealand Pharma A/S | Glp-1/glp-2 dual agonists |
| US20230110689A1 (en) | 2020-03-30 | 2023-04-13 | Zealand Pharma A/S | Agonist combination |
| CN116209671A (zh) | 2020-07-16 | 2023-06-02 | 西兰制药第三特殊目的公司 | 补体因子c3的抑制剂及其医学用途 |
| WO2022103769A1 (en) | 2020-11-11 | 2022-05-19 | Ossianix, Inc. | High affinity human and monkey specific tfr-1 vnars |
| TW202241491A (zh) | 2020-12-16 | 2022-11-01 | 丹麥商西蘭製藥公司 | Ｇｌｐ－１／ｇｌｐ－２雙重促效劑之醫藥組合物 |
| WO2022129311A1 (en) | 2020-12-16 | 2022-06-23 | Zealand Pharma A/S | Pharmaceutical composition of glp-1/glp-2 dual agonists |
| US20240299552A1 (en) | 2020-12-16 | 2024-09-12 | Zealand Pharma A/S | Pharmaceutical Composition of GLP-1/GLP-2 Dual Agonists |
| US20240316155A1 (en) | 2021-02-18 | 2024-09-26 | Zealand Pharma A/S | Composition for treating short bowel syndrome |
| WO2022197945A1 (en) | 2021-03-17 | 2022-09-22 | Molecular Templates, Inc. | Pd-l1 binding proteins comprising shiga toxin a subunit scaffolds and cd8+ t cell antigens |
| AU2022245193A1 (en) | 2021-03-23 | 2023-09-07 | Zealand Pharma A/S | Kv1.3 blockers |
| WO2022260877A1 (en) | 2021-06-07 | 2022-12-15 | Ossianix, Inc. | Shark vnars for treating covid-19 |
| US20240279298A1 (en) | 2021-06-18 | 2024-08-22 | Beijing Tuo Jie Biopharmaceutical Co. Ltd. | Glucagon analog and medical use thereof |
| US20250122298A1 (en) | 2021-08-17 | 2025-04-17 | Ossianix, Inc. | Deimmunized vnar domains and scaffolds |
| JP2024533153A (ja) | 2021-09-03 | 2024-09-12 | ジーランド ファーマ エー／エス | 投薬レジーム |
| EP4440592A1 (en) | 2021-12-01 | 2024-10-09 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2024068848A1 (en) | 2022-09-28 | 2024-04-04 | Zealand Pharma A/S | Methods for treating obesity |
| EP4604984A1 (en) | 2022-10-18 | 2025-08-27 | Zealand Pharma A/S | Inhibitors |
| WO2024168411A1 (pt) * | 2023-02-15 | 2024-08-22 | Proteimax Bio Technology Israel Ltd | Aditivo de alimento e/ou suplemento alimentar, processo de obtenção, formulação de alimento funcional e/ou suplemento alimentar, uso |
| EP4471048A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| EP4471049A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2025056677A1 (en) | 2023-09-15 | 2025-03-20 | Zealand Pharma A/S | Dasiglucagon for use in the treatment of congenital hyperinsulinism |
| WO2025120002A1 (en) | 2023-12-04 | 2025-06-12 | Zealand Pharma A/S | Petrelintide for reducing weight whilst preserving lean mass |
| TW202530247A (zh) | 2023-12-04 | 2025-08-01 | 丹麥商西蘭製藥公司 | 方法 |
| WO2025248124A1 (en) | 2024-05-31 | 2025-12-04 | Zealand Pharma A/S | Dapiglutide for use in treating a sub-group of subjects |
| WO2025259861A2 (en) | 2024-06-12 | 2025-12-18 | Invaio Sciences, Inc. | Antimicrobial peptides against citrus greening |
| WO2025259842A2 (en) | 2024-06-12 | 2025-12-18 | Invaio Sciences, Inc. | Novel alpha-factor based peptides with antifungal activity |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5116666A (enExample) * | 1974-07-30 | 1976-02-10 | Shionogi Seiyaku Kk | |
| US5021550A (en) * | 1986-10-07 | 1991-06-04 | Thomas Jefferson University | Method for preventing deletion sequences in solid phase synthesis |
| JP2807287B2 (ja) * | 1989-10-13 | 1998-10-08 | 株式会社医学生物学研究所 | ペプチドおよびその用途 |
| EP0719334A1 (en) * | 1993-09-14 | 1996-07-03 | Genentech, Inc. | Pharmaceutical compositions containing ecotin and homologs thereof |
| US7176282B1 (en) * | 1996-09-09 | 2007-02-13 | Zealand Pharma A/S | Solid-phase peptide synthesis and agent for use in such synthesis |
| IL138214A0 (en) * | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
-
1997
- 1997-09-09 IL IL12882997A patent/IL128829A/xx not_active IP Right Cessation
- 1997-09-09 DK DK97939974T patent/DK0929567T3/da active
- 1997-09-09 EP EP97939974A patent/EP0929567B1/en not_active Expired - Lifetime
- 1997-09-09 DE DE69732640T patent/DE69732640T2/de not_active Expired - Lifetime
- 1997-09-09 PT PT97939974T patent/PT929567E/pt unknown
- 1997-09-09 AT AT97939974T patent/ATE290014T1/de active
- 1997-09-09 JP JP51316698A patent/JP4405594B2/ja not_active Expired - Fee Related
- 1997-09-09 CA CA002265900A patent/CA2265900C/en not_active Expired - Lifetime
- 1997-09-09 HU HU0102900A patent/HU230354B1/hu not_active IP Right Cessation
- 1997-09-09 CZ CZ1999803A patent/CZ295838B6/cs not_active IP Right Cessation
- 1997-09-09 ES ES97939974T patent/ES2239364T3/es not_active Expired - Lifetime
- 1997-09-09 AU AU41993/97A patent/AU723268B2/en not_active Ceased
- 1997-09-09 WO PCT/DK1997/000375 patent/WO1998011125A1/en not_active Ceased
-
2006
- 2006-06-19 US US11/455,388 patent/US7348404B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0929567A1 (en) | 1999-07-21 |
| CA2265900A1 (en) | 1998-03-19 |
| HU230354B1 (hu) | 2016-02-29 |
| IL128829A (en) | 2005-08-31 |
| CZ295838B6 (cs) | 2005-11-16 |
| HUP0102900A3 (en) | 2002-02-28 |
| CZ80399A3 (cs) | 1999-08-11 |
| ES2239364T3 (es) | 2005-09-16 |
| JP4405594B2 (ja) | 2010-01-27 |
| WO1998011125A1 (en) | 1998-03-19 |
| JP2001500134A (ja) | 2001-01-09 |
| AU723268B2 (en) | 2000-08-24 |
| US20070004905A1 (en) | 2007-01-04 |
| DK0929567T3 (da) | 2005-06-27 |
| US7348404B2 (en) | 2008-03-25 |
| HUP0102900A2 (hu) | 2002-01-28 |
| PT929567E (pt) | 2005-07-29 |
| CA2265900C (en) | 2007-07-31 |
| AU4199397A (en) | 1998-04-02 |
| IL128829A0 (en) | 2000-01-31 |
| DE69732640D1 (de) | 2005-04-07 |
| EP0929567B1 (en) | 2005-03-02 |
| ATE290014T1 (de) | 2005-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69732640T2 (de) | Festphasen-peptidsynthese | |
| EP0285562B1 (de) | Kunstharz | |
| DE68926178T2 (de) | Festphase-Verfahren zur Gewinnung von Thymosin-alpha-1 | |
| DE3788910T2 (de) | Methode für die Synthese eines Peptides, das eine nicht peptidartige Bindung enthält. | |
| DE69222091T2 (de) | Peptid-Synthese an fester Phase | |
| DE602004001727T2 (de) | Verfahren zur herstellung cyclischer peptide | |
| CN107056927B (zh) | 一种利拉鲁肽的制备方法 | |
| DE69926061T2 (de) | Verfahren und zusammensetzungen zur peptidsynthese (t-20) | |
| EP4436991A1 (en) | Process for the preparation of tirzepatide or pharmaceutically acceptable salt thereof | |
| DE3782010T2 (de) | Vom calcitonin-gen abgeleitete peptidderivate. | |
| DE3688632T2 (de) | Verfahren zur Herstellung von Peptiden in fester Phase. | |
| EP1179537B1 (en) | Solid phase peptide synthesis method | |
| DE69219672T2 (de) | Peptid-Synthese an fester Phase | |
| EP0292729B1 (de) | Neue Festphasen-Peptidsynthesemethoden | |
| DE60226324T2 (de) | Glykopeptide, deren herstellung und verwendung in der diagnose oder behandlung von multipler sklerose | |
| CN111018962A (zh) | 一种基于固相逐步法的制备替度鲁肽的方法 | |
| US7176282B1 (en) | Solid-phase peptide synthesis and agent for use in such synthesis | |
| EP0051205B1 (de) | Neues Tridekapeptid, Verfahren zu seiner Herstellung und Verwendung | |
| JP2563284B2 (ja) | 過塩素酸塩使用によるペプチドの製造方法 | |
| EP0295540B1 (de) | Allylische Seitenketten enthaltendes Festphasensystem, Verfahren zu seiner Herstellung und seine Verwendung in Festphasenreaktionen | |
| US20230406900A1 (en) | Process for preparing glucagon-like peptide-1 | |
| KR20230167199A (ko) | 펩타이드 정제방법 및 그를 이용하여 정제된 펩타이드 | |
| DE68912090T2 (de) | Calcitonin-Derivate und deren Salze. | |
| DE3931731C2 (de) | Verfahren zur Festphasenpeptidsynthese | |
| Cavallaro et al. | Solid‐phase synthesis of a dendritic peptide related to a retinoblastoma protein fragment utilizing a combined boc‐and fmoc‐chemistry approach |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |