IL182575A - On-resin peptide cyclization - Google Patents
On-resin peptide cyclizationInfo
- Publication number
- IL182575A IL182575A IL182575A IL18257507A IL182575A IL 182575 A IL182575 A IL 182575A IL 182575 A IL182575 A IL 182575A IL 18257507 A IL18257507 A IL 18257507A IL 182575 A IL182575 A IL 182575A
- Authority
- IL
- Israel
- Prior art keywords
- peptide
- cysteine
- amino acid
- resin
- solid phase
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 106
- 229920005989 resin Polymers 0.000 title claims description 72
- 239000011347 resin Substances 0.000 title claims description 72
- 238000007363 ring formation reaction Methods 0.000 title description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 239000007790 solid phase Substances 0.000 claims description 52
- -1 S-tert-butylsulphanyl group Chemical group 0.000 claims description 45
- 238000005859 coupling reaction Methods 0.000 claims description 39
- 238000010168 coupling process Methods 0.000 claims description 37
- 230000008878 coupling Effects 0.000 claims description 36
- 235000018417 cysteine Nutrition 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 23
- 239000003153 chemical reaction reagent Substances 0.000 claims description 22
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- 238000010511 deprotection reaction Methods 0.000 claims description 21
- 150000001408 amides Chemical class 0.000 claims description 13
- 235000001014 amino acid Nutrition 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 238000010647 peptide synthesis reaction Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 125000000539 amino acid group Chemical group 0.000 claims description 9
- 210000004899 c-terminal region Anatomy 0.000 claims description 8
- 150000002148 esters Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 150000007970 thio esters Chemical class 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 238000006664 bond formation reaction Methods 0.000 claims description 4
- 108010069514 Cyclic Peptides Proteins 0.000 claims description 3
- 102000001189 Cyclic Peptides Human genes 0.000 claims description 3
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 229940080818 propionamide Drugs 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 32
- 238000003776 cleavage reaction Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 230000007017 scission Effects 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 10
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 10
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
- 125000005647 linker group Chemical group 0.000 description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
- 125000005500 uronium group Chemical group 0.000 description 9
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical class C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000000654 additive Substances 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- VORIUEAZEKLUSJ-UHFFFAOYSA-M [(6-chlorobenzotriazol-1-yl)oxy-(dimethylamino)methylidene]-dimethylazanium;trifluoroborane;fluoride Chemical compound [F-].FB(F)F.C1=C(Cl)C=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 VORIUEAZEKLUSJ-UHFFFAOYSA-M 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- 238000010532 solid phase synthesis reaction Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000004007 reversed phase HPLC 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
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 5
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 4
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 238000004873 anchoring Methods 0.000 description 4
- 125000002228 disulfide group Chemical group 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 150000003003 phosphines Chemical group 0.000 description 4
- 150000004714 phosphonium salts Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- FNQIGYRDLYROLW-UHFFFAOYSA-N 1-hydroxy-2h-1,2,3-benzotriazine Chemical group C1=CC=C2N(O)NN=CC2=C1 FNQIGYRDLYROLW-UHFFFAOYSA-N 0.000 description 2
- HXOYWJCDYVODON-UHFFFAOYSA-N 4-[4-(hydroxymethyl)-3-methoxyphenoxy]butanoic acid Chemical compound COC1=CC(OCCCC(O)=O)=CC=C1CO HXOYWJCDYVODON-UHFFFAOYSA-N 0.000 description 2
- 108010056764 Eptifibatide Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
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- 239000006184 cosolvent Substances 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 description 2
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- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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- 125000001151 peptidyl group Chemical group 0.000 description 2
- 239000003880 polar aprotic solvent Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical group CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 description 2
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- 238000007086 side reaction Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
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- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 2
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- 150000003573 thiols Chemical group 0.000 description 2
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- YEDNBEGNKOANMB-REOHCLBHSA-N (2r)-2-amino-3-sulfanylpropanamide Chemical group SC[C@H](N)C(N)=O YEDNBEGNKOANMB-REOHCLBHSA-N 0.000 description 1
- VXGGBPQPMISJCA-STQMWFEESA-N (2s)-2-[[(2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 VXGGBPQPMISJCA-STQMWFEESA-N 0.000 description 1
- XSYUPRQVAHJETO-WPMUBMLPSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidaz Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 XSYUPRQVAHJETO-WPMUBMLPSA-N 0.000 description 1
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- 125000000134 2-(methylsulfanyl)ethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])[*] 0.000 description 1
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 229920000361 Poly(styrene)-block-poly(ethylene glycol) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 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
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000004697 chelate complex Chemical class 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- ORQXBVXKBGUSBA-UHFFFAOYSA-N cyclohexyl D-alanine Natural products OC(=O)C(N)CC1CCCCC1 ORQXBVXKBGUSBA-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- MDDRQVPVBIQMQV-UHFFFAOYSA-N ethyl chlorosulfanylformate Chemical compound CCOC(=O)SCl MDDRQVPVBIQMQV-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical group N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 230000006919 peptide aggregation Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001225 polyester resin Polymers 0.000 description 1
- 239000004645 polyester resin Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical group CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- UYUUAUOYLFIRJG-UHFFFAOYSA-N tris(4-methoxyphenyl)phosphane Chemical compound C1=CC(OC)=CC=C1P(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 UYUUAUOYLFIRJG-UHFFFAOYSA-N 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 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
- C07K1/06—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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Polyamides (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04024813 | 2004-10-19 | ||
| EP05008979 | 2005-04-25 | ||
| PCT/EP2005/011182 WO2006045483A2 (en) | 2004-10-19 | 2005-10-18 | On-resin peptide cyclization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL182575A0 IL182575A0 (en) | 2007-07-24 |
| IL182575A true IL182575A (en) | 2012-07-31 |
Family
ID=36096370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL182575A IL182575A (en) | 2004-10-19 | 2007-04-16 | On-resin peptide cyclization |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7994280B2 (enExample) |
| EP (1) | EP1805203B1 (enExample) |
| JP (1) | JP4927746B2 (enExample) |
| KR (2) | KR101222774B1 (enExample) |
| CN (1) | CN101111510B (enExample) |
| AT (1) | ATE455123T1 (enExample) |
| AU (1) | AU2005298991B2 (enExample) |
| BR (1) | BRPI0516929A (enExample) |
| CA (1) | CA2588098A1 (enExample) |
| DE (1) | DE602005018952D1 (enExample) |
| DK (1) | DK1805203T3 (enExample) |
| ES (1) | ES2339791T3 (enExample) |
| IL (1) | IL182575A (enExample) |
| PT (1) | PT1805203E (enExample) |
| TW (1) | TW200628487A (enExample) |
| WO (1) | WO2006045483A2 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101538316B (zh) * | 2009-01-13 | 2012-09-05 | 深圳翰宇药业股份有限公司 | 一种固相法制备Eptifibatide的方法 |
| WO2013112548A1 (en) * | 2012-01-23 | 2013-08-01 | University Of South Florida | Gamma-aapeptides with potent and broad-spectrum antimicrobial activity |
| CN108218964A (zh) * | 2018-01-30 | 2018-06-29 | 江南大学 | 一种固相载体上酶法合成环肽方法 |
| WO2024234959A1 (en) * | 2023-05-18 | 2024-11-21 | Versitech Limited | Late-stage peptide cyclization to form disulfide mimetics |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4606856A (en) * | 1985-03-18 | 1986-08-19 | Seyler Jay K | [Des-1-amino, 8-glycine]calcitonin |
| US5770687A (en) * | 1995-06-07 | 1998-06-23 | Peptor Limited | Comformationally constrained backbone cyclized somatostatin analogs |
| WO2003093302A2 (en) * | 2002-05-03 | 2003-11-13 | Avecia Limited | Process for the synthesis of peptides amides by side-chain attachement to a solid phase |
| CN1222537C (zh) * | 2002-11-14 | 2005-10-12 | 吉尔生化（上海）有限公司 | 一种制备依非巴特的工艺 |
| WO2004092202A1 (en) | 2003-04-07 | 2004-10-28 | Novetide, Ltd. | Process for production of cyclic peptides |
| EP1756141B1 (en) | 2004-06-14 | 2009-12-09 | USV Ltd. | Process for the preparation of peptides |
| CN100500805C (zh) * | 2006-11-07 | 2009-06-17 | 武汉钢铁集团鄂城钢铁有限责任公司 | 除尘焦粉回配煤炼焦方法及其工艺 |
-
2005
- 2005-10-18 BR BRPI0516929-1A patent/BRPI0516929A/pt not_active IP Right Cessation
- 2005-10-18 KR KR1020077010506A patent/KR101222774B1/ko not_active Expired - Fee Related
- 2005-10-18 PT PT05796237T patent/PT1805203E/pt unknown
- 2005-10-18 CN CN2005800435892A patent/CN101111510B/zh not_active Expired - Fee Related
- 2005-10-18 ES ES05796237T patent/ES2339791T3/es not_active Expired - Lifetime
- 2005-10-18 US US11/665,537 patent/US7994280B2/en not_active Expired - Fee Related
- 2005-10-18 AT AT05796237T patent/ATE455123T1/de not_active IP Right Cessation
- 2005-10-18 AU AU2005298991A patent/AU2005298991B2/en not_active Ceased
- 2005-10-18 DE DE602005018952T patent/DE602005018952D1/de not_active Expired - Lifetime
- 2005-10-18 EP EP05796237A patent/EP1805203B1/en not_active Expired - Lifetime
- 2005-10-18 JP JP2007537183A patent/JP4927746B2/ja not_active Expired - Fee Related
- 2005-10-18 CA CA002588098A patent/CA2588098A1/en not_active Abandoned
- 2005-10-18 TW TW094136279A patent/TW200628487A/zh unknown
- 2005-10-18 KR KR1020127016164A patent/KR101276463B1/ko not_active Expired - Fee Related
- 2005-10-18 WO PCT/EP2005/011182 patent/WO2006045483A2/en not_active Ceased
- 2005-10-18 DK DK05796237.5T patent/DK1805203T3/da active
-
2007
- 2007-04-16 IL IL182575A patent/IL182575A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006045483A3 (en) | 2006-07-13 |
| DK1805203T3 (da) | 2010-05-17 |
| IL182575A0 (en) | 2007-07-24 |
| KR20070084099A (ko) | 2007-08-24 |
| WO2006045483A2 (en) | 2006-05-04 |
| AU2005298991B2 (en) | 2011-03-03 |
| PT1805203E (pt) | 2010-04-19 |
| JP4927746B2 (ja) | 2012-05-09 |
| BRPI0516929A (pt) | 2008-09-23 |
| TW200628487A (en) | 2006-08-16 |
| US20080200647A1 (en) | 2008-08-21 |
| US7994280B2 (en) | 2011-08-09 |
| AU2005298991A1 (en) | 2006-05-04 |
| KR101222774B1 (ko) | 2013-01-15 |
| EP1805203A2 (en) | 2007-07-11 |
| ATE455123T1 (de) | 2010-01-15 |
| CN101111510A (zh) | 2008-01-23 |
| CA2588098A1 (en) | 2006-05-04 |
| KR101276463B1 (ko) | 2013-06-19 |
| DE602005018952D1 (de) | 2010-03-04 |
| KR20120088855A (ko) | 2012-08-08 |
| JP2008517016A (ja) | 2008-05-22 |
| ES2339791T3 (es) | 2010-05-25 |
| EP1805203B1 (en) | 2010-01-13 |
| CN101111510B (zh) | 2011-09-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed |