NZ507083A - Methods and compositions for peptide synthesis, in particular T-20 (DP-178) and T-20-like peptides - Google Patents
Methods and compositions for peptide synthesis, in particular T-20 (DP-178) and T-20-like peptidesInfo
- Publication number
- NZ507083A NZ507083A NZ507083A NZ50708399A NZ507083A NZ 507083 A NZ507083 A NZ 507083A NZ 507083 A NZ507083 A NZ 507083A NZ 50708399 A NZ50708399 A NZ 50708399A NZ 507083 A NZ507083 A NZ 507083A
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- formula
- peptide
- fmoc
- protected peptide
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 286
- 238000000034 method Methods 0.000 title claims abstract description 172
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 title claims abstract description 160
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 68
- 238000010647 peptide synthesis reaction Methods 0.000 title description 10
- 239000000203 mixture Substances 0.000 title description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 80
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 79
- 108010033276 Peptide Fragments Proteins 0.000 claims abstract description 45
- 102000007079 Peptide Fragments Human genes 0.000 claims abstract description 45
- 235000011468 Albizia julibrissin Nutrition 0.000 claims description 110
- 241001070944 Mimosa Species 0.000 claims description 110
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 230000004048 modification Effects 0.000 claims description 13
- 238000012986 modification Methods 0.000 claims description 13
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 4
- CSHFHJNMIMPJST-HOTGVXAUSA-N methyl (2s)-2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoate Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)OC)CC1=CC=CC=C1 CSHFHJNMIMPJST-HOTGVXAUSA-N 0.000 claims 1
- 239000012634 fragment Substances 0.000 abstract description 163
- 239000000543 intermediate Substances 0.000 abstract description 47
- 239000007790 solid phase Substances 0.000 abstract description 25
- 239000007791 liquid phase Substances 0.000 abstract description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 485
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 252
- 229920005989 resin Polymers 0.000 description 222
- 239000011347 resin Substances 0.000 description 222
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 176
- 239000000243 solution Substances 0.000 description 156
- 239000007787 solid Substances 0.000 description 151
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 147
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 114
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 101
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 96
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 95
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 82
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- 150000001413 amino acids Chemical group 0.000 description 72
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
- 229940024606 amino acid Drugs 0.000 description 67
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 61
- 238000005859 coupling reaction Methods 0.000 description 61
- 238000004128 high performance liquid chromatography Methods 0.000 description 61
- 235000001014 amino acid Nutrition 0.000 description 59
- 238000003828 vacuum filtration Methods 0.000 description 57
- 238000011068 loading method Methods 0.000 description 53
- 239000000047 product Substances 0.000 description 51
- 230000014759 maintenance of location Effects 0.000 description 48
- 238000002360 preparation method Methods 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
- 238000010168 coupling process Methods 0.000 description 47
- 239000000463 material Substances 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000003756 stirring Methods 0.000 description 45
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 44
- 230000008878 coupling Effects 0.000 description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
- 229910052757 nitrogen Inorganic materials 0.000 description 41
- 238000012360 testing method Methods 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 239000012071 phase Substances 0.000 description 37
- 235000019441 ethanol Nutrition 0.000 description 36
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 33
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 30
- 239000002002 slurry Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- 238000003776 cleavage reaction Methods 0.000 description 28
- 230000007017 scission Effects 0.000 description 28
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
- 238000012369 In process control Methods 0.000 description 27
- 238000010965 in-process control Methods 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- ZYASLTYCYTYKFC-UHFFFAOYSA-N 9-methylidenefluorene Chemical compound C1=CC=C2C(=C)C3=CC=CC=C3C2=C1 ZYASLTYCYTYKFC-UHFFFAOYSA-N 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
- 238000013459 approach Methods 0.000 description 21
- 238000001514 detection method Methods 0.000 description 21
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 19
- 238000010511 deprotection reaction Methods 0.000 description 18
- 238000001035 drying Methods 0.000 description 18
- -1 or alternatively Chemical compound 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- ADOHASQZJSJZBT-SANMLTNESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C12=CC=CC=C2N(C(=O)OC(C)(C)C)C=C1C[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ADOHASQZJSJZBT-SANMLTNESA-N 0.000 description 16
- 239000012298 atmosphere Substances 0.000 description 16
- 125000006239 protecting group Chemical group 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000523 sample Substances 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 238000001556 precipitation Methods 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- 238000001665 trituration Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000004821 distillation Methods 0.000 description 12
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
- 239000012535 impurity Substances 0.000 description 12
- PGTKVMVZBBZCKQ-UHFFFAOYSA-N Fulvene Chemical compound C=C1C=CC=C1 PGTKVMVZBBZCKQ-UHFFFAOYSA-N 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 238000010532 solid phase synthesis reaction Methods 0.000 description 11
- 230000004584 weight gain Effects 0.000 description 11
- 235000019786 weight gain Nutrition 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000006227 byproduct Substances 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- 238000010268 HPLC based assay Methods 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 239000011630 iodine Substances 0.000 description 9
- 238000010926 purge Methods 0.000 description 9
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 238000006114 decarboxylation reaction Methods 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 229960004592 isopropanol Drugs 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 230000008961 swelling Effects 0.000 description 8
- 238000013019 agitation Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical compound NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 230000006340 racemization Effects 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- MGHMWKZOLAAOTD-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(1h-indol-3-yl)propanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC(C(=O)O)CC1=CNC2=CC=CC=C12 MGHMWKZOLAAOTD-UHFFFAOYSA-N 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 5
- 229910004373 HOAc Inorganic materials 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000005587 bubbling Effects 0.000 description 5
- DAKIDYQCFJQMDF-UHFFFAOYSA-N dichloromethane;pyridine Chemical compound ClCCl.C1=CC=NC=C1 DAKIDYQCFJQMDF-UHFFFAOYSA-N 0.000 description 5
- MBCZNRXYDIFUJF-UHFFFAOYSA-N fulvene;piperidine Chemical compound C=C1C=CC=C1.C1CCNCC1 MBCZNRXYDIFUJF-UHFFFAOYSA-N 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- SWZCTMTWRHEBIN-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C1=CC=C(O)C=C1 SWZCTMTWRHEBIN-QFIPXVFZSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- MJZMSEWWBGCBFM-UHFFFAOYSA-N 2-(2-acetamidopropanoylamino)propanoic acid Chemical compound OC(=O)C(C)NC(=O)C(C)NC(C)=O MJZMSEWWBGCBFM-UHFFFAOYSA-N 0.000 description 4
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000001143 conditioned effect Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
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-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/045,920 US6281331B1 (en) | 1998-03-23 | 1998-03-23 | Methods and compositions for peptide synthesis |
| US09/071,877 US6015881A (en) | 1998-03-23 | 1998-05-01 | Methods and compositions for peptide synthesis |
| PCT/US1999/006230 WO1999048513A1 (en) | 1998-03-23 | 1999-03-22 | Methods and compositions for peptide synthesis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ507083A true NZ507083A (en) | 2003-10-31 |
Family
ID=26723345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ507083A NZ507083A (en) | 1998-03-23 | 1999-03-22 | Methods and compositions for peptide synthesis, in particular T-20 (DP-178) and T-20-like peptides |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1071442B9 (https=) |
| JP (1) | JP4602547B2 (https=) |
| CN (1) | CN100383158C (https=) |
| AT (1) | ATE299029T1 (https=) |
| AU (1) | AU751358B2 (https=) |
| BR (1) | BR9909018A (https=) |
| CA (1) | CA2324348C (https=) |
| DE (1) | DE69926061T2 (https=) |
| DK (1) | DK1071442T3 (https=) |
| ES (1) | ES2245505T3 (https=) |
| NZ (1) | NZ507083A (https=) |
| TW (1) | TWI233931B (https=) |
| WO (1) | WO1999048513A1 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6281331B1 (en) * | 1998-03-23 | 2001-08-28 | Trimeris, Inc. | Methods and compositions for peptide synthesis |
| US6469136B1 (en) * | 1999-07-07 | 2002-10-22 | Trimeris, Inc. | Methods and composition for peptide synthesis |
| AU2002314111A1 (en) | 2001-06-15 | 2003-01-02 | F. Hoffmann-La Roche Ag | Method for the recombinant production of peptidic antiviral fusion inhibitors, and acetylation of gb41 fragments |
| HRP20050024A2 (en) * | 2002-07-24 | 2006-02-28 | F. Hoffmann - La Roche Ag | Pegylated t20 polypeptide |
| ES2295961T3 (es) | 2003-12-31 | 2008-04-16 | F. Hoffmann-La Roche Ag | Proceso para la sintesis peptidica utilizacndo una cantidad reducida de agente de desproteccion. |
| EP1701976A2 (en) * | 2003-12-31 | 2006-09-20 | F.Hoffmann-La Roche Ag | Peptide synthesis and deprotection with co-solvent |
| ATE410437T1 (de) | 2003-12-31 | 2008-10-15 | Hoffmann La Roche | Verfahren und systeme zur rückgewinnung von peptiden |
| JP4886702B2 (ja) * | 2004-12-30 | 2012-02-29 | エフ．ホフマン−ラ ロシュ アーゲー | ペプチド中間体断片を使用するペプチドｔ−２０の合成 |
| US8022181B2 (en) | 2006-05-03 | 2011-09-20 | Mallinckrodt Llc | Composition and method for the release of protected peptides from a resin |
| EP2181983A4 (en) * | 2007-07-25 | 2013-01-02 | Ajinomoto Kk | METHOD FOR THE SELECTIVE REMOVAL OF A DIBENZOFULVENE DERIVATIVE |
| JP5473925B2 (ja) * | 2007-10-27 | 2014-04-16 | コーデン ファーマ コロラド インコーポレイテッド | 固相および溶液相の組み合わせ技法を使用するインスリン分泌性ペプチドの合成 |
| BRPI0820765A2 (pt) * | 2007-12-11 | 2015-06-16 | Hoffmann La Roche | Métodos para a produção de um peptídeo insulinotrópico e peptídeos |
| JP5445456B2 (ja) | 2008-08-06 | 2014-03-19 | 味の素株式会社 | ジベンゾフルベンの除去方法 |
| US20110288235A1 (en) * | 2008-09-03 | 2011-11-24 | Scinopharm Taiwan Ltd. | Process for the Preparation of Pramlintide |
| WO2010028131A1 (en) * | 2008-09-03 | 2010-03-11 | Scinopharm Taiwan Ltd. | Process for the preparation of pramlintide |
| WO2011095989A2 (en) * | 2010-02-04 | 2011-08-11 | Matrix Laboratories Ltd | An improved process for the preparation of enfuvirtide |
| PL219569B1 (pl) * | 2010-02-19 | 2015-05-29 | Peptaderm Spółka Z Ograniczoną Odpowiedzialnością | Cykliczne tetrapeptydy i ich zastosowanie |
| CN103374054B (zh) * | 2012-04-28 | 2014-12-24 | 上海第一生化药业有限公司 | 一步法固相合成多肽的方法 |
| GB201315335D0 (en) | 2013-08-29 | 2013-10-09 | Of Singapore | Amino diacids containing peptide modifiers |
| IL295109A (en) * | 2020-02-05 | 2022-09-01 | Lilly Co Eli | Resin miners in a serial peptide synthesizer |
| CN114315957B (zh) * | 2021-12-30 | 2023-07-07 | 深圳瑞德林生物技术有限公司 | 一种多肽的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0269712A4 (en) * | 1986-06-12 | 1990-06-26 | Biogen Nv | PEPTIDES INVOLVED IN THE PATHOGENESIS OF A HIV TYPE INFECTION. |
| US4787222A (en) * | 1986-11-24 | 1988-11-29 | Novatek Medical Inc. | Combination lock for blood identification system |
| US5444044A (en) * | 1992-03-26 | 1995-08-22 | New York Blood Center | Synthetic polypeptides as inhibitors of HIV-1 |
| US5464933A (en) * | 1993-06-07 | 1995-11-07 | Duke University | Synthetic peptide inhibitors of HIV transmission |
| EP0708659A4 (en) * | 1993-06-07 | 2000-08-23 | Genentech Inc | HIV ENVELOPE POLYPEPTIDES |
| US6479055B1 (en) * | 1993-06-07 | 2002-11-12 | Trimeris, Inc. | Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission |
| DE69426725T2 (de) * | 1993-09-11 | 2001-09-06 | Polimun Scientific Immunbiologische Forschungsgesellschaft Mbh, Wien | Peptide, die neutralisierende antikörper gegen genetisch divergierende hiv-1 stämme, induzieren |
| AU722895B2 (en) * | 1996-02-09 | 2000-08-10 | F. Hoffmann-La Roche Ag | Synthesis of VIP analog |
-
1999
- 1999-03-22 CA CA002324348A patent/CA2324348C/en not_active Expired - Lifetime
- 1999-03-22 AT AT99912802T patent/ATE299029T1/de active
- 1999-03-22 CN CNB998064319A patent/CN100383158C/zh not_active Expired - Fee Related
- 1999-03-22 DE DE69926061T patent/DE69926061T2/de not_active Expired - Lifetime
- 1999-03-22 NZ NZ507083A patent/NZ507083A/en not_active IP Right Cessation
- 1999-03-22 EP EP99912802A patent/EP1071442B9/en not_active Expired - Lifetime
- 1999-03-22 JP JP2000537561A patent/JP4602547B2/ja not_active Expired - Fee Related
- 1999-03-22 WO PCT/US1999/006230 patent/WO1999048513A1/en not_active Ceased
- 1999-03-22 BR BR9909018-0A patent/BR9909018A/pt not_active IP Right Cessation
- 1999-03-22 AU AU31097/99A patent/AU751358B2/en not_active Expired
- 1999-03-22 DK DK99912802T patent/DK1071442T3/da active
- 1999-03-22 ES ES99912802T patent/ES2245505T3/es not_active Expired - Lifetime
- 1999-03-23 TW TW088104562A patent/TWI233931B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1071442B1 (en) | 2005-07-06 |
| EP1071442A1 (en) | 2001-01-31 |
| CN100383158C (zh) | 2008-04-23 |
| ES2245505T3 (es) | 2006-01-01 |
| AU3109799A (en) | 1999-10-18 |
| TWI233931B (en) | 2005-06-11 |
| DE69926061T2 (de) | 2006-06-01 |
| JP4602547B2 (ja) | 2010-12-22 |
| CA2324348C (en) | 2006-03-14 |
| BR9909018A (pt) | 2001-10-16 |
| DE69926061D1 (de) | 2005-08-11 |
| ATE299029T1 (de) | 2005-07-15 |
| CN1303299A (zh) | 2001-07-11 |
| EP1071442B9 (en) | 2006-01-18 |
| DK1071442T3 (da) | 2005-10-24 |
| AU751358B2 (en) | 2002-08-15 |
| WO1999048513A1 (en) | 1999-09-30 |
| EP1071442A4 (en) | 2002-06-05 |
| CA2324348A1 (en) | 1999-09-30 |
| JP2002507576A (ja) | 2002-03-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RENW | Renewal (renewal fees accepted) | ||
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| EXPY | Patent expired |