JPS59159828A - 反応性重合体の製造法 - Google Patents
反応性重合体の製造法Info
- Publication number
- JPS59159828A JPS59159828A JP3295683A JP3295683A JPS59159828A JP S59159828 A JPS59159828 A JP S59159828A JP 3295683 A JP3295683 A JP 3295683A JP 3295683 A JP3295683 A JP 3295683A JP S59159828 A JPS59159828 A JP S59159828A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- active
- represented
- polymer
- 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.)
- Granted
Links
- 229920013730 reactive polymer Polymers 0.000 title claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 24
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 46
- -1 2-pyridylthio Chemical group 0.000 claims abstract description 23
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 13
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 9
- 239000000470 constituent Substances 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims 1
- 229920000642 polymer Polymers 0.000 abstract description 38
- 239000000126 substance Substances 0.000 abstract description 29
- 231100000433 cytotoxic Toxicity 0.000 abstract description 18
- 230000001472 cytotoxic effect Effects 0.000 abstract description 18
- 239000002246 antineoplastic agent Substances 0.000 abstract description 11
- 238000009739 binding Methods 0.000 abstract description 9
- 239000003795 chemical substances by application Substances 0.000 abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 6
- 125000004434 sulfur atom Chemical group 0.000 abstract description 4
- 210000004881 tumor cell Anatomy 0.000 abstract description 4
- 150000001768 cations Chemical class 0.000 abstract description 2
- 230000003327 cancerostatic effect Effects 0.000 abstract 2
- 230000000118 anti-neoplastic effect Effects 0.000 abstract 1
- 229940034982 antineoplastic agent Drugs 0.000 abstract 1
- 125000000962 organic group Chemical group 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 46
- 239000000243 solution Substances 0.000 description 35
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 28
- 238000000034 method Methods 0.000 description 27
- 108060003951 Immunoglobulin Proteins 0.000 description 22
- 102000018358 immunoglobulin Human genes 0.000 description 22
- 229960002989 glutamic acid Drugs 0.000 description 20
- 229920002643 polyglutamic acid Polymers 0.000 description 18
- 229960003767 alanine Drugs 0.000 description 12
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 229920001577 copolymer Polymers 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000000502 dialysis Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical group CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 8
- 239000004220 glutamic acid Substances 0.000 description 8
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 8
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 7
- 150000001412 amines Chemical group 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- 125000002228 disulfide group Chemical group 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 229940041181 antineoplastic drug Drugs 0.000 description 6
- 235000013922 glutamic acid Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- 229920000298 Cellophane Polymers 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- XNCSCQSQSGDGES-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]propyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C(C)CN(CC(O)=O)CC(O)=O XNCSCQSQSGDGES-UHFFFAOYSA-N 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 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
- 150000001371 alpha-amino acids Chemical class 0.000 description 3
- 235000008206 alpha-amino acids Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- REYLLNRLWCBKCM-YFKPBYRVSA-N (2s)-2-acetamido-4-sulfanylbutanoic acid Chemical group CC(=O)N[C@H](C(O)=O)CCS REYLLNRLWCBKCM-YFKPBYRVSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BGGHCRNCRWQABU-JTQLQIEISA-N (2s)-2-amino-5-oxo-5-phenylmethoxypentanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)OCC1=CC=CC=C1 BGGHCRNCRWQABU-JTQLQIEISA-N 0.000 description 1
- TYFDKHAZLDQMNA-YUMQZZPRSA-N (2s)-4-[[(3s)-3-acetamido-3-carboxypropyl]disulfanyl]-2-aminobutanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)CCSSCC[C@H](N)C(O)=O TYFDKHAZLDQMNA-YUMQZZPRSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ZJGBFJBMTKEFNQ-UHFFFAOYSA-N 3-(2,5-dioxopyrrol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 ZJGBFJBMTKEFNQ-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- DJBRKGZFUXKLKO-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanoic acid Chemical compound OC(=O)CCSSC1=CC=CC=N1 DJBRKGZFUXKLKO-UHFFFAOYSA-N 0.000 description 1
- OROGUZVNAFJPHA-UHFFFAOYSA-N 3-hydroxy-2,4-dimethyl-2H-thiophen-5-one Chemical compound CC1SC(=O)C(C)=C1O OROGUZVNAFJPHA-UHFFFAOYSA-N 0.000 description 1
- UHBAPGWWRFVTFS-UHFFFAOYSA-N 4,4'-dipyridyl disulfide Chemical compound C=1C=NC=CC=1SSC1=CC=NC=C1 UHBAPGWWRFVTFS-UHFFFAOYSA-N 0.000 description 1
- LMJXSOYPAOSIPZ-UHFFFAOYSA-N 4-sulfanylbenzoic acid Chemical group OC(=O)C1=CC=C(S)C=C1 LMJXSOYPAOSIPZ-UHFFFAOYSA-N 0.000 description 1
- KIUMMUBSPKGMOY-UHFFFAOYSA-L 5-[(3-carboxylato-4-nitrophenyl)disulfanyl]-2-nitrobenzoate 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-L 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical group C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 241000690527 Mydosama terminus Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004414 alkyl thio group Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical group O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 108010052780 polyasparagine Proteins 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000003774 sulfhydryl reagent Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Polyamides (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3295683A JPS59159828A (ja) | 1983-03-02 | 1983-03-02 | 反応性重合体の製造法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3295683A JPS59159828A (ja) | 1983-03-02 | 1983-03-02 | 反応性重合体の製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59159828A true JPS59159828A (ja) | 1984-09-10 |
| JPH0149299B2 JPH0149299B2 (enrdf_load_stackoverflow) | 1989-10-24 |
Family
ID=12373375
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3295683A Granted JPS59159828A (ja) | 1983-03-02 | 1983-03-02 | 反応性重合体の製造法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59159828A (enrdf_load_stackoverflow) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2244491A (en) * | 1990-04-02 | 1991-12-04 | Etienne Honore Schacht | Conjugate compounds of polymers with other organic molecular entities. |
| JP2009540071A (ja) * | 2006-06-15 | 2009-11-19 | セル セラピューティクス インコーポレーテッド セーデ セコンダリア | ポリ−α−グルタミン酸およびその誘導体の製造方法 |
| GB2509972A (en) * | 2013-01-21 | 2014-07-23 | Gm Global Tech Operations Inc | Shift mechanism with shift finger having a damping member |
| US20170022301A1 (en) * | 2015-07-24 | 2017-01-26 | Bridgestone Corporation | Polymers functionalized with imine compounds containing a protected thiol group |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5718727A (en) * | 1980-07-07 | 1982-01-30 | Teijin Ltd | Reactive polymer and its preparation |
| JPS5730724A (en) * | 1980-07-31 | 1982-02-19 | Teijin Ltd | Polymer having disulfide bond in molecule and its preparation |
-
1983
- 1983-03-02 JP JP3295683A patent/JPS59159828A/ja active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5718727A (en) * | 1980-07-07 | 1982-01-30 | Teijin Ltd | Reactive polymer and its preparation |
| JPS5730724A (en) * | 1980-07-31 | 1982-02-19 | Teijin Ltd | Polymer having disulfide bond in molecule and its preparation |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2244491A (en) * | 1990-04-02 | 1991-12-04 | Etienne Honore Schacht | Conjugate compounds of polymers with other organic molecular entities. |
| JP2009540071A (ja) * | 2006-06-15 | 2009-11-19 | セル セラピューティクス インコーポレーテッド セーデ セコンダリア | ポリ−α−グルタミン酸およびその誘導体の製造方法 |
| GB2509972A (en) * | 2013-01-21 | 2014-07-23 | Gm Global Tech Operations Inc | Shift mechanism with shift finger having a damping member |
| US20170022301A1 (en) * | 2015-07-24 | 2017-01-26 | Bridgestone Corporation | Polymers functionalized with imine compounds containing a protected thiol group |
| US10077323B2 (en) * | 2015-07-24 | 2018-09-18 | Bridgestone Corporation | Polymers functionalized with imine compounds containing a protected thiol group |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0149299B2 (enrdf_load_stackoverflow) | 1989-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4385169A (en) | Reactive alpha amino acid polymer | |
| US5869466A (en) | Vitamin B12 mediated oral delivery systems for GCSF | |
| CA2187346C (en) | Receptor modulating agents and methods relating thereto | |
| JPS6112630A (ja) | 免疫毒素およびその製造法 | |
| JPS6121227B2 (enrdf_load_stackoverflow) | ||
| JPS6221000B2 (enrdf_load_stackoverflow) | ||
| KR20010085742A (ko) | 정밀한 길이의 폴리아미드 사슬, 그 제조방법 및 단백질결합체의 제조방법 | |
| JPH048411B2 (enrdf_load_stackoverflow) | ||
| JPH0383583A (ja) | アミロース―リゾチームハイブリッドと活性化糖およびその製造法 | |
| JP2007070277A5 (enrdf_load_stackoverflow) | ||
| JPS59159828A (ja) | 反応性重合体の製造法 | |
| EP3166644B1 (en) | Method of synthesising adcs using photocleavable linkers on solid support | |
| KR930003333B1 (ko) | 탄수화물 단위가 변형된 리보솜을 비활성화시키는 당단백질 성분을 함유하는 지속-작용성 면역독소의 제조방법 | |
| WO1991015242A1 (en) | Conjugate compounds of polymers with other organic molecular entities | |
| JPH0742316B2 (ja) | オシド単位の酸化およびシツフ塩基の形成により変性されたリボソ−ム不活性化糖タンパク、およびこの糖タンパクを含む生体内持続性免疫毒素 | |
| JPS6238368B2 (enrdf_load_stackoverflow) | ||
| JPH0149298B2 (enrdf_load_stackoverflow) | ||
| JPS6219770B2 (enrdf_load_stackoverflow) | ||
| Veronese et al. | Preparation and properties of monomethoxypoly (ethylene glycol)-modified enzymes for therapeutic applications | |
| EP0261225B1 (en) | Lectin complex and method and probe for making same | |
| JPH0338294B2 (enrdf_load_stackoverflow) | ||
| JPS62175500A (ja) | 修飾糖タンパク質、当該修飾糖タンパク質の製造方法、当該修飾糖タンパク質を含む免疫毒素および当該免疫毒素を有効成分として含む抗ガン剤組成物 | |
| JPS60168726A (ja) | 細胞毒性物質を結合した反応性高分子およびその製造法 | |
| JP2008285567A (ja) | 多分岐シクロデキストリン化合物、その製造方法、および標的指向性薬物送達システム用の薬物送達剤 | |
| Palacios et al. | Novel solid-phase synthesis of thiol-terminated-poly (α-amino acid)-drug conjugate |