ZA200201089B - Polypeptide dendrimers as unimolecular carriers of diagnostic imaging contrast agents, bioactive substances and drugs. - Google Patents
Polypeptide dendrimers as unimolecular carriers of diagnostic imaging contrast agents, bioactive substances and drugs. Download PDFInfo
- Publication number
- ZA200201089B ZA200201089B ZA200201089A ZA200201089A ZA200201089B ZA 200201089 B ZA200201089 B ZA 200201089B ZA 200201089 A ZA200201089 A ZA 200201089A ZA 200201089 A ZA200201089 A ZA 200201089A ZA 200201089 B ZA200201089 B ZA 200201089B
- Authority
- ZA
- South Africa
- Prior art keywords
- gly
- polypeptide
- orn
- bioactive
- dendrimer
- Prior art date
Links
- 239000000412 dendrimer Substances 0.000 title claims description 121
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 121
- 229920000736 dendritic polymer Polymers 0.000 title claims description 120
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 103
- 229920001184 polypeptide Polymers 0.000 title claims description 99
- 230000000975 bioactive effect Effects 0.000 title claims description 66
- 239000000969 carrier Substances 0.000 title claims description 37
- 239000000126 substance Substances 0.000 title claims description 35
- 239000003814 drug Substances 0.000 title claims description 19
- 229940079593 drug Drugs 0.000 title claims description 18
- 239000002872 contrast media Substances 0.000 title claims description 9
- 238000002059 diagnostic imaging Methods 0.000 title claims description 7
- 238000000034 method Methods 0.000 claims description 30
- 238000003786 synthesis reaction Methods 0.000 claims description 22
- 230000015572 biosynthetic process Effects 0.000 claims description 21
- 235000001014 amino acid Nutrition 0.000 claims description 18
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 235000018102 proteins Nutrition 0.000 claims description 15
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 15
- 108091034117 Oligonucleotide Proteins 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 13
- 239000000427 antigen Substances 0.000 claims description 12
- 102000036639 antigens Human genes 0.000 claims description 12
- 108091007433 antigens Proteins 0.000 claims description 12
- 150000001720 carbohydrates Chemical class 0.000 claims description 12
- 229920001542 oligosaccharide Polymers 0.000 claims description 12
- 150000002482 oligosaccharides Chemical class 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 230000001580 bacterial effect Effects 0.000 claims description 10
- 230000001413 cellular effect Effects 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 125000000524 functional group Chemical group 0.000 claims description 10
- 238000001415 gene therapy Methods 0.000 claims description 10
- 150000002632 lipids Chemical class 0.000 claims description 10
- 244000045947 parasite Species 0.000 claims description 10
- 230000003612 virological effect Effects 0.000 claims description 10
- 238000009833 condensation Methods 0.000 claims description 9
- 230000005494 condensation Effects 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 6
- 108090000790 Enzymes Proteins 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 238000009792 diffusion process Methods 0.000 claims description 3
- 230000001678 irradiating effect Effects 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000003384 imaging method Methods 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000007790 solid phase Substances 0.000 claims description 2
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 20
- 239000003550 marker Substances 0.000 claims 9
- 239000003242 anti bacterial agent Substances 0.000 claims 4
- 230000000840 anti-viral effect Effects 0.000 claims 4
- 229940088710 antibiotic agent Drugs 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 229940041181 antineoplastic drug Drugs 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 101100505076 Caenorhabditis elegans gly-2 gene Proteins 0.000 claims 1
- QLDKCICRJVPECT-UHFFFAOYSA-N N-L-ornithyl-glycine Natural products NCCCC(N)C(=O)NCC(O)=O QLDKCICRJVPECT-UHFFFAOYSA-N 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000012062 aqueous buffer Substances 0.000 claims 1
- 238000011534 incubation Methods 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 239000012047 saturated solution Substances 0.000 claims 1
- 229920000962 poly(amidoamine) Polymers 0.000 description 11
- 238000013459 approach Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000013522 chelant Substances 0.000 description 4
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000007071 enzymatic hydrolysis Effects 0.000 description 3
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 3
- 230000008570 general process Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- -1 poly(propyleneamine) Polymers 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 2
- 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 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- SENLDUJVTGGYIH-UHFFFAOYSA-N n-(2-aminoethyl)-3-[[3-(2-aminoethylamino)-3-oxopropyl]-[2-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]ethyl]amino]propanamide Chemical class NCCNC(=O)CCN(CCC(=O)NCCN)CCN(CCC(=O)NCCN)CCC(=O)NCCN SENLDUJVTGGYIH-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- HABAPWZXRLIZDL-UHFFFAOYSA-N 2-chloro-2-phenoxyacetic acid Chemical compound OC(=O)C(Cl)OC1=CC=CC=C1 HABAPWZXRLIZDL-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical class OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000000701 chemical imaging Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229940063718 lodine Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 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
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 239000000178 monomer 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
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006295 polythiol Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical class CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 108010004034 stable plasma protein solution Proteins 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- PCCVSPMFGIFTHU-UHFFFAOYSA-N tetracyanoquinodimethane Chemical compound N#CC(C#N)=C1C=CC(=C(C#N)C#N)C=C1 PCCVSPMFGIFTHU-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/641—Branched, dendritic or hypercomb peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1999FO000015A ITFO990015A1 (it) | 1999-07-23 | 1999-07-23 | "dendrimeri polipeptidici quali trasportatori unimolecolari di farmaci e sostanze biologicamente attive". |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200201089B true ZA200201089B (en) | 2003-07-30 |
Family
ID=11353680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200201089A ZA200201089B (en) | 1999-07-23 | 2002-02-07 | Polypeptide dendrimers as unimolecular carriers of diagnostic imaging contrast agents, bioactive substances and drugs. |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1200461A2 (ja) |
| JP (1) | JP2003506326A (ja) |
| CN (1) | CN1364171A (ja) |
| AU (1) | AU772167B2 (ja) |
| CA (1) | CA2380178A1 (ja) |
| HU (1) | HUP0201975A3 (ja) |
| IT (1) | ITFO990015A1 (ja) |
| NO (1) | NO20020333L (ja) |
| NZ (1) | NZ517231A (ja) |
| PL (1) | PL353273A1 (ja) |
| WO (1) | WO2001007469A2 (ja) |
| ZA (1) | ZA200201089B (ja) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR032941A1 (es) | 2001-03-05 | 2003-12-03 | Shell Int Research | Un procedimiento para preparar un aceite base lubricante y aceite base obtenido, con sus diversas utilizaciones |
| MY139353A (en) | 2001-03-05 | 2009-09-30 | Shell Int Research | Process to prepare a lubricating base oil and a gas oil |
| MY137259A (en) | 2001-03-05 | 2009-01-30 | Shell Int Research | Process to prepare a lubricating base oil and a gas oil. |
| WO2003037383A1 (en) * | 2001-10-29 | 2003-05-08 | The Dow Chemical Company | An antineoplastic- dendritic polymer drug delivery system |
| AU2003255058A1 (en) | 2002-07-18 | 2004-02-09 | Shell Internationale Research Maatschappij B.V. | Process to prepare a microcrystalline wax and a middle distillate fuel |
| EP1525890A1 (en) * | 2003-10-02 | 2005-04-27 | Complex Biosystems GmbH | Protein-Proteophore complexes |
| JP5401095B2 (ja) | 2005-11-17 | 2014-01-29 | ゾゲニクス インコーポレーティッド | 無針注射による粘性製剤の送達方法 |
| HUP0700782A3 (en) * | 2007-12-05 | 2009-11-30 | Biostatin Gyogyszerkutato Fejl | Novel peptides and amino acid derivatives, pharmaceutical compositions containing the same and use of the compounds |
| EP2756756B1 (en) | 2008-04-28 | 2016-01-06 | Zogenix, Inc. | Novel formulations for treatment of migraine |
| NZ591052A (en) * | 2008-08-05 | 2012-11-30 | Univ Queensland | Antigen-presenting scaffolds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995000540A1 (en) * | 1993-06-18 | 1995-01-05 | Robert Webber | Synthetic carrier and immunogen |
| EP1011736A2 (en) * | 1997-01-29 | 2000-06-28 | Nycomed Imaging As | Polymers |
-
1999
- 1999-07-23 IT IT1999FO000015A patent/ITFO990015A1/it unknown
-
2000
- 2000-07-21 CA CA002380178A patent/CA2380178A1/en not_active Abandoned
- 2000-07-21 WO PCT/EP2000/007022 patent/WO2001007469A2/en not_active Application Discontinuation
- 2000-07-21 CN CN00810769A patent/CN1364171A/zh active Pending
- 2000-07-21 PL PL00353273A patent/PL353273A1/xx not_active Application Discontinuation
- 2000-07-21 HU HU0201975A patent/HUP0201975A3/hu unknown
- 2000-07-21 AU AU62766/00A patent/AU772167B2/en not_active Ceased
- 2000-07-21 EP EP00949393A patent/EP1200461A2/en not_active Withdrawn
- 2000-07-21 NZ NZ517231A patent/NZ517231A/en unknown
- 2000-07-21 JP JP2001512552A patent/JP2003506326A/ja active Pending
-
2002
- 2002-01-22 NO NO20020333A patent/NO20020333L/no not_active Application Discontinuation
- 2002-02-07 ZA ZA200201089A patent/ZA200201089B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU6276600A (en) | 2001-02-13 |
| NO20020333D0 (no) | 2002-01-22 |
| JP2003506326A (ja) | 2003-02-18 |
| WO2001007469A3 (en) | 2001-05-10 |
| HUP0201975A3 (en) | 2002-11-28 |
| CN1364171A (zh) | 2002-08-14 |
| HUP0201975A2 (en) | 2002-10-28 |
| PL353273A1 (en) | 2003-11-03 |
| AU772167B2 (en) | 2004-04-08 |
| NZ517231A (en) | 2003-05-30 |
| EP1200461A2 (en) | 2002-05-02 |
| CA2380178A1 (en) | 2001-02-01 |
| ITFO990015A1 (it) | 2001-01-23 |
| WO2001007469A2 (en) | 2001-02-01 |
| NO20020333L (no) | 2002-01-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lyu et al. | Poly (amidoamine) dendrimers: Covalent and supramolecular synthesis | |
| ES2257672T3 (es) | Biomoleculas polimericas o excipientes de medicamentos de degradacion controlada y metodo de sintesis de dichos excipientes. | |
| Kono et al. | Preparation and cytotoxic activity of poly (ethylene glycol)-modified poly (amidoamine) dendrimers bearing adriamycin | |
| Medina et al. | Dendrimers as carriers for delivery of chemotherapeutic agents | |
| US5919442A (en) | Hyper comb-branched polymer conjugates | |
| Nanjwade et al. | Dendrimers: emerging polymers for drug-delivery systems | |
| Boas et al. | Dendrimers in drug research | |
| Satija et al. | Pharmaceutical and biomedical potential of surface engineered dendrimers | |
| WO1997006833A9 (en) | Hyper comb-branched polymer conjugates | |
| Villalonga-Barber et al. | Dendrimers as biopharmaceuticals: synthesis and properties | |
| ZA200202695B (en) | Manufacture of polyglutamate-therapeutic agent conjugates. | |
| Van Dongen et al. | PAMAM dendrimers as quantized building blocks for novel nanostructures | |
| ZA200201089B (en) | Polypeptide dendrimers as unimolecular carriers of diagnostic imaging contrast agents, bioactive substances and drugs. | |
| Tai et al. | A novel rapamycin-polymer conjugate based on a new poly (ethylene glycol) multiblock copolymer | |
| Lin et al. | Dendrimers in drug-delivery applications | |
| Jain et al. | Types of dendrimers | |
| WO2017206477A1 (zh) | 一种高分子ca4键合药物化合物及其制备方法 | |
| EP1675888A1 (en) | Cationic polymers having degradable crosslinks | |
| JP2022550901A (ja) | 核酸治療薬のための腫瘍標的化ポリペプチドナノ粒子送達システム | |
| JPH11124396A (ja) | 樹状ポリペプチド | |
| Sebestik et al. | Synthesis of dendrimers: Convergent and divergent approaches | |
| US8796234B2 (en) | Crosslinking branched molecule through thiol-disulfide exchange to form hydrogel | |
| KR20010069179A (ko) | 유전자 전달용 양이온성 리피드 및 그 제조방법 | |
| Das et al. | An overview of dendrimers and their biomedical applications | |
| Syed et al. | Dendrimers based drug delivery systems |