DE69602809T2 - Transportvehikel für Makromoleküle - Google Patents
Transportvehikel für MakromoleküleInfo
- Publication number
- DE69602809T2 DE69602809T2 DE69602809T DE69602809T DE69602809T2 DE 69602809 T2 DE69602809 T2 DE 69602809T2 DE 69602809 T DE69602809 T DE 69602809T DE 69602809 T DE69602809 T DE 69602809T DE 69602809 T2 DE69602809 T2 DE 69602809T2
- Authority
- DE
- Germany
- Prior art keywords
- hydrogen
- alkyl
- compounds according
- compounds
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229920002521 macromolecule Polymers 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 230000008685 targeting Effects 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000002091 cationic group Chemical group 0.000 claims description 5
- 108010090804 Streptavidin Proteins 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 15
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000003342 alkenyl group Chemical group 0.000 claims 3
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- AZAIVBIQGNIFJR-UHFFFAOYSA-M didecyl 1-methylpyridin-1-ium-3,5-dicarboxylate;iodide Chemical compound [I-].CCCCCCCCCCOC(=O)C1=CC(C(=O)OCCCCCCCCCC)=C[N+](C)=C1 AZAIVBIQGNIFJR-UHFFFAOYSA-M 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- 239000002502 liposome Substances 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 150000003904 phospholipids Chemical class 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000012202 endocytosis Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000000799 fusogenic effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000001243 protein synthesis Methods 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000002691 unilamellar liposome Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- TVDRYRJRVCTYOL-KTKRTIGZSA-N (z)-1-iodooctadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCI TVDRYRJRVCTYOL-KTKRTIGZSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-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
- RGCKJSPKMTWLLX-UHFFFAOYSA-N 3-iodopropylbenzene Chemical compound ICCCC1=CC=CC=C1 RGCKJSPKMTWLLX-UHFFFAOYSA-N 0.000 description 1
- QIWKNZFEJGPNFM-UHFFFAOYSA-M 4-dodecyl-1-(3-phenylpropyl)pyridin-1-ium;iodide Chemical compound [I-].C1=CC(CCCCCCCCCCCC)=CC=[N+]1CCCC1=CC=CC=C1 QIWKNZFEJGPNFM-UHFFFAOYSA-M 0.000 description 1
- FVZKYRYEWBZUTR-UHFFFAOYSA-N 4-dodecylpyridine Chemical compound CCCCCCCCCCCCC1=CC=NC=C1 FVZKYRYEWBZUTR-UHFFFAOYSA-N 0.000 description 1
- BREMRXDAQBICTI-UHFFFAOYSA-M 4-heptatriacontan-19-yl-1-methylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCC(CCCCCCCCCCCCCCCCCC)C1=CC=[N+](C)C=C1 BREMRXDAQBICTI-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- KUHDCQYBPHGFKV-CITAKDKDSA-N [[(2r,3s,4r,5r)-5-[6-(butanoylamino)purin-9-yl]-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3r)-3-hydroxy-2,2-dimethyl-4-oxo-4-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butyl] hydrogen phosphate Chemical compound C1=NC=2C(NC(=O)CCC)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)[C@@H](OP(O)(O)=O)[C@H]1O KUHDCQYBPHGFKV-CITAKDKDSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003947 protein internalization Effects 0.000 description 1
- BJDYCCHRZIFCGN-UHFFFAOYSA-N pyridin-1-ium;iodide Chemical compound I.C1=CC=NC=C1 BJDYCCHRZIFCGN-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
- C07D213/20—Quaternary compounds thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Separation, Recovery Or Treatment Of Waste Materials Containing Plastics (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Treatment Of Sludge (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Claims (18)
1. Verbindungen mit der allgemeinen Formel I
in der:
R&sub1; eine (C&sub1;-C&sub5;)Alkyl-, Ar(alkyl)- oder eine Alkyl-Gruppe mit einer
kationischen funktionellen Gruppe wie (C&sub1;-C&sub5;) ist; oder in der R&sub1; (C&sub1;-
C&sub5;-Alkylen) R&sub5; ist, worin R&sub5; eine Struktur mit der allgemeinen Formel I
ohne R, ist,
X ein Halogenid-Gegenion ist, das ausgewählt ist aus Cl&supmin;, I&supmin;, Br&supmin;; und in
der
R&sub3; Wasserstoff ist und R&sub2; und R&sub4; gleich oder verschieden sind und
ausgewählt sind aus der Gruppe, die verzweigtes oder lineares (C&sub1;&sub0;-
C&sub2;&sub0;)Alkyl, ein mono- oder polyungesättigtes (C&sub1;&sub0;-C&sub2;&sub0;)Alkenyl, O=C-O-
Alkyl,
-Alkyl oder Ar(alkyl) aufweist,
oder in der R&sub2; und R&sub4; Wasserstoff sind und R&sub3; -CH(R&sub5;)&sub2; ist, wobei R&sub5;
(C&sub1;&sub0;-C&sub2;&sub0;)Alkyl, mono- oder polyungesättigtes (C&sub1;&sub0;-C&sub2;&sub0;)Alkenyl, O=C-O-
Alkyl,
-Alkyl oder Aralkyl aufweist,
unter Ausschluß der Verbindungen mit der allgemeinen Formel I, in
denen R&sub1; CH&sub3; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub6;H&sub3;&sub3;)&sub2;CH ist und X
alle aufgeführten Gegenionen (Cl&supmin;, I&supmin;, Br&supmin;) ist, und unter Ausschluß der
Verbindungen, in denen R&sub1; CH&sub3; ist, R&sub2; und R&sub4; C&sub1;&sub6;H&sub3;&sub3;-O-C(O) sind, R&sub3;
Wasserstoff ist und X alle aufgeführten Gegenionen (Cl&supmin;, I&supmin;, Br&supmin;) ist, und
3,5-Bis [(decyloxy)-carbonyl]-1-methyl-pyridinium-iodid.
2. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub8;H&sub3;&sub7;)&sub2;CH ist und X Cl&supmin;, Br&supmin;,
I&supmin; ist.
3. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub8;H&sub3;&sub5;)&sub2;CH ist und X Cl&supmin;, Br&supmin;,
I&supmin; ist.
4. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
(CH&sub2;)&sub4;- N&spplus;(CH&sub3;)&sub3; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub8;H&sub3;&sub5;)&sub2;CH ist und
X Cl&supmin;, Br&supmin;, I&supmin; ist.
5. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R&sub2; und R&sub4; C&sub1;&sub8;H&sub3;&sub7;-O-C(O) sind, R&sub3; Wasserstoff ist und X Cl&supmin;,
Br&supmin;, I&supmin; ist.
6. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R&sub2; und R&sub4; R&sub5;-O-C(O) sind, worin R&sub5; eine gesättigte,
aliphatische C&sub1;&sub0;-C&sub2;&sub0;-Kette ist, R&sub3; Wasserstoff ist und X Cl&supmin;, Br&supmin;, I&supmin; ist.
7. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R, und R&sub4; nicht gleich sind und jedes eine Gruppe mit der
Formel R&sub5;-O-C(O) darstellt, worin R&sub5; ein C&sub1;&sub0;-C&sub2;&sub0;-Alkyl ist, R&sub3;
Wasserstoff ist und X Cl&supmin;, Br&supmin;, I&supmin; ist.
8. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
CH&sub3; ist, R&sub3; eine Gruppe mit der Formel R&sub5;-O-C(O) ist, worin R&sub5; ein
C&sub1;&sub0;-C&sub2;&sub0;-Alkyl ist, R&sub2; und R&sub4; Wasserstoff sind und X Cl&supmin;, Br&supmin; oder I&supmin; ist.
9. Verbindungen nach Anspruch 8, dadurch gekennzeichnet, daß R&sub5;
C&sub1;&sub6;H&sub3;&sub3; ist.
10. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
(CH&sub2;)n-C&sub6;H&sub5; ist, worin n = 3-6, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; Alkyl
oder Alkenyl ist und X Cl&supmin;, Br&supmin; oder I&supmin; ist.
11. Verbindung nach Anspruch 10, dadurch gekennzeichnet, daß R&sub1;
(CH&sub2;)&sub3;-C&sub6;H&sub5; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; n-C&sub1;&sub2;H&sub2;&sub5; ist und X Cl&supmin;,
Br&supmin; oder I&supmin; ist.
12. Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß R&sub1;
(CH&sub2;)&sub4; ist, R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub8;H&sub3;&sub5;)&sub2;CH ist, X Cl&supmin;, Br&supmin;, I&supmin;
ist, und R&sub5; die Gruppe mit der allgemeinen Formel I ist, die über R&sub1;
gebunden ist, worin R&sub2; und R&sub4; Wasserstoff sind, R&sub3; (C&sub1;&sub8;H&sub3;&sub5;)&sub2;CH ist und
X Cl&supmin;, Br&supmin;, I&supmin; ist.
13. Verbindungen nach einem der vorangehenden Ansprüche zur
Verwendung als ein Hilfsmittel zum Einführen von Makromolekülen in
Zellen.
14. Zusammensetzung zur Einführung von Makromolekülen in Zellen,
die Vesikel oder eine andere Art von mittels mindestens einer
Verbindung gemäß einem der vorangehenden Ansprüche gebildetem Aggregat
in einem Lösungsmittel aufweist.
15. Zusammensetzung nach Anspruch 14, dadurch gekennzeichnet, daß
mindestens ein Makromolekül in die Vesikel inkorporiert und/oder an
die Vesikel gebunden ist.
16. Zusammensetzung nach Anspruch 14 oder 15, dadurch
gekennzeichnet, daß außerdem mindestens ein Zielfindungsmolekül an die
Vesikel gebunden ist.
17. Zusammensetzung nach Anspruch 15, dadurch gekennzeichnet, daß
Zielfindungsmolekül ein Antikörper ist.
18. Zusammensetzung nach Anspruch 16, dadurch gekennzeichnet, daß
der Antikörper radioaktiv markiert oder mit Streptavidin markiert ist.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL1000884A NL1000884C2 (nl) | 1995-07-25 | 1995-07-25 | Transportvehikels voor macromoleculen. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69602809D1 DE69602809D1 (de) | 1999-07-15 |
| DE69602809T2 true DE69602809T2 (de) | 1999-12-16 |
Family
ID=19761371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69602809T Expired - Lifetime DE69602809T2 (de) | 1995-07-25 | 1996-07-24 | Transportvehikel für Makromoleküle |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5853694A (de) |
| EP (1) | EP0755924B1 (de) |
| JP (1) | JP4771564B2 (de) |
| AT (1) | ATE181065T1 (de) |
| CA (1) | CA2181841C (de) |
| DE (1) | DE69602809T2 (de) |
| DK (1) | DK0755924T3 (de) |
| ES (1) | ES2137623T3 (de) |
| GR (1) | GR3031200T3 (de) |
| NL (1) | NL1000884C2 (de) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR19990025725A (ko) * | 1997-09-13 | 1999-04-06 | 윤종용 | 파장 분할 다중 통신용 광섬유 및 그 제조 방법 |
| WO1999018792A1 (en) * | 1997-10-10 | 1999-04-22 | Johns Hopkins University | Gene delivery compositions and methods |
| US7294511B2 (en) | 2001-03-22 | 2007-11-13 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| US6936469B2 (en) | 2001-03-22 | 2005-08-30 | Chromos Molecular Systems Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| WO2002076508A1 (en) * | 2001-03-22 | 2002-10-03 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| US20030186390A1 (en) * | 2001-03-22 | 2003-10-02 | De Jong Gary | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| EP1254896A1 (de) * | 2001-05-03 | 2002-11-06 | Applied NanoSystems B.V. | Kationische Amphiphile, Verfahren und Methoden zur Transfektion |
| WO2003093469A2 (en) * | 2002-05-01 | 2003-11-13 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| US7330851B2 (en) * | 2003-08-18 | 2008-02-12 | Eaglehawk, Limited | Data security through dissembly of data elements or connections between elements |
| NL1027311C2 (nl) * | 2004-10-21 | 2006-05-01 | Synvolux Ip B V | Vehikel voor transport van een DNA-modificerend enzym naar een genoom. |
| NL1027479C2 (nl) * | 2004-10-21 | 2006-05-01 | Synvolux Ip B V | Bescherming van biologisch actieve moleculen met behulp van amphifielen. |
| EP2200586B1 (de) * | 2007-09-07 | 2019-11-13 | Synvolux IP B.V. | Verbesserte liposome und ihre verwendung |
| GB0724253D0 (en) | 2007-12-12 | 2008-01-30 | Fermentas Uab | Transfection reagent |
| DE102008032594A1 (de) | 2008-07-11 | 2010-01-14 | Qiagen Gmbh | Transfektionslösung |
| GB0917792D0 (en) | 2009-10-12 | 2009-11-25 | Fermentas Uab | Delivery agent |
| US9856456B2 (en) | 2009-10-12 | 2018-01-02 | Thermo Fisher Scientific Baltics Uab | Delivery agent |
| JP5514368B2 (ja) * | 2011-12-21 | 2014-06-04 | キリンホールディングス株式会社 | 細胞内に導入するための温度感受性蛍光プローブ |
| JP6666673B2 (ja) * | 2015-09-07 | 2020-03-18 | キリンホールディングス株式会社 | 細胞内送達ベヒクル |
| NL2026569B1 (en) | 2020-09-29 | 2022-05-30 | Crm Therapeutics B V | Target mediated endocytotic drug delivery |
| EP4221757A1 (de) | 2020-09-29 | 2023-08-09 | CRM Therapeutics B.V. | Zielvermittelte endozytotische wirkstofffreisetzung |
| NL2027601B1 (en) | 2021-02-19 | 2022-09-19 | Crm Therapeutics B V | Target mediated endocytotic drug delivery |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4824850A (en) * | 1982-05-18 | 1989-04-25 | University Of Florida | Brain-specific drug delivery |
| EP0277270B1 (de) * | 1986-08-07 | 1996-12-27 | MEDICEChem.-Pharm. Fabrik Pütter GmbH & Co. KG | N-alkylierte quartäre stickstoffhaltige Heterozyklen, Verfahren zu deren Herstellung und deren Verwendung in Arzneimitteln |
| US4957785A (en) * | 1988-03-25 | 1990-09-18 | Fornadley Michael R | Light transmissive stone structure and method for making same |
-
1995
- 1995-07-25 NL NL1000884A patent/NL1000884C2/nl active Search and Examination
-
1996
- 1996-07-23 CA CA002181841A patent/CA2181841C/en not_active Expired - Lifetime
- 1996-07-24 AT AT96202095T patent/ATE181065T1/de active
- 1996-07-24 DK DK96202095T patent/DK0755924T3/da active
- 1996-07-24 US US08/686,045 patent/US5853694A/en not_active Expired - Lifetime
- 1996-07-24 ES ES96202095T patent/ES2137623T3/es not_active Expired - Lifetime
- 1996-07-24 EP EP96202095A patent/EP0755924B1/de not_active Expired - Lifetime
- 1996-07-24 DE DE69602809T patent/DE69602809T2/de not_active Expired - Lifetime
- 1996-07-25 JP JP22918696A patent/JP4771564B2/ja not_active Expired - Fee Related
-
1999
- 1999-09-09 GR GR990402294T patent/GR3031200T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US5853694A (en) | 1998-12-29 |
| JP4771564B2 (ja) | 2011-09-14 |
| DK0755924T3 (da) | 1999-11-29 |
| EP0755924A1 (de) | 1997-01-29 |
| DE69602809D1 (de) | 1999-07-15 |
| ATE181065T1 (de) | 1999-06-15 |
| EP0755924B1 (de) | 1999-06-09 |
| JPH09285290A (ja) | 1997-11-04 |
| GR3031200T3 (en) | 1999-12-31 |
| ES2137623T3 (es) | 1999-12-16 |
| CA2181841A1 (en) | 1997-01-26 |
| CA2181841C (en) | 2008-01-08 |
| NL1000884C2 (nl) | 1997-01-28 |
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