AU3724495A - Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents - Google Patents
Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agentsInfo
- Publication number
- AU3724495A AU3724495A AU37244/95A AU3724495A AU3724495A AU 3724495 A AU3724495 A AU 3724495A AU 37244/95 A AU37244/95 A AU 37244/95A AU 3724495 A AU3724495 A AU 3724495A AU 3724495 A AU3724495 A AU 3724495A
- Authority
- AU
- Australia
- Prior art keywords
- hbegf
- conjugate
- dna
- cells
- polypeptide
- 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.)
- Abandoned
Links
- 239000003795 chemical substances by application Substances 0.000 title claims description 149
- 230000027455 binding Effects 0.000 title claims description 92
- 239000003102 growth factor Substances 0.000 title claims description 28
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 title claims description 21
- 229920000669 heparin Polymers 0.000 title claims description 19
- 229960002897 heparin Drugs 0.000 title claims description 19
- 230000010005 growth-factor like effect Effects 0.000 title claims description 7
- 210000004027 cell Anatomy 0.000 claims description 241
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 175
- 108010084592 Saporins Proteins 0.000 claims description 166
- 239000013612 plasmid Substances 0.000 claims description 163
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 156
- 229920001184 polypeptide Polymers 0.000 claims description 148
- 102000005962 receptors Human genes 0.000 claims description 115
- 238000000034 method Methods 0.000 claims description 104
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 91
- 235000001014 amino acid Nutrition 0.000 claims description 83
- 108020001507 fusion proteins Proteins 0.000 claims description 82
- 102000037865 fusion proteins Human genes 0.000 claims description 82
- 239000012634 fragment Substances 0.000 claims description 80
- 230000014509 gene expression Effects 0.000 claims description 80
- 150000007523 nucleic acids Chemical group 0.000 claims description 76
- 102000039446 nucleic acids Human genes 0.000 claims description 74
- 108020004707 nucleic acids Proteins 0.000 claims description 74
- 150000001413 amino acids Chemical class 0.000 claims description 68
- 239000000126 substance Substances 0.000 claims description 51
- 125000003729 nucleotide group Chemical group 0.000 claims description 50
- 239000000872 buffer Substances 0.000 claims description 49
- 239000002773 nucleotide Substances 0.000 claims description 49
- 108090000829 Ribosome Inactivating Proteins Proteins 0.000 claims description 46
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 45
- 235000018417 cysteine Nutrition 0.000 claims description 44
- 239000000758 substrate Substances 0.000 claims description 44
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- 229940127089 cytotoxic agent Drugs 0.000 claims description 42
- 239000002254 cytotoxic agent Substances 0.000 claims description 42
- 230000001580 bacterial effect Effects 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 230000028327 secretion Effects 0.000 claims description 22
- 241000238631 Hexapoda Species 0.000 claims description 18
- -1 OmpT Proteins 0.000 claims description 18
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 18
- 238000003780 insertion Methods 0.000 claims description 18
- 230000037431 insertion Effects 0.000 claims description 18
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 18
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 16
- 108091005804 Peptidases Proteins 0.000 claims description 15
- 239000004365 Protease Substances 0.000 claims description 15
- 230000035755 proliferation Effects 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 239000012539 chromatography resin Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 239000006166 lysate Substances 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- 239000013604 expression vector Substances 0.000 claims description 11
- 238000005277 cation exchange chromatography Methods 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 102000002260 Alkaline Phosphatase Human genes 0.000 claims description 8
- 108020004774 Alkaline Phosphatase Proteins 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 230000004963 pathophysiological condition Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 102000003908 Cathepsin D Human genes 0.000 claims description 6
- 108090000258 Cathepsin D Proteins 0.000 claims description 6
- 108090000190 Thrombin Proteins 0.000 claims description 6
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- 238000005571 anion exchange chromatography Methods 0.000 claims description 6
- 239000004202 carbamide Substances 0.000 claims description 6
- 238000001415 gene therapy Methods 0.000 claims description 6
- 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 claims description 6
- 230000005937 nuclear translocation Effects 0.000 claims description 6
- 102220065898 rs794726925 Human genes 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 6
- 238000001542 size-exclusion chromatography Methods 0.000 claims description 6
- 229960004072 thrombin Drugs 0.000 claims description 6
- 108090000631 Trypsin Proteins 0.000 claims description 5
- 102000004142 Trypsin Human genes 0.000 claims description 5
- 239000012588 trypsin Substances 0.000 claims description 5
- 102000004225 Cathepsin B Human genes 0.000 claims description 4
- 108090000712 Cathepsin B Proteins 0.000 claims description 4
- 108010036176 Melitten Proteins 0.000 claims description 4
- 210000002919 epithelial cell Anatomy 0.000 claims description 4
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 108010051696 Growth Hormone Proteins 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 102000004877 Insulin Human genes 0.000 claims description 3
- 108090000787 Subtilisin Proteins 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 239000000122 growth hormone Substances 0.000 claims description 3
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- VDXZNPDIRNWWCW-UHFFFAOYSA-N melitten Chemical compound NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-UHFFFAOYSA-N 0.000 claims description 3
- 101150050446 pelB gene Proteins 0.000 claims description 3
- 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 claims description 2
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 claims description 2
- 210000001339 epidermal cell Anatomy 0.000 claims description 2
- 230000002934 lysing effect Effects 0.000 claims description 2
- 101150040383 pel2 gene Proteins 0.000 claims description 2
- 101150009573 phoA gene Proteins 0.000 claims description 2
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 2
- 239000003797 essential amino acid Substances 0.000 claims 2
- 235000020776 essential amino acid Nutrition 0.000 claims 2
- 102000018997 Growth Hormone Human genes 0.000 claims 1
- 108010079246 OMPA outer membrane proteins Proteins 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 102220080600 rs797046116 Human genes 0.000 claims 1
- 102100033762 Proheparin-binding EGF-like growth factor Human genes 0.000 description 353
- 108020004414 DNA Proteins 0.000 description 284
- 108090000623 proteins and genes Proteins 0.000 description 222
- 102000004169 proteins and genes Human genes 0.000 description 161
- 235000018102 proteins Nutrition 0.000 description 157
- 108020003175 receptors Proteins 0.000 description 106
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 93
- 229940024606 amino acid Drugs 0.000 description 74
- 230000000694 effects Effects 0.000 description 59
- 108091007494 Nucleic acid- binding domains Proteins 0.000 description 57
- 102100036202 Serum amyloid P-component Human genes 0.000 description 53
- 239000013598 vector Substances 0.000 description 51
- 241000588724 Escherichia coli Species 0.000 description 48
- 108020004705 Codon Proteins 0.000 description 47
- 238000002360 preparation method Methods 0.000 description 47
- 239000011780 sodium chloride Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 42
- 230000021615 conjugation Effects 0.000 description 38
- 108091034117 Oligonucleotide Proteins 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 33
- 230000001472 cytotoxic effect Effects 0.000 description 33
- 239000003446 ligand Substances 0.000 description 32
- 239000000047 product Substances 0.000 description 32
- 230000014616 translation Effects 0.000 description 30
- 238000011282 treatment Methods 0.000 description 30
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 29
- 230000003321 amplification Effects 0.000 description 29
- 238000003199 nucleic acid amplification method Methods 0.000 description 29
- 150000001875 compounds Chemical class 0.000 description 28
- 231100000433 cytotoxic Toxicity 0.000 description 28
- 230000000692 anti-sense effect Effects 0.000 description 27
- 239000002243 precursor Substances 0.000 description 27
- 238000013518 transcription Methods 0.000 description 26
- 230000035897 transcription Effects 0.000 description 26
- 125000003275 alpha amino acid group Chemical group 0.000 description 25
- 238000007792 addition Methods 0.000 description 24
- 238000003556 assay Methods 0.000 description 24
- 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 23
- 230000001939 inductive effect Effects 0.000 description 23
- 239000000463 material Substances 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 238000001243 protein synthesis Methods 0.000 description 21
- 108091026890 Coding region Proteins 0.000 description 20
- 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 20
- 102220629935 Disintegrin and metalloproteinase domain-containing protein 19_G4S_mutation Human genes 0.000 description 19
- 229920002684 Sepharose Polymers 0.000 description 19
- 230000004071 biological effect Effects 0.000 description 19
- 231100000135 cytotoxicity Toxicity 0.000 description 19
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 19
- 230000004663 cell proliferation Effects 0.000 description 18
- 230000003013 cytotoxicity Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 125000003396 thiol group Chemical group [H]S* 0.000 description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 16
- 230000003834 intracellular effect Effects 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 14
- 102000001301 EGF receptor Human genes 0.000 description 14
- 108060006698 EGF receptor Proteins 0.000 description 14
- 102000035195 Peptidases Human genes 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 108090000994 Catalytic RNA Proteins 0.000 description 13
- 102000053642 Catalytic RNA Human genes 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 230000003993 interaction Effects 0.000 description 13
- 108091092562 ribozyme Proteins 0.000 description 13
- 231100000331 toxic Toxicity 0.000 description 13
- 230000002588 toxic effect Effects 0.000 description 13
- 238000001262 western blot Methods 0.000 description 13
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 12
- 108010039491 Ricin Proteins 0.000 description 12
- 238000010276 construction Methods 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 241000701447 unidentified baculovirus Species 0.000 description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 11
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 108020001756 ligand binding domains Proteins 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 230000009466 transformation Effects 0.000 description 11
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 10
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 10
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 208000037803 restenosis Diseases 0.000 description 10
- 241000894007 species Species 0.000 description 10
- 239000003053 toxin Substances 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- 101000871708 Homo sapiens Proheparin-binding EGF-like growth factor Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 150000004032 porphyrins Chemical class 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 231100000765 toxin Toxicity 0.000 description 9
- 108700012359 toxins Proteins 0.000 description 9
- 108010066676 Abrin Proteins 0.000 description 8
- 101710137500 T7 RNA polymerase Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 108010005774 beta-Galactosidase Proteins 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000030833 cell death Effects 0.000 description 8
- 230000010261 cell growth Effects 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 238000002784 cytotoxicity assay Methods 0.000 description 8
- 231100000263 cytotoxicity test Toxicity 0.000 description 8
- 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 8
- 229940079593 drug Drugs 0.000 description 8
- 238000001502 gel electrophoresis Methods 0.000 description 8
- 108010045383 histidyl-glycyl-glutamic acid Proteins 0.000 description 8
- 102000043417 human HBEGF Human genes 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 238000010369 molecular cloning Methods 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000010076 replication Effects 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 108010054278 Lac Repressors Proteins 0.000 description 7
- NDYNTQWSJLPEMK-WDSKDSINSA-N Met-Cys Chemical group CSCC[C@H](N)C(=O)N[C@@H](CS)C(O)=O NDYNTQWSJLPEMK-WDSKDSINSA-N 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 102100037681 Protein FEV Human genes 0.000 description 7
- 240000003946 Saponaria officinalis Species 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 238000000099 in vitro assay Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 230000002297 mitogenic effect Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 7
- BYXHQQCXAJARLQ-ZLUOBGJFSA-N Ala-Ala-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O BYXHQQCXAJARLQ-ZLUOBGJFSA-N 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 102000009661 Repressor Proteins Human genes 0.000 description 6
- 108091081021 Sense strand Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000011543 agarose gel Substances 0.000 description 6
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 6
- 238000001516 cell proliferation assay Methods 0.000 description 6
- 210000000805 cytoplasm Anatomy 0.000 description 6
- 239000002619 cytotoxin Substances 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 238000004925 denaturation Methods 0.000 description 6
- 230000036425 denaturation Effects 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 239000012139 lysis buffer Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 6
- 101150115693 ompA gene Proteins 0.000 description 6
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 238000002741 site-directed mutagenesis Methods 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- 238000011144 upstream manufacturing Methods 0.000 description 6
- NKDFYOWSKOHCCO-YPVLXUMRSA-N 20-hydroxyecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)(O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 NKDFYOWSKOHCCO-YPVLXUMRSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 5
- 101800003838 Epidermal growth factor Proteins 0.000 description 5
- XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 101710198166 Protein FEV Proteins 0.000 description 5
- 239000012614 Q-Sepharose Substances 0.000 description 5
- 108020004511 Recombinant DNA Proteins 0.000 description 5
- 108010034634 Repressor Proteins Proteins 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 238000000137 annealing Methods 0.000 description 5
- 108010062796 arginyllysine Proteins 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 210000001163 endosome Anatomy 0.000 description 5
- 238000000855 fermentation Methods 0.000 description 5
- 230000004151 fermentation Effects 0.000 description 5
- 239000002596 immunotoxin Substances 0.000 description 5
- 238000005462 in vivo assay Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000001322 periplasm Anatomy 0.000 description 5
- 108700028325 pokeweed antiviral Proteins 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 238000003259 recombinant expression Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 108010036211 5-HT-moduline Proteins 0.000 description 4
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 4
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 4
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 4
- 108020005544 Antisense RNA Proteins 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 4
- WTNLLMQAFPOCTJ-GARJFASQSA-N Cys-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CS)N)C(=O)O WTNLLMQAFPOCTJ-GARJFASQSA-N 0.000 description 4
- JUUMIGUJJRFQQR-KKUMJFAQSA-N Cys-Lys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)O JUUMIGUJJRFQQR-KKUMJFAQSA-N 0.000 description 4
- 108010017826 DNA Polymerase I Proteins 0.000 description 4
- 102000004594 DNA Polymerase I Human genes 0.000 description 4
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 4
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 4
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 4
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 4
- 108010053187 Diphtheria Toxin Proteins 0.000 description 4
- 102000016607 Diphtheria Toxin Human genes 0.000 description 4
- 101150007667 FPS2 gene Proteins 0.000 description 4
- APHGWLWMOXGZRL-DCAQKATOSA-N Glu-Glu-His Chemical compound N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O APHGWLWMOXGZRL-DCAQKATOSA-N 0.000 description 4
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 4
- QSVCIFZPGLOZGH-WDSKDSINSA-N Gly-Glu-Ser Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QSVCIFZPGLOZGH-WDSKDSINSA-N 0.000 description 4
- CLNSYANKYVMZNM-UWVGGRQHSA-N Gly-Lys-Arg Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CLNSYANKYVMZNM-UWVGGRQHSA-N 0.000 description 4
- KBBFOULZCHWGJX-KBPBESRZSA-N Gly-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)CN)O KBBFOULZCHWGJX-KBPBESRZSA-N 0.000 description 4
- HAPWZEVRQYGLSG-IUCAKERBSA-N His-Gly-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O HAPWZEVRQYGLSG-IUCAKERBSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- NTRAGDHVSGKUSF-AVGNSLFASA-N Leu-Arg-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NTRAGDHVSGKUSF-AVGNSLFASA-N 0.000 description 4
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 241000219470 Mirabilis Species 0.000 description 4
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 4
- PTWIYDNFWPXQSD-GARJFASQSA-N Ser-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N)C(=O)O PTWIYDNFWPXQSD-GARJFASQSA-N 0.000 description 4
- 241000256251 Spodoptera frugiperda Species 0.000 description 4
- IJGPOONOTBNTFS-GVXVVHGQSA-N Val-Lys-Glu Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O IJGPOONOTBNTFS-GVXVVHGQSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 4
- 235000011130 ammonium sulphate Nutrition 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 238000012230 antisense oligonucleotides Methods 0.000 description 4
- 101150042295 arfA gene Proteins 0.000 description 4
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000005341 cation exchange Methods 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000003184 complementary RNA Substances 0.000 description 4
- 229930191339 dianthin Natural products 0.000 description 4
- 229940116977 epidermal growth factor Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 108010036413 histidylglycine Proteins 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 229930027917 kanamycin Natural products 0.000 description 4
- 229960000318 kanamycin Drugs 0.000 description 4
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 4
- 229930182823 kanamycin A Natural products 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- 108010009298 lysylglutamic acid Proteins 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 101150087557 omcB gene Proteins 0.000 description 4
- 230000001991 pathophysiological effect Effects 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 210000001995 reticulocyte Anatomy 0.000 description 4
- 210000003705 ribosome Anatomy 0.000 description 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- FUSNMLFNXJSCDI-UHFFFAOYSA-N tolnaftate Chemical compound C=1C=C2C=CC=CC2=CC=1OC(=S)N(C)C1=CC=CC(C)=C1 FUSNMLFNXJSCDI-UHFFFAOYSA-N 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 239000012581 transferrin Substances 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- FSHURBQASBLAPO-WDSKDSINSA-N Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)N FSHURBQASBLAPO-WDSKDSINSA-N 0.000 description 3
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 3
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 3
- XRLOBFSLPCHYLQ-ULQDDVLXSA-N Arg-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O XRLOBFSLPCHYLQ-ULQDDVLXSA-N 0.000 description 3
- BZMWJLLUAKSIMH-FXQIFTODSA-N Asn-Glu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BZMWJLLUAKSIMH-FXQIFTODSA-N 0.000 description 3
- DWOSGXZMLQNDBN-FXQIFTODSA-N Asp-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CS)C(=O)O DWOSGXZMLQNDBN-FXQIFTODSA-N 0.000 description 3
- XMKXONRMGJXCJV-LAEOZQHASA-N Asp-Val-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XMKXONRMGJXCJV-LAEOZQHASA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 102000000844 Cell Surface Receptors Human genes 0.000 description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 description 3
- 101710112752 Cytotoxin Proteins 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 230000004544 DNA amplification Effects 0.000 description 3
- 230000006820 DNA synthesis Effects 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101150051414 FPS1 gene Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 3
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 3
- WZZSKAJIHTUUSG-ACZMJKKPSA-N Glu-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O WZZSKAJIHTUUSG-ACZMJKKPSA-N 0.000 description 3
- FLLRAEJOLZPSMN-CIUDSAMLSA-N Glu-Asn-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FLLRAEJOLZPSMN-CIUDSAMLSA-N 0.000 description 3
- CCBIBMKQNXHNIN-ZETCQYMHSA-N Gly-Leu-Gly Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CCBIBMKQNXHNIN-ZETCQYMHSA-N 0.000 description 3
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 101001083798 Homo sapiens Hepatoma-derived growth factor Proteins 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 3
- DUBAVOVZNZKEQQ-AVGNSLFASA-N Leu-Arg-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CCCN=C(N)N DUBAVOVZNZKEQQ-AVGNSLFASA-N 0.000 description 3
- DLCOFDAHNMMQPP-SRVKXCTJSA-N Leu-Asp-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DLCOFDAHNMMQPP-SRVKXCTJSA-N 0.000 description 3
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 3
- QPXBPQUGXHURGP-UWVGGRQHSA-N Leu-Gly-Met Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CCSC)C(=O)O)N QPXBPQUGXHURGP-UWVGGRQHSA-N 0.000 description 3
- MJTOYIHCKVQICL-ULQDDVLXSA-N Leu-Met-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N MJTOYIHCKVQICL-ULQDDVLXSA-N 0.000 description 3
- JDBQSGMJBMPNFT-AVGNSLFASA-N Leu-Pro-Val Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O JDBQSGMJBMPNFT-AVGNSLFASA-N 0.000 description 3
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 3
- 239000006137 Luria-Bertani broth Substances 0.000 description 3
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 3
- NKKFVJRLCCUJNA-QWRGUYRKSA-N Lys-Gly-Lys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN NKKFVJRLCCUJNA-QWRGUYRKSA-N 0.000 description 3
- ZJWIXBZTAAJERF-IHRRRGAJSA-N Lys-Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N ZJWIXBZTAAJERF-IHRRRGAJSA-N 0.000 description 3
- NYTDJEZBAAFLLG-IHRRRGAJSA-N Lys-Val-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(O)=O NYTDJEZBAAFLLG-IHRRRGAJSA-N 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 3
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 108091027981 Response element Proteins 0.000 description 3
- WUXCHQZLUHBSDJ-LKXGYXEUSA-N Ser-Thr-Asp Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC(O)=O)C(O)=O WUXCHQZLUHBSDJ-LKXGYXEUSA-N 0.000 description 3
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 3
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 3
- OJRNZRROAIAHDL-LKXGYXEUSA-N Thr-Asn-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OJRNZRROAIAHDL-LKXGYXEUSA-N 0.000 description 3
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 3
- STUAPCLEDMKXKL-LKXGYXEUSA-N Thr-Ser-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O STUAPCLEDMKXKL-LKXGYXEUSA-N 0.000 description 3
- 102000004338 Transferrin Human genes 0.000 description 3
- 108090000901 Transferrin Proteins 0.000 description 3
- 108010021119 Trichosanthin Proteins 0.000 description 3
- QNJYPWZACBACER-KKUMJFAQSA-N Tyr-Asp-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O QNJYPWZACBACER-KKUMJFAQSA-N 0.000 description 3
- 102000003425 Tyrosinase Human genes 0.000 description 3
- 108060008724 Tyrosinase Proteins 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- URIRWLJVWHYLET-ONGXEEELSA-N Val-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)C(C)C URIRWLJVWHYLET-ONGXEEELSA-N 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000011149 active material Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 3
- 108010077245 asparaginyl-proline Proteins 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 229940099500 cystamine Drugs 0.000 description 3
- 231100000409 cytocidal Toxicity 0.000 description 3
- 230000000445 cytocidal effect Effects 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 108010010096 glycyl-glycyl-tyrosine Proteins 0.000 description 3
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 231100000608 immunotoxin Toxicity 0.000 description 3
- 230000002637 immunotoxin Effects 0.000 description 3
- 229940051026 immunotoxin Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 101150066555 lacZ gene Proteins 0.000 description 3
- 108010064235 lysylglycine Proteins 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 235000009973 maize Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 3
- 239000003226 mitogen Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 108010018625 phenylalanylarginine Proteins 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical group 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 108020004418 ribosomal RNA Proteins 0.000 description 3
- 108010048818 seryl-histidine Proteins 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 238000013414 tumor xenograft model Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 2
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 2
- VHYRLCJMMJQUBY-UHFFFAOYSA-N 1-[4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCC1=CC=C(N2C(C=CC2=O)=O)C=C1 VHYRLCJMMJQUBY-UHFFFAOYSA-N 0.000 description 2
- IIRFMIKBXCMIPE-UHFFFAOYSA-N 2,5-dioxo-1-[6-[[2-[1-(pyridin-2-yldisulfanyl)ethyl]benzoyl]amino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound C=1C=CC=C(C(=O)NCCCCCC(=O)ON2C(C(CC2=O)S(O)(=O)=O)=O)C=1C(C)SSC1=CC=CC=N1 IIRFMIKBXCMIPE-UHFFFAOYSA-N 0.000 description 2
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 2
- 102100022987 Angiogenin Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000724256 Brome mosaic virus Species 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010013369 Enteropeptidase Proteins 0.000 description 2
- 102100029727 Enteropeptidase Human genes 0.000 description 2
- 241000672609 Escherichia coli BL21 Species 0.000 description 2
- 108050001049 Extracellular proteins Proteins 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- 101150015738 Fev gene Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Chemical group 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 102100031000 Hepatoma-derived growth factor Human genes 0.000 description 2
- 108091027305 Heteroduplex Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound 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 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- 108700005084 Multigene Family Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 101710182846 Polyhedrin Proteins 0.000 description 2
- CXGLFEOYCJFKPR-RCWTZXSCSA-N Pro-Thr-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O CXGLFEOYCJFKPR-RCWTZXSCSA-N 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 101500025337 Rattus norvegicus Heparin-binding EGF-like growth factor Proteins 0.000 description 2
- 241000219287 Saponaria Species 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 102100038803 Somatotropin Human genes 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 101100289792 Squirrel monkey polyomavirus large T gene Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 108010072788 angiogenin Proteins 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 108010049223 bryodin Proteins 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000008004 cell lysis buffer Substances 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 239000003145 cytotoxic factor Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012537 formulation buffer Substances 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 101150011498 lad gene Proteins 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 150000002669 lysines Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 238000007828 protein synthesis assay Methods 0.000 description 2
- 239000013014 purified material Substances 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- HHSGWIABCIVPJT-UHFFFAOYSA-M sodium;1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 HHSGWIABCIVPJT-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- YSGSDAIMSCVPHG-UHFFFAOYSA-N valyl-methionine Chemical compound CSCCC(C(O)=O)NC(=O)C(N)C(C)C YSGSDAIMSCVPHG-UHFFFAOYSA-N 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 238000012447 xenograft mouse model Methods 0.000 description 2
- HRANPRDGABOKNQ-ORGXEYTDSA-N (1r,3r,3as,3br,7ar,8as,8bs,8cs,10as)-1-acetyl-5-chloro-3-hydroxy-8b,10a-dimethyl-7-oxo-1,2,3,3a,3b,7,7a,8,8a,8b,8c,9,10,10a-tetradecahydrocyclopenta[a]cyclopropa[g]phenanthren-1-yl acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1[C@H](O)C[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 HRANPRDGABOKNQ-ORGXEYTDSA-N 0.000 description 1
- MPFUTQRKZCZACT-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(7-azido-4-methyl-2-oxochromen-3-yl)acetate Chemical compound N(=[N+]=[N-])C1=CC=C2C(=C(C(OC2=C1)=O)CC(=O)ON1C(CCC1=O)=O)C MPFUTQRKZCZACT-UHFFFAOYSA-N 0.000 description 1
- NKUZQMZWTZAPSN-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-bromoacetate Chemical compound BrCC(=O)ON1C(=O)CCC1=O NKUZQMZWTZAPSN-UHFFFAOYSA-N 0.000 description 1
- VQZYZXLBKBUOHE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)butanoate Chemical compound C=1C=CC=NC=1SSC(C)CC(=O)ON1C(=O)CCC1=O VQZYZXLBKBUOHE-UHFFFAOYSA-N 0.000 description 1
- VYEKJNGRMIAFMH-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(1-pyridin-2-ylsulfanylethyl)benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SC1=CC=CC=N1 VYEKJNGRMIAFMH-UHFFFAOYSA-N 0.000 description 1
- JSHOVKSMJRQOGY-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCSSC1=CC=CC=N1 JSHOVKSMJRQOGY-UHFFFAOYSA-N 0.000 description 1
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JBFQOLHAGBKPTP-NZATWWQASA-N (2s)-2-[[(2s)-4-carboxy-2-[[3-carboxy-2-[[(2s)-2,6-diaminohexanoyl]amino]propanoyl]amino]butanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)C(CC(O)=O)NC(=O)[C@@H](N)CCCCN JBFQOLHAGBKPTP-NZATWWQASA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 1
- WAOBCCBUTHNTFO-UHFFFAOYSA-N 2-(5-chloro-2-methyl-n-methylsulfonylanilino)-n-(2,6-difluorophenyl)acetamide Chemical compound CC1=CC=C(Cl)C=C1N(S(C)(=O)=O)CC(=O)NC1=C(F)C=CC=C1F WAOBCCBUTHNTFO-UHFFFAOYSA-N 0.000 description 1
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
- DQVAZKGVGKHQDS-UHFFFAOYSA-N 2-[[1-[2-[(2-amino-4-methylpentanoyl)amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoic acid Chemical compound CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(CC(C)C)C(O)=O DQVAZKGVGKHQDS-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 108020005096 28S Ribosomal RNA Proteins 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
- ABFYEILPZWAIBN-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.CN(C)CCCN=C=N ABFYEILPZWAIBN-UHFFFAOYSA-N 0.000 description 1
- JMUAKWNHKQBPGJ-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)-n-[4-[3-(pyridin-2-yldisulfanyl)propanoylamino]butyl]propanamide Chemical compound C=1C=CC=NC=1SSCCC(=O)NCCCCNC(=O)CCSSC1=CC=CC=N1 JMUAKWNHKQBPGJ-UHFFFAOYSA-N 0.000 description 1
- PCHRYHSDDPPZBV-UHFFFAOYSA-N 4-[[(5-chloro-2-methoxyanilino)-sulfanylidenemethyl]amino]-1-ethyl-3-pyrazolecarboxamide Chemical compound NC(=O)C1=NN(CC)C=C1NC(=S)NC1=CC(Cl)=CC=C1OC PCHRYHSDDPPZBV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- DBKNLHKEVPZVQC-LPEHRKFASA-N Arg-Ala-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O DBKNLHKEVPZVQC-LPEHRKFASA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 description 1
- 239000004475 Arginine Chemical group 0.000 description 1
- SDHFVYLZFBDSQT-DCAQKATOSA-N Asp-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N SDHFVYLZFBDSQT-DCAQKATOSA-N 0.000 description 1
- PAYPSKIBMDHZPI-CIUDSAMLSA-N Asp-Leu-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PAYPSKIBMDHZPI-CIUDSAMLSA-N 0.000 description 1
- WZUZGDANRQPCDD-SRVKXCTJSA-N Asp-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N WZUZGDANRQPCDD-SRVKXCTJSA-N 0.000 description 1
- BKOIIURTQAJHAT-GUBZILKMSA-N Asp-Pro-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 BKOIIURTQAJHAT-GUBZILKMSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000726103 Atta Species 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- 101100395863 Caenorhabditis elegans hst-2 gene Proteins 0.000 description 1
- 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 1
- 101100400999 Caenorhabditis elegans mel-28 gene Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 101710104316 Cell surface-binding protein Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- SBDVXRYCOIEYNV-YUMQZZPRSA-N Cys-His-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N SBDVXRYCOIEYNV-YUMQZZPRSA-N 0.000 description 1
- ABLJDBFJPUWQQB-DCAQKATOSA-N Cys-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N ABLJDBFJPUWQQB-DCAQKATOSA-N 0.000 description 1
- 101100239693 Dictyostelium discoideum myoD gene Proteins 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 101800000585 Diphtheria toxin fragment A Proteins 0.000 description 1
- 102000018386 EGF Family of Proteins Human genes 0.000 description 1
- 108010066486 EGF Family of Proteins Proteins 0.000 description 1
- 102000012545 EGF-like domains Human genes 0.000 description 1
- 108050002150 EGF-like domains Proteins 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 1
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 1
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 description 1
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 1
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 description 1
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 1
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- HPJLZFTUUJKWAJ-JHEQGTHGSA-N Glu-Gly-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O HPJLZFTUUJKWAJ-JHEQGTHGSA-N 0.000 description 1
- SWRVAQHFBRZVNX-GUBZILKMSA-N Glu-Lys-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SWRVAQHFBRZVNX-GUBZILKMSA-N 0.000 description 1
- HQRHFUYMGCHHJS-LURJTMIESA-N Gly-Gly-Arg Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N HQRHFUYMGCHHJS-LURJTMIESA-N 0.000 description 1
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- OOFLZRMKTMLSMH-UHFFFAOYSA-N H4atta Chemical compound OC(=O)CN(CC(O)=O)CC1=CC=CC(C=2N=C(C=C(C=2)C=2C3=CC=CC=C3C=C3C=CC=CC3=2)C=2N=C(CN(CC(O)=O)CC(O)=O)C=CC=2)=N1 OOFLZRMKTMLSMH-UHFFFAOYSA-N 0.000 description 1
- 101150101014 HST1 gene Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 102000018710 Heparin-binding EGF-like Growth Factor Human genes 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 1
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 1
- 101000716729 Homo sapiens Kit ligand Proteins 0.000 description 1
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
- 101150017040 I gene Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical group NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- APFJUBGRZGMQFF-QWRGUYRKSA-N Leu-Gly-Lys Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN APFJUBGRZGMQFF-QWRGUYRKSA-N 0.000 description 1
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 1
- DRWMRVFCKKXHCH-BZSNNMDCSA-N Leu-Phe-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CC=CC=C1 DRWMRVFCKKXHCH-BZSNNMDCSA-N 0.000 description 1
- PJWOOBTYQNNRBF-BZSNNMDCSA-N Leu-Phe-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)O)N PJWOOBTYQNNRBF-BZSNNMDCSA-N 0.000 description 1
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-N 0.000 description 1
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 1
- BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 1
- YSZNURNVYFUEHC-BQBZGAKWSA-N Lys-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(O)=O YSZNURNVYFUEHC-BQBZGAKWSA-N 0.000 description 1
- WINFHLHJTRGLCV-BZSNNMDCSA-N Lys-Tyr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=C(O)C=C1 WINFHLHJTRGLCV-BZSNNMDCSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- RPEPZINUYHUBKG-FXQIFTODSA-N Met-Cys-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O RPEPZINUYHUBKG-FXQIFTODSA-N 0.000 description 1
- HSJIGJRZYUADSS-IHRRRGAJSA-N Met-Lys-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HSJIGJRZYUADSS-IHRRRGAJSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100446506 Mus musculus Fgf3 gene Proteins 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 1
- 102000016349 Myosin Light Chains Human genes 0.000 description 1
- 108010067385 Myosin Light Chains Proteins 0.000 description 1
- 241001460678 Napo <wasp> Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000364057 Peoria Species 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- BNBBNGZZKQUWCD-IUCAKERBSA-N Pro-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H]1CCCN1 BNBBNGZZKQUWCD-IUCAKERBSA-N 0.000 description 1
- UIMCLYYSUCIUJM-UWVGGRQHSA-N Pro-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 UIMCLYYSUCIUJM-UWVGGRQHSA-N 0.000 description 1
- SXJOPONICMGFCR-DCAQKATOSA-N Pro-Ser-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O SXJOPONICMGFCR-DCAQKATOSA-N 0.000 description 1
- XNJVJEHDZPDPQL-BZSNNMDCSA-N Pro-Trp-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1)C(O)=O XNJVJEHDZPDPQL-BZSNNMDCSA-N 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 102100038358 Prostate-specific antigen Human genes 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 101710150344 Protein Rev Proteins 0.000 description 1
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 description 1
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101000704903 Saponaria officinalis Ribosome-inactivating protein saporin-6 Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- DKKGAAJTDKHWOD-BIIVOSGPSA-N Ser-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)N)C(=O)O DKKGAAJTDKHWOD-BIIVOSGPSA-N 0.000 description 1
- PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 1
- SGZVZUCRAVSPKQ-FXQIFTODSA-N Ser-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N SGZVZUCRAVSPKQ-FXQIFTODSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108090000054 Syndecan-2 Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000143014 T7virus Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- KBBRNEDOYWMIJP-KYNKHSRBSA-N Thr-Gly-Thr Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KBBRNEDOYWMIJP-KYNKHSRBSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- NMANTMWGQZASQN-QXEWZRGKSA-N Val-Arg-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N NMANTMWGQZASQN-QXEWZRGKSA-N 0.000 description 1
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 1
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- BTXLWRWDYZKCPQ-UHFFFAOYSA-N [nitro(phenyl)methyl] carbonochloridate Chemical compound ClC(=O)OC([N+](=O)[O-])C1=CC=CC=C1 BTXLWRWDYZKCPQ-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical group OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 108700040700 bacteriophage lambda cII Proteins 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000006364 cellular survival Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000005956 cytoplasmic translocation Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 108700021032 erbB Genes Proteins 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 101150045500 galK gene Proteins 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 108010073093 leucyl-glycyl-glycyl-glycine Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 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
- 230000001320 lysogenic effect Effects 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 108010089256 lysyl-aspartyl-glutamyl-leucine Proteins 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 239000009562 momordin Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- NFLNFBLCYHJLBN-UHFFFAOYSA-N n-[2-[2-(4-oxaldehydoylanilino)ethyldisulfanyl]ethyl]acetamide Chemical compound CC(=O)NCCSSCCNC1=CC=C(C(=O)C=O)C=C1 NFLNFBLCYHJLBN-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 230000001293 nucleolytic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 101150110245 ompC gene Proteins 0.000 description 1
- 101150073640 ompF gene Proteins 0.000 description 1
- 101150093139 ompT gene Proteins 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 229940070353 protamines Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000754 repressing effect Effects 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 102220058139 rs372082751 Human genes 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 108010060175 trypsinogen activation peptide Proteins 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000006648 viral gene expression Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/168—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
-
- 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
- A61K47/642—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 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
-
- 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
- A61K47/6425—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 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
- C07K14/503—Fibroblast growth factor [FGF] basic FGF [bFGF]
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/04—Fusion polypeptide containing a localisation/targetting motif containing an ER retention signal such as a C-terminal HDEL motif
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Botany (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US305771 | 1981-09-28 | ||
US441979 | 1982-11-15 | ||
US30577194A | 1994-09-13 | 1994-09-13 | |
US44197995A | 1995-05-16 | 1995-05-16 | |
PCT/US1995/012205 WO1996008274A2 (fr) | 1994-09-13 | 1995-09-13 | Conjugues d'un facteur de croissance semblable au facteur de croissance epidermique de type hbgf, et d'agents a cible definie |
Publications (1)
Publication Number | Publication Date |
---|---|
AU3724495A true AU3724495A (en) | 1996-03-29 |
Family
ID=26974775
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU37244/95A Abandoned AU3724495A (en) | 1994-09-13 | 1995-09-13 | Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU3724495A (fr) |
WO (1) | WO1996008274A2 (fr) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6037329A (en) | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
EP0833665A1 (fr) * | 1995-05-16 | 1998-04-08 | Prizm Pharmaceuticals, Inc. | Compositions contenant des acides nucleiques et des ligands pour un traitement therapeutique |
DE69629826T2 (de) | 1995-10-23 | 2004-07-01 | Children's Medical Center Corp., Boston | Therapeutische antiangiogenische zusammensetzungen und verfahren |
EP0923387B1 (fr) * | 1996-06-24 | 2001-09-26 | Selective Genetics, Inc. | Instruments medicaux recouverts d' heparine a usage intraveineux contenant des conjugues de facteur de croissance des fibroblastes |
US6838238B1 (en) | 1996-10-17 | 2005-01-04 | Invitrogen Corporation | Morphatides: novel shape and structure libraries |
CA2328774A1 (fr) * | 1998-04-17 | 1999-10-28 | John Warren | Procede servant a traiter la cystite interstitielle au moyen d'un facteur de croissance semblable au facteur de croissance epidermique de recombinaison se fixant a heparine (hb-egf) |
US7060433B1 (en) | 1999-11-12 | 2006-06-13 | Rigel Pharmaceuticals, Inc. | Methods and compositions for screening using diphtheria toxin constructs |
US7476726B1 (en) | 1999-09-14 | 2009-01-13 | The Children's Medical Center Corp. | Method of producing and purifying endostatin protein |
JP2003513670A (ja) * | 1999-11-12 | 2003-04-15 | ライジェル・ファーマシューティカルズ・インコーポレイテッド | ジフテリア毒素構築体を用いるスクリーニングのための方法および組成物 |
US8003595B2 (en) | 2000-03-01 | 2011-08-23 | Cellectis | Amino acid sequences facilitating penetration of a substance of interest into cells and/or cell nuclei |
FR2805821B1 (fr) * | 2000-03-01 | 2004-01-16 | Diatos | Sequences d'acides amines facilitant la penetration d'une substance d'interet a l'interieur des cellules et/ou des noyaux cellulaires |
WO2004096254A2 (fr) * | 2003-05-02 | 2004-11-11 | Xpression Antibody Therapeutics, Inc. | Compositions et procedes pour le traitement des tumeurs |
WO2004096117A2 (fr) * | 2003-05-02 | 2004-11-11 | Xpression Antibody Therapeutics, Inc. | Systemes d'administration d'acides nucleiques |
US8293700B2 (en) | 2003-08-14 | 2012-10-23 | Cellectis | Anti-bacterial composition especially for controlling gram-negative bacteria, comprising a peptide and an advantageously hydrophobic anti-bacterial agent |
WO2005033134A2 (fr) | 2003-09-30 | 2005-04-14 | Regeneron Pharmaceuticals, Inc. | Therapeutique et utilisations d'une proteine secretee |
GB0718045D0 (en) | 2007-09-14 | 2007-10-24 | Peptcell Ltd | Pharmaceutical compound |
PT2864360T (pt) * | 2012-06-25 | 2018-01-05 | The Brigham And Women`S Hospital Inc | Terapêuticas dirigidas ao alvo |
US9790264B2 (en) | 2012-06-25 | 2017-10-17 | The Brigham And Women's Hospital, Inc. | Compounds and methods for modulating pharmacokinetics |
WO2021261996A2 (fr) * | 2020-06-24 | 2021-12-30 | Sapreme Technologies B.V. | Conjugués de saponine à base de nhs |
CA3184041A1 (fr) * | 2020-06-24 | 2021-12-30 | Sapreme Technologies B.V. | Derives de saponine a fenetre therapeutique amelioree |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06502538A (ja) * | 1990-10-16 | 1994-03-24 | ザ チルドレンズメディカルセンターコーポレーション | 上皮細胞成長因子(egf)との相同性をもつヘパリン結合性マイトジェン |
US5916772A (en) * | 1992-06-16 | 1999-06-29 | Whittier Institute For Diabetes And Endocrinology | Recombinant production of saporin-containing proteins |
EP0712314A1 (fr) * | 1993-08-02 | 1996-05-22 | Prizm Pharmaceuticals, Inc. | Preparations monogenes de conjugues cytotoxiques |
WO1995024928A2 (fr) * | 1994-03-15 | 1995-09-21 | Prizm Pharmaceuticals, Inc. | Facteurs de croissance des fibroplastes pour la therapie genique et le traitement de troubles du segment anterieur de l'oeil |
-
1995
- 1995-09-13 AU AU37244/95A patent/AU3724495A/en not_active Abandoned
- 1995-09-13 WO PCT/US1995/012205 patent/WO1996008274A2/fr active Search and Examination
Also Published As
Publication number | Publication date |
---|---|
WO1996008274A2 (fr) | 1996-03-21 |
WO1996008274A3 (fr) | 1996-04-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6503886B1 (en) | Compositions containing nucleic acids and ligands for therapeutic treatment | |
WO1996006641A1 (fr) | Conjugues du facteur de croissance endothelial vasculaire avec des agents cibles | |
AU702323B2 (en) | Heparin-binding growth factors for gene therapy and anterior eye disorders | |
AU710309B2 (en) | Compositions containing nucleic acids and ligands for therapeutic treatment | |
AU3724495A (en) | Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents | |
CA2168647A1 (fr) | Preparations monogenes de conjugues cytotoxiques | |
US5962220A (en) | Compositions that specifically bind to colorectal cells and methods of using the same | |
EP1071717A1 (fr) | Molecules chimeres mutagenisees a base d'il-13 | |
US5916772A (en) | Recombinant production of saporin-containing proteins | |
US20030040496A1 (en) | Methods for halting unwanted cell growth, such as using ligand-directed nucleic acid delivery vehicles | |
EP0923387B1 (fr) | Instruments medicaux recouverts d' heparine a usage intraveineux contenant des conjugues de facteur de croissance des fibroblastes | |
Siegall et al. | Cytotoxic activity of chimeric proteins composed of acidic fibroblast growth factor and Pseudomonas exotoxin on a variety of cell types | |
WO1997049434A9 (fr) | Instruments medicaux heparines contenant des conjugues de facteur de croissance des fibroblastes | |
AU697469B2 (en) | Intracellular delivery of chemical agents to a specific cell type | |
US6803358B1 (en) | Ricin-like toxin variants for treatment of cancer, viral or parasitic infections | |
Gawlak et al. | Basic fibroblast growth factor-Pseudomonas exotoxin chimeric proteins; comparison with acidic fibroblast growth factor-Pseudomonas exotoxin | |
CA2342970A1 (fr) | Proteines de fusion |