JP5686468B2 - Ｂ型肝炎ウイルス（ＨＢＶ）の疎水性修飾されたｐｒｅＳ由来ペプチド及び肝臓に化合物を特異的に送達するためのビヒクルとしてのそれらの使用 - Google Patents
Ｂ型肝炎ウイルス（ＨＢＶ）の疎水性修飾されたｐｒｅＳ由来ペプチド及び肝臓に化合物を特異的に送達するためのビヒクルとしてのそれらの使用 Download PDFInfo
- Publication number
- JP5686468B2 JP5686468B2 JP2010543441A JP2010543441A JP5686468B2 JP 5686468 B2 JP5686468 B2 JP 5686468B2 JP 2010543441 A JP2010543441 A JP 2010543441A JP 2010543441 A JP2010543441 A JP 2010543441A JP 5686468 B2 JP5686468 B2 JP 5686468B2
- Authority
- JP
- Japan
- Prior art keywords
- liver
- hbv
- pres
- compound
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 241000700721 Hepatitis B virus Species 0.000 title claims description 175
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 147
- 210000004185 liver Anatomy 0.000 title claims description 108
- 150000001875 compounds Chemical class 0.000 title claims description 76
- 102000004196 processed proteins & peptides Human genes 0.000 title description 58
- 210000003494 hepatocyte Anatomy 0.000 claims description 53
- 239000003814 drug Substances 0.000 claims description 45
- 208000019423 liver disease Diseases 0.000 claims description 45
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 42
- 229940079593 drug Drugs 0.000 claims description 38
- 208000015181 infectious disease Diseases 0.000 claims description 37
- 108090000623 proteins and genes Proteins 0.000 claims description 30
- 102000004169 proteins and genes Human genes 0.000 claims description 27
- 230000002265 prevention Effects 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 21
- 241000700605 Viruses Species 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 18
- 238000003745 diagnosis Methods 0.000 claims description 14
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 13
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 13
- 230000010933 acylation Effects 0.000 claims description 12
- 238000005917 acylation reaction Methods 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 208000006454 hepatitis Diseases 0.000 claims description 12
- 231100000283 hepatitis Toxicity 0.000 claims description 12
- 201000004792 malaria Diseases 0.000 claims description 12
- 201000004409 schistosomiasis Diseases 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 208000037262 Hepatitis delta Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 208000002672 hepatitis B Diseases 0.000 claims description 9
- 208000029570 hepatitis D virus infection Diseases 0.000 claims description 9
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 125000006850 spacer group Chemical group 0.000 claims description 7
- 238000007920 subcutaneous administration Methods 0.000 claims description 7
- 208000005331 Hepatitis D Diseases 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 6
- 239000002872 contrast media Substances 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000002163 immunogen Effects 0.000 claims description 6
- 208000014018 liver neoplasm Diseases 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 230000037396 body weight Effects 0.000 claims description 5
- 230000028993 immune response Effects 0.000 claims description 5
- 229940079322 interferon Drugs 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229960005486 vaccine Drugs 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 4
- 208000018565 Hemochromatosis Diseases 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 230000030741 antigen processing and presentation Effects 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 239000007850 fluorescent dye Substances 0.000 claims description 4
- 239000002502 liposome Substances 0.000 claims description 4
- 230000003908 liver function Effects 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 4
- 244000052613 viral pathogen Species 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 208000004554 Leishmaniasis Diseases 0.000 claims description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 3
- 108020004459 Small interfering RNA Proteins 0.000 claims description 3
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 3
- 230000009918 complex formation Effects 0.000 claims description 3
- 238000002591 computed tomography Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 208000037972 tropical disease Diseases 0.000 claims description 3
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims description 2
- 102000018832 Cytochromes Human genes 0.000 claims description 2
- 108010052832 Cytochromes Proteins 0.000 claims description 2
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 2
- 206010019695 Hepatic neoplasm Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 230000033228 biological regulation Effects 0.000 claims description 2
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical group [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 claims description 2
- 229960005179 primaquine Drugs 0.000 claims description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 150000007970 thio esters Chemical class 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 102000007698 Alcohol dehydrogenase Human genes 0.000 claims 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 claims 2
- 229940043355 kinase inhibitor Drugs 0.000 claims 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 2
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 claims 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 206010019663 Hepatic failure Diseases 0.000 claims 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 claims 1
- 229940079156 Proteasome inhibitor Drugs 0.000 claims 1
- 229940122423 Viral RNA polymerase inhibitor Drugs 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 230000000593 degrading effect Effects 0.000 claims 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 230000006126 farnesylation Effects 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 231100000835 liver failure Toxicity 0.000 claims 1
- 208000007903 liver failure Diseases 0.000 claims 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
- 239000003207 proteasome inhibitor Substances 0.000 claims 1
- 102000009929 raf Kinases Human genes 0.000 claims 1
- 108010077182 raf Kinases Proteins 0.000 claims 1
- 101150115433 SLC26A5 gene Proteins 0.000 description 155
- 125000000539 amino acid group Chemical group 0.000 description 57
- 235000001014 amino acid Nutrition 0.000 description 55
- 210000004027 cell Anatomy 0.000 description 41
- 229940024606 amino acid Drugs 0.000 description 40
- 150000001413 amino acids Chemical class 0.000 description 39
- 230000002209 hydrophobic effect Effects 0.000 description 34
- 230000004048 modification Effects 0.000 description 29
- 238000012986 modification Methods 0.000 description 29
- 235000018102 proteins Nutrition 0.000 description 23
- 230000008685 targeting Effects 0.000 description 21
- 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 19
- 238000006467 substitution reaction Methods 0.000 description 19
- 108091035707 Consensus sequence Proteins 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 14
- 244000045947 parasite Species 0.000 description 13
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
- 238000009825 accumulation Methods 0.000 description 11
- 210000004899 c-terminal region Anatomy 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 230000002440 hepatic effect Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 210000005229 liver cell Anatomy 0.000 description 10
- 108010091867 peptide P Proteins 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 241000285424 HBV genotype C Species 0.000 description 9
- 241000724709 Hepatitis delta virus Species 0.000 description 9
- 241000282414 Homo sapiens Species 0.000 description 9
- 108010028921 Lipopeptides Proteins 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000013459 approach Methods 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 150000007523 nucleic acids Chemical class 0.000 description 7
- -1 polycyclic aromatic compounds Chemical class 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 description 6
- 101710085938 Matrix protein Proteins 0.000 description 6
- 101710127721 Membrane protein Proteins 0.000 description 6
- 102100032965 Myomesin-2 Human genes 0.000 description 6
- 230000005847 immunogenicity Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000011191 terminal modification Methods 0.000 description 6
- 241000701447 unidentified baculovirus Species 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 241000282693 Cercopithecidae Species 0.000 description 5
- 102100031673 Corneodesmosin Human genes 0.000 description 5
- 102220600635 DIS3-like exonuclease 1_Q46K_mutation Human genes 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 108010052285 Membrane Proteins Proteins 0.000 description 5
- 102000018697 Membrane Proteins Human genes 0.000 description 5
- 238000011785 NMRI mouse Methods 0.000 description 5
- 241000223960 Plasmodium falciparum Species 0.000 description 5
- 229940096437 Protein S Drugs 0.000 description 5
- 108010031318 Vitronectin Proteins 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 238000010166 immunofluorescence Methods 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 4
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 4
- 101100505076 Caenorhabditis elegans gly-2 gene Proteins 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 208000021642 Muscular disease Diseases 0.000 description 4
- 201000009623 Myopathy Diseases 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 210000000013 bile duct Anatomy 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 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 4
- 208000016361 genetic disease Diseases 0.000 description 4
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 4
- 230000003494 hepatotrophic effect Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 150000008574 D-amino acids Chemical class 0.000 description 3
- 125000003301 D-leucyl group Chemical group N[C@@H](C(=O)*)CC(C)C 0.000 description 3
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical group OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 3
- 229920002527 Glycogen Polymers 0.000 description 3
- 102100034349 Integrase Human genes 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 3
- 101100170937 Mus musculus Dnmt1 gene Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011210 chromatographic step Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 229940096919 glycogen Drugs 0.000 description 3
- 231100000234 hepatic damage Toxicity 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 230000008818 liver damage Effects 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 108700029353 mouse Ifna Proteins 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000007498 myristoylation Effects 0.000 description 3
- 230000003071 parasitic effect Effects 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 2
- 201000011374 Alagille syndrome Diseases 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
- 208000007257 Budd-Chiari syndrome Diseases 0.000 description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
- 206010010317 Congenital absence of bile ducts Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000255925 Diptera Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 208000009139 Gilbert Disease Diseases 0.000 description 2
- 208000022412 Gilbert syndrome Diseases 0.000 description 2
- 241000285387 HBV genotype A Species 0.000 description 2
- 241000285452 HBV genotype B Species 0.000 description 2
- 241000285366 HBV genotype D Species 0.000 description 2
- 241000285370 HBV genotype E Species 0.000 description 2
- 241000285563 HBV genotype F Species 0.000 description 2
- 241000285576 HBV genotype G Species 0.000 description 2
- 241000285579 HBV genotype H Species 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 2
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 2
- 208000028782 Hereditary disease Diseases 0.000 description 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241000282675 Lagothrix Species 0.000 description 2
- 101710192606 Latent membrane protein 2 Proteins 0.000 description 2
- 208000024556 Mendelian disease Diseases 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 241000224016 Plasmodium Species 0.000 description 2
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
- 201000002150 Progressive familial intrahepatic cholestasis Diseases 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 241000242678 Schistosoma Species 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 101710109576 Terminal protein Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 208000018839 Wilson disease Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 201000007930 alcohol dependence Diseases 0.000 description 2
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 201000005271 biliary atresia Diseases 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001784 detoxification Methods 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 108010042430 galactose receptor Proteins 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 208000007345 glycogen storage disease Diseases 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 210000002989 hepatic vein Anatomy 0.000 description 2
- 231100000334 hepatotoxic Toxicity 0.000 description 2
- 230000003082 hepatotoxic effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- VWQWXZAWFPZJDA-CGVGKPPMSA-N hydrocortisone succinate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC(O)=O)[C@@H]4[C@@H]3CCC2=C1 VWQWXZAWFPZJDA-CGVGKPPMSA-N 0.000 description 2
- 229950006240 hydrocortisone succinate Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- 108091005601 modified peptides Proteins 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 2
- 108010011110 polyarginine Proteins 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 102200006618 rs727503094 Human genes 0.000 description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 201000001862 viral hepatitis Diseases 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Chemical class 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 241000256186 Anopheles <genus> Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000002476 Falciparum Malaria Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108010016306 Glycylpeptide N-tetradecanoyltransferase Proteins 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010078049 Interferon alpha-2 Proteins 0.000 description 1
- 102100039350 Interferon alpha-7 Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical class CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241000255134 Lutzomyia <genus> Species 0.000 description 1
- 102000034452 Methionyl aminopeptidases Human genes 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 208000010359 Newcastle Disease Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 101800005149 Peptide B Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 241000722350 Phlebotomus <genus> Species 0.000 description 1
- 206010035500 Plasmodium falciparum infection Diseases 0.000 description 1
- 201000011336 Plasmodium falciparum malaria Diseases 0.000 description 1
- 241000223801 Plasmodium knowlesi Species 0.000 description 1
- 241000223821 Plasmodium malariae Species 0.000 description 1
- 241001505293 Plasmodium ovale Species 0.000 description 1
- 241000223810 Plasmodium vivax Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000242683 Schistosoma haematobium Species 0.000 description 1
- 241000242687 Schistosoma intercalatum Species 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 241001520868 Schistosoma mekongi Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108010032099 V(D)J recombination activating protein 2 Proteins 0.000 description 1
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229940118555 Viral entry inhibitor Drugs 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960001997 adefovir Drugs 0.000 description 1
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- JPIYZTWMUGTEHX-UHFFFAOYSA-N auramine O free base Chemical compound C1=CC(N(C)C)=CC=C1C(=N)C1=CC=C(N(C)C)C=C1 JPIYZTWMUGTEHX-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000005831 deiodination reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000214 effect on organisms Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229940099052 fuzeon Drugs 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000005161 hepatic lobe Anatomy 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000011488 interferon-alpha production Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 229940040511 liver extract Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000003936 merozoite Anatomy 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- DUAFKXOFBZQTQE-IXZVNPRYSA-N myristoyl-coa Chemical compound O[C@@H]1[C@@H](OP(O)(O)=O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OCC(C)(C)[C@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 DUAFKXOFBZQTQE-IXZVNPRYSA-N 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229920005615 natural polymer Chemical class 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000008385 outer phase Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229940118768 plasmodium malariae Drugs 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003307 reticuloendothelial effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000013097 stability assessment Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229920001059 synthetic polymer Chemical class 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010863 targeted diagnosis Methods 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport 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
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/033—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the internal surface of the plasma membrane, e.g. containing a myristoylation motif
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
- C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
- C12N2810/6036—DNA rev transcr viruses
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6234708P | 2008-01-25 | 2008-01-25 | |
| US61/062,347 | 2008-01-25 | ||
| PCT/EP2009/000477 WO2009092612A1 (en) | 2008-01-25 | 2009-01-26 | Hydrophobic modified pres-derived peptides of hepatitis b virus (hbv) and their use as vehicles for the specific delivery of compounds to the liver |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011512123A JP2011512123A (ja) | 2011-04-21 |
| JP2011512123A5 JP2011512123A5 (enExample) | 2012-03-08 |
| JP5686468B2 true JP5686468B2 (ja) | 2015-03-18 |
Family
ID=40521848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010543441A Expired - Fee Related JP5686468B2 (ja) | 2008-01-25 | 2009-01-26 | Ｂ型肝炎ウイルス（ＨＢＶ）の疎水性修飾されたｐｒｅＳ由来ペプチド及び肝臓に化合物を特異的に送達するためのビヒクルとしてのそれらの使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9868768B2 (enExample) |
| EP (1) | EP2245047B1 (enExample) |
| JP (1) | JP5686468B2 (enExample) |
| CN (1) | CN102015753A (enExample) |
| ES (1) | ES2847288T3 (enExample) |
| WO (1) | WO2009092612A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9755242B2 (en) | 2008-05-21 | 2017-09-05 | Wirtz Manufacturing Co., Inc. | Reformed battery grids |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1281761A1 (en) | 2001-07-27 | 2003-02-05 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Hepatitis B virus pre-S1 derived synthetic polypeptides and their use thereof. |
| EP2117576B1 (en) | 2007-02-08 | 2014-04-16 | University Of Utah Research Foundation | Methods and compositions related to inhibition of viral entry |
| SG178254A1 (en) * | 2009-08-07 | 2012-03-29 | Transgene Sa | Composition for treating hbv infection |
| CN102241744B (zh) * | 2010-05-14 | 2015-03-04 | 上海贺普药业股份有限公司 | 一种病毒感染阻断剂、其药物组合物及其应用 |
| WO2012106403A2 (en) * | 2011-02-01 | 2012-08-09 | Uab Research Foundation | Methods and compositions for pseudoinfectious alphaviruses |
| CN103402545B (zh) * | 2011-02-10 | 2017-04-05 | 海德堡鲁普雷希特卡尔斯大学 | 疏水性经修饰肽及其在肝特异性靶向中的用途 |
| US10363323B2 (en) | 2011-02-10 | 2019-07-30 | Ruprecht-Karls-Universitat Heidelberg | Hydrophobic modified peptides for liver specific diagnosis |
| EP2691105B1 (en) | 2011-03-28 | 2018-07-11 | University of Utah Research Foundation | Methods and compositions related to inhibition of viral entry |
| CN109354623B (zh) * | 2012-04-25 | 2022-06-24 | 华辉安健（北京）生物科技有限公司 | 乙肝肝炎病毒功能性受体的组成以及相关应用 |
| EP2703001A1 (en) | 2012-08-26 | 2014-03-05 | XAX Kft. | Tumor vaccination |
| CN103665095A (zh) * | 2012-09-11 | 2014-03-26 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | 一种疏水性多肽修饰抗体的合成方法 |
| US8961995B2 (en) * | 2012-09-20 | 2015-02-24 | Uab Research Foundation | Methods and compositions for alphavirus replicons |
| EP2917231B1 (en) | 2012-11-12 | 2019-03-06 | Ruprecht-Karls-Universität Heidelberg | Lipopeptides for use in treating liver diseases and cardiovascular diseases |
| ES2922883T3 (es) * | 2014-10-07 | 2022-09-21 | Myr Gmbh | Tratamiento combinado de la infección por VHB y VHD |
| EP3138579A1 (en) * | 2015-09-05 | 2017-03-08 | Biomay Ag | Fusion protein for use in the treatment of a hepatitis b virus infection |
| EP3189850A1 (en) * | 2015-12-16 | 2017-07-12 | Ruprecht-Karls-Universität Heidelberg | Liver targeting of cyclic pres-derived peptides of hbv |
| EP3181146A1 (en) | 2015-12-16 | 2017-06-21 | Ruprecht-Karls-Universität Heidelberg | Cyclic ntcp-targeting peptides and their uses as entry inhibitors |
| CN109069577B (zh) | 2016-01-07 | 2022-08-19 | 纳维根公司 | Hiv进入的d-肽抑制剂以及使用方法 |
| WO2018054891A1 (en) | 2016-09-20 | 2018-03-29 | Ruprecht-Karls-Universität | Compounds and combinations thereof for preventing and/or treating hbv and/or hdv infections |
| EP3392267A1 (en) * | 2017-04-18 | 2018-10-24 | Myr GmbH | Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitors |
| CN109718364A (zh) * | 2017-10-27 | 2019-05-07 | 上海贺普药业股份有限公司 | 充分剂量条件下治疗乙肝病毒相关肝病的药物和方法 |
| US11497808B2 (en) | 2019-09-30 | 2022-11-15 | Gilead Sciences, Inc. | HBV vaccines and methods treating HBV |
| EP3804750A1 (en) | 2019-10-10 | 2021-04-14 | Universität Heidelberg | Conjugate compounds for preventing and/or treating hbv and/or hdv infections, liver diseases and for targeting ntcp |
| WO2021168575A1 (en) * | 2020-02-27 | 2021-09-02 | Quadrumix Biotechnology Inc. | Polypeptides directed against viral infection and uses thereof |
| JP2024535127A (ja) | 2021-09-14 | 2024-09-26 | アドファファーム ゲーエムベーハー | 新規リポペプチド製剤 |
| WO2025031397A1 (zh) * | 2023-08-08 | 2025-02-13 | 前沿生物药业(南京)股份有限公司 | 钠离子-牛磺胆酸共转运蛋白长效抑制剂及其应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5204096A (en) * | 1984-03-07 | 1993-04-20 | New York Blood Center, Inc. | Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers |
| EP1281761A1 (en) * | 2001-07-27 | 2003-02-05 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Hepatitis B virus pre-S1 derived synthetic polypeptides and their use thereof. |
| CN101045156B (zh) | 2006-03-29 | 2012-05-02 | 刘宏利 | 特异靶向性药物及其用途 |
| WO2008103380A2 (en) * | 2007-02-21 | 2008-08-28 | Fox Chase Cancer Center | Hepatitis b virus compositions and methods of use |
-
2009
- 2009-01-26 JP JP2010543441A patent/JP5686468B2/ja not_active Expired - Fee Related
- 2009-01-26 ES ES09704030T patent/ES2847288T3/es active Active
- 2009-01-26 WO PCT/EP2009/000477 patent/WO2009092612A1/en not_active Ceased
- 2009-01-26 EP EP09704030.7A patent/EP2245047B1/en not_active Not-in-force
- 2009-01-26 US US12/864,197 patent/US9868768B2/en active Active
- 2009-01-26 CN CN2009801125069A patent/CN102015753A/zh active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9755242B2 (en) | 2008-05-21 | 2017-09-05 | Wirtz Manufacturing Co., Inc. | Reformed battery grids |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2245047A1 (en) | 2010-11-03 |
| ES2847288T3 (es) | 2021-08-02 |
| US20110027183A1 (en) | 2011-02-03 |
| WO2009092612A1 (en) | 2009-07-30 |
| EP2245047B1 (en) | 2020-11-18 |
| JP2011512123A (ja) | 2011-04-21 |
| CN102015753A (zh) | 2011-04-13 |
| US9868768B2 (en) | 2018-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5686468B2 (ja) | Ｂ型肝炎ウイルス（ＨＢＶ）の疎水性修飾されたｐｒｅＳ由来ペプチド及び肝臓に化合物を特異的に送達するためのビヒクルとしてのそれらの使用 | |
| AU2009207806B2 (en) | Hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) and their use as HBV and HBV entry inhibitors | |
| EP2673004B1 (en) | Hydrophobic modified peptides and their use for liver specific targeting | |
| JP2017081952A (ja) | 肝臓特異的診断のための疎水性修飾ペプチド | |
| EP3189850A1 (en) | Liver targeting of cyclic pres-derived peptides of hbv | |
| HK1150168B (en) | Hydrophobic modified pres-derived peptides of hepatitis b virus (hbv) and their use as hbv and hdv entry inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120119 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120119 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130219 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131107 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140131 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140715 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141111 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20141209 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150114 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150119 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5686468 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |