EP0571554A1 - Grundstruktur immunogener polypeptide mit epitopen für hcv, antikörper, polynukleotidsequenzen, impfstoffe und verfahren - Google Patents
Grundstruktur immunogener polypeptide mit epitopen für hcv, antikörper, polynukleotidsequenzen, impfstoffe und verfahrenInfo
- Publication number
- EP0571554A1 EP0571554A1 EP92907699A EP92907699A EP0571554A1 EP 0571554 A1 EP0571554 A1 EP 0571554A1 EP 92907699 A EP92907699 A EP 92907699A EP 92907699 A EP92907699 A EP 92907699A EP 0571554 A1 EP0571554 A1 EP 0571554A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- recited
- hcv
- polypeptide
- antibody
- basic
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 666
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 530
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 527
- 230000002163 immunogen Effects 0.000 title claims abstract description 158
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 102
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 102
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 102
- 238000000034 method Methods 0.000 title claims abstract description 64
- 229960005486 vaccine Drugs 0.000 title claims description 42
- 239000000523 sample Substances 0.000 claims abstract description 84
- 238000003018 immunoassay Methods 0.000 claims abstract description 46
- 238000003556 assay Methods 0.000 claims abstract description 40
- 230000003302 anti-idiotype Effects 0.000 claims abstract description 17
- 238000003259 recombinant expression Methods 0.000 claims abstract description 16
- 150000001413 amino acids Chemical class 0.000 claims description 188
- 239000012634 fragment Substances 0.000 claims description 96
- 239000000427 antigen Substances 0.000 claims description 90
- 108091007433 antigens Proteins 0.000 claims description 89
- 102000036639 antigens Human genes 0.000 claims description 89
- 108020004414 DNA Proteins 0.000 claims description 76
- 125000000539 amino acid group Chemical group 0.000 claims description 60
- 230000000692 anti-sense effect Effects 0.000 claims description 55
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 34
- 239000002773 nucleotide Substances 0.000 claims description 30
- 125000003729 nucleotide group Chemical group 0.000 claims description 30
- 238000002372 labelling Methods 0.000 claims description 26
- 208000015181 infectious disease Diseases 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 239000013612 plasmid Substances 0.000 claims description 21
- 230000000295 complement effect Effects 0.000 claims description 20
- 239000002671 adjuvant Substances 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 17
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 16
- 208000027761 Hepatic autoimmune disease Diseases 0.000 claims description 15
- 108091081024 Start codon Proteins 0.000 claims description 15
- 210000000582 semen Anatomy 0.000 claims description 15
- 239000004475 Arginine Substances 0.000 claims description 13
- 108091026890 Coding region Proteins 0.000 claims description 13
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 230000014509 gene expression Effects 0.000 claims description 11
- 239000004472 Lysine Substances 0.000 claims description 10
- 241000700618 Vaccinia virus Species 0.000 claims description 9
- 108010076039 Polyproteins Proteins 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 102000053602 DNA Human genes 0.000 claims description 7
- 230000003053 immunization Effects 0.000 claims description 6
- 238000011534 incubation Methods 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000010836 blood and blood product Substances 0.000 claims description 5
- 108700026244 Open Reading Frames Proteins 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 10
- 229940125691 blood product Drugs 0.000 claims 3
- 241000711549 Hepacivirus C Species 0.000 abstract description 369
- 210000002966 serum Anatomy 0.000 abstract description 48
- 108090000623 proteins and genes Proteins 0.000 abstract description 33
- 102000004169 proteins and genes Human genes 0.000 abstract description 19
- 238000001514 detection method Methods 0.000 abstract description 17
- 241001227713 Chiron Species 0.000 abstract description 8
- 238000003119 immunoblot Methods 0.000 abstract description 6
- 238000006386 neutralization reaction Methods 0.000 abstract description 6
- 208000002672 hepatitis B Diseases 0.000 abstract description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 abstract description 4
- 238000002965 ELISA Methods 0.000 abstract description 3
- 230000002068 genetic effect Effects 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 230000003321 amplification Effects 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 208000005252 hepatitis A Diseases 0.000 abstract 1
- 238000003199 nucleic acid amplification method Methods 0.000 abstract 1
- 238000005215 recombination Methods 0.000 abstract 1
- 230000006798 recombination Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 159
- 229940024606 amino acid Drugs 0.000 description 159
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 49
- 210000004027 cell Anatomy 0.000 description 47
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 45
- 241000700605 Viruses Species 0.000 description 44
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 37
- 210000004369 blood Anatomy 0.000 description 36
- 239000008280 blood Substances 0.000 description 36
- 102000039446 nucleic acids Human genes 0.000 description 36
- 108020004707 nucleic acids Proteins 0.000 description 36
- 150000007523 nucleic acids Chemical class 0.000 description 36
- KAKIEONGVIRLLB-UHFFFAOYSA-N CBOC Chemical compound CBOC KAKIEONGVIRLLB-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- 238000012360 testing method Methods 0.000 description 32
- 239000013598 vector Substances 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 27
- 208000006454 hepatitis Diseases 0.000 description 26
- OVVUNXXROOFSIM-SDDRHHMPSA-N Arg-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O OVVUNXXROOFSIM-SDDRHHMPSA-N 0.000 description 25
- 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 25
- 239000002953 phosphate buffered saline Substances 0.000 description 25
- 231100000283 hepatitis Toxicity 0.000 description 24
- QYRMBFWDSFGSFC-OLHMAJIHSA-N Asn-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QYRMBFWDSFGSFC-OLHMAJIHSA-N 0.000 description 23
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 21
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 20
- 235000018417 cysteine Nutrition 0.000 description 19
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 19
- 101100315624 Caenorhabditis elegans tyr-1 gene Proteins 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 241000700721 Hepatitis B virus Species 0.000 description 17
- TZJSEJOXAIWOST-RHYQMDGZSA-N Thr-Lys-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N TZJSEJOXAIWOST-RHYQMDGZSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 108010068380 arginylarginine Proteins 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- JFOKLAPFYCTNHW-SRVKXCTJSA-N Gln-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N JFOKLAPFYCTNHW-SRVKXCTJSA-N 0.000 description 14
- 238000002835 absorbance Methods 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 14
- 229920000136 polysorbate Polymers 0.000 description 14
- -1 tyrosine amino acid Chemical class 0.000 description 14
- XMVZMBGFIOQONW-GARJFASQSA-N Cys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)C(=O)O XMVZMBGFIOQONW-GARJFASQSA-N 0.000 description 13
- IRKWVRSEQFTGGV-VEVYYDQMSA-N Thr-Asn-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IRKWVRSEQFTGGV-VEVYYDQMSA-N 0.000 description 13
- 230000001154 acute effect Effects 0.000 description 13
- DNBMCNQKNOKOSD-DCAQKATOSA-N Arg-Pro-Gln Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O DNBMCNQKNOKOSD-DCAQKATOSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 101100068676 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gln-1 gene Proteins 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 12
- 229960000723 ampicillin Drugs 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 206010019799 Hepatitis viral Diseases 0.000 description 10
- YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 10
- 108010062796 arginyllysine Proteins 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- 238000003127 radioimmunoassay Methods 0.000 description 10
- 201000001862 viral hepatitis Diseases 0.000 description 10
- 229910001868 water Inorganic materials 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 9
- SVSQSPICRKBMSZ-SRVKXCTJSA-N Lys-Pro-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O SVSQSPICRKBMSZ-SRVKXCTJSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 239000008363 phosphate buffer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000010561 standard procedure Methods 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 8
- ZTKHZAXGTFXUDD-VEVYYDQMSA-N Arg-Asn-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZTKHZAXGTFXUDD-VEVYYDQMSA-N 0.000 description 8
- RIQBRKVTFBWEDY-RHYQMDGZSA-N Arg-Lys-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RIQBRKVTFBWEDY-RHYQMDGZSA-N 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 8
- 241000709721 Hepatovirus A Species 0.000 description 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 8
- DBMLDOWSVHMQQN-XGEHTFHBSA-N Met-Ser-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DBMLDOWSVHMQQN-XGEHTFHBSA-N 0.000 description 8
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 7
- IXFVOPOHSRKJNG-LAEOZQHASA-N Gln-Asp-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O IXFVOPOHSRKJNG-LAEOZQHASA-N 0.000 description 7
- ALSRJRIWBNENFY-DCAQKATOSA-N Lys-Arg-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O ALSRJRIWBNENFY-DCAQKATOSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 230000001580 bacterial 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
- 230000001553 hepatotropic effect Effects 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 210000004408 hybridoma Anatomy 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 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 6
- GMRGSBAMMMVDGG-GUBZILKMSA-N Asn-Arg-Arg Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N GMRGSBAMMMVDGG-GUBZILKMSA-N 0.000 description 6
- NLCZGISONIGRQP-DCAQKATOSA-N Cys-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N NLCZGISONIGRQP-DCAQKATOSA-N 0.000 description 6
- 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 6
- 241000724675 Hepatitis E virus Species 0.000 description 6
- 208000037262 Hepatitis delta Diseases 0.000 description 6
- 241000724709 Hepatitis delta virus Species 0.000 description 6
- NLZVTPYXYXMCIP-XUXIUFHCSA-N Ile-Pro-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O NLZVTPYXYXMCIP-XUXIUFHCSA-N 0.000 description 6
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 239000011543 agarose gel Substances 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000012472 biological sample Substances 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000001962 electrophoresis Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 5
- 206010003445 Ascites Diseases 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- GDNWBSFSHJVXKL-GUBZILKMSA-N Cys-Lys-Gln Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O GDNWBSFSHJVXKL-GUBZILKMSA-N 0.000 description 5
- 238000009007 Diagnostic Kit Methods 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 108010065920 Insulin Lispro Proteins 0.000 description 5
- LSIWVWRUTKPXDS-DCAQKATOSA-N Pro-Gln-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LSIWVWRUTKPXDS-DCAQKATOSA-N 0.000 description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000010166 immunofluorescence Methods 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-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
- 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 4
- WTZUSCUIVPVCRH-SRVKXCTJSA-N Lys-Gln-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WTZUSCUIVPVCRH-SRVKXCTJSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 108020005038 Terminator Codon Proteins 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 239000012620 biological material Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
- LEVWYRKDKASIDU-IMJSIDKUSA-N cystine group Chemical group C([C@@H](C(=O)O)N)SSC[C@@H](C(=O)O)N LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 210000005229 liver cell Anatomy 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 238000003260 vortexing Methods 0.000 description 4
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108090000565 Capsid Proteins Proteins 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 102100023321 Ceruloplasmin Human genes 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 206010023126 Jaundice Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 241000283977 Oryctolagus Species 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- NRCJWSGXMAPYQX-LPEHRKFASA-N Ser-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CO)N)C(=O)O NRCJWSGXMAPYQX-LPEHRKFASA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 108010093581 aspartyl-proline Proteins 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- KHWCHTKSEGGWEX-UHFFFAOYSA-N deoxyadenylic acid Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(O)=O)O1 KHWCHTKSEGGWEX-UHFFFAOYSA-N 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000002550 fecal effect Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 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 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 239000013600 plasmid vector Substances 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 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 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- LTFMZDNNPPEQNG-KVQBGUIXSA-N 2'-deoxyguanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 LTFMZDNNPPEQNG-KVQBGUIXSA-N 0.000 description 2
- 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 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- UISQLSIBJKEJSS-GUBZILKMSA-N Arg-Arg-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(O)=O UISQLSIBJKEJSS-GUBZILKMSA-N 0.000 description 2
- GRRXPUAICOGISM-RWMBFGLXSA-N Arg-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GRRXPUAICOGISM-RWMBFGLXSA-N 0.000 description 2
- VENMDXUVHSKEIN-GUBZILKMSA-N Arg-Ser-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VENMDXUVHSKEIN-GUBZILKMSA-N 0.000 description 2
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 2
- ALHMNHZJBYBYHS-DCAQKATOSA-N Asn-Lys-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ALHMNHZJBYBYHS-DCAQKATOSA-N 0.000 description 2
- ZKAOJVJQGVUIIU-GUBZILKMSA-N Asp-Pro-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZKAOJVJQGVUIIU-GUBZILKMSA-N 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 102100021277 Beta-secretase 2 Human genes 0.000 description 2
- 101710150190 Beta-secretase 2 Proteins 0.000 description 2
- 101100392772 Caenorhabditis elegans gln-2 gene Proteins 0.000 description 2
- 101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 description 2
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 108010009685 Cholinergic Receptors Proteins 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- BCFXQBXXDSEHRS-FXQIFTODSA-N Cys-Ser-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BCFXQBXXDSEHRS-FXQIFTODSA-N 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- JRHPEMVLTRADLJ-AVGNSLFASA-N Gln-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JRHPEMVLTRADLJ-AVGNSLFASA-N 0.000 description 2
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 2
- 206010019791 Hepatitis post transfusion Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- 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 2
- FUKDBQGFSJUXGX-RWMBFGLXSA-N Lys-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N)C(=O)O FUKDBQGFSJUXGX-RWMBFGLXSA-N 0.000 description 2
- RIJCHEVHFWMDKD-SRVKXCTJSA-N Lys-Lys-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RIJCHEVHFWMDKD-SRVKXCTJSA-N 0.000 description 2
- PLDJDCJLRCYPJB-VOAKCMCISA-N Lys-Lys-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PLDJDCJLRCYPJB-VOAKCMCISA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- LNLNHXIQPGKRJQ-SRVKXCTJSA-N Pro-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1 LNLNHXIQPGKRJQ-SRVKXCTJSA-N 0.000 description 2
- KTFZQPLSPLWLKN-KKUMJFAQSA-N Pro-Gln-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KTFZQPLSPLWLKN-KKUMJFAQSA-N 0.000 description 2
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 2
- XSXABUHLKPUVLX-JYJNAYRXSA-N Pro-Ser-Trp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O XSXABUHLKPUVLX-JYJNAYRXSA-N 0.000 description 2
- QUBVFEANYYWBTM-VEVYYDQMSA-N Pro-Thr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O QUBVFEANYYWBTM-VEVYYDQMSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 239000003391 RNA probe Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- NNFMANHDYSVNIO-DCAQKATOSA-N Ser-Lys-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NNFMANHDYSVNIO-DCAQKATOSA-N 0.000 description 2
- BCAVNDNYOGTQMQ-AAEUAGOBSA-N Ser-Trp-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(O)=O BCAVNDNYOGTQMQ-AAEUAGOBSA-N 0.000 description 2
- 206010042566 Superinfection Diseases 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- 101150006914 TRP1 gene Proteins 0.000 description 2
- XYEXCEPTALHNEV-RCWTZXSCSA-N Thr-Arg-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XYEXCEPTALHNEV-RCWTZXSCSA-N 0.000 description 2
- MGJLBZFUXUGMML-VOAKCMCISA-N Thr-Lys-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MGJLBZFUXUGMML-VOAKCMCISA-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
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 102000034337 acetylcholine receptors Human genes 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- NWMHDZMRVUOQGL-CZEIJOLGSA-N almurtide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)CO[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O NWMHDZMRVUOQGL-CZEIJOLGSA-N 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 230000004596 appetite loss Effects 0.000 description 2
- 108010060035 arginylproline Proteins 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 2
- 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 2
- 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 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- LTFMZDNNPPEQNG-UHFFFAOYSA-N deoxyguanylic acid Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(COP(O)(O)=O)O1 LTFMZDNNPPEQNG-UHFFFAOYSA-N 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000521 hyperimmunizing effect Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000012917 library technology Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 208000019017 loss of appetite Diseases 0.000 description 2
- 235000021266 loss of appetite Nutrition 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 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
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000005582 sexual transmission Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
- 108010038745 tryptophylglycine Proteins 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- 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 1
- QMXCRMQIVATQMR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-pyridin-2-ylsulfanylpropanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSC1=CC=CC=N1 QMXCRMQIVATQMR-UHFFFAOYSA-N 0.000 description 1
- CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- XRMDCWJNPDVAFI-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-ol Chemical compound CC1(C)CC(O)CC(C)(C)[N+]1=O XRMDCWJNPDVAFI-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- LQILVUYCDHSGEU-UHFFFAOYSA-N 4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1CN1C(=O)C=CC1=O LQILVUYCDHSGEU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- XDRAUWJCGKIAGX-YXZULKJRSA-N 6-bromo-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1Br XDRAUWJCGKIAGX-YXZULKJRSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010059193 Acute hepatitis B Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- MTANSHNQTWPZKP-KKUMJFAQSA-N Arg-Gln-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)O MTANSHNQTWPZKP-KKUMJFAQSA-N 0.000 description 1
- SSZGOKWBHLOCHK-DCAQKATOSA-N Arg-Lys-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N SSZGOKWBHLOCHK-DCAQKATOSA-N 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- REQUGIWGOGSOEZ-ZLUOBGJFSA-N Asn-Ser-Asn Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)C(=O)N REQUGIWGOGSOEZ-ZLUOBGJFSA-N 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 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
- 241000588832 Bordetella pertussis Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100033620 Calponin-1 Human genes 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- UKVGHFORADMBEN-GUBZILKMSA-N Cys-Arg-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UKVGHFORADMBEN-GUBZILKMSA-N 0.000 description 1
- QLCPDGRAEJSYQM-LPEHRKFASA-N Cys-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N)C(=O)O QLCPDGRAEJSYQM-LPEHRKFASA-N 0.000 description 1
- KGIHMGPYGXBYJJ-SRVKXCTJSA-N Cys-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CS KGIHMGPYGXBYJJ-SRVKXCTJSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 241000701832 Enterobacteria phage T3 Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000701047 Gallid alphaherpesvirus 2 Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- KWUSGAIFNHQCBY-DCAQKATOSA-N Gln-Arg-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O KWUSGAIFNHQCBY-DCAQKATOSA-N 0.000 description 1
- 208000032982 Hemorrhagic Fever with Renal Syndrome Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 1
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-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
- VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 description 1
- 241001298245 Lauria Species 0.000 description 1
- QQUJSUFWEDZQQY-AVGNSLFASA-N Lys-Gln-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN QQUJSUFWEDZQQY-AVGNSLFASA-N 0.000 description 1
- CUHGAUZONORRIC-HJGDQZAQSA-N Lys-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N)O CUHGAUZONORRIC-HJGDQZAQSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- WEDDFMCSUNNZJR-WDSKDSINSA-N Met-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(O)=O WEDDFMCSUNNZJR-WDSKDSINSA-N 0.000 description 1
- 101710202709 Middle T antigen Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108700015872 N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine Proteins 0.000 description 1
- 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 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
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000053208 Porcellio laevis Species 0.000 description 1
- PZSCUPVOJGKHEP-CIUDSAMLSA-N Pro-Gln-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O PZSCUPVOJGKHEP-CIUDSAMLSA-N 0.000 description 1
- 208000037048 Prodromal Symptoms Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 108020004518 RNA Probes Proteins 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101710132906 Structural polyprotein Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 239000008049 TAE buffer Substances 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 241000473945 Theria <moth genus> Species 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 101900209501 Vaccinia virus Thymidine kinase Proteins 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- FVSAHFFHPOLBLL-SHYZEUOFSA-N [(2r,3s,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate Chemical group O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)C1 FVSAHFFHPOLBLL-SHYZEUOFSA-N 0.000 description 1
- 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 1
- 229960000583 acetic acid Drugs 0.000 description 1
- HGEVZDLYZYVYHD-UHFFFAOYSA-N acetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound CC(O)=O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O HGEVZDLYZYVYHD-UHFFFAOYSA-N 0.000 description 1
- 208000037628 acute hepatitis B virus infection Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000000211 autoradiogram Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 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
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 210000004520 cell wall skeleton Anatomy 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000006642 detritylation reaction Methods 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002635 electroconvulsive therapy Methods 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003623 enhancer Substances 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
- 230000007717 exclusion Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012530 fluid Substances 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
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000012817 gel-diffusion technique Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 101150106093 gpt gene Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 230000000423 heterosexual effect Effects 0.000 description 1
- 230000000652 homosexual effect Effects 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- XMBWDFGMSWQBCA-RNFDNDRNSA-M iodine-131(1-) Chemical compound [131I-] XMBWDFGMSWQBCA-RNFDNDRNSA-M 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 108700007621 mifamurtide Proteins 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000009612 semen analysis Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000012154 short term therapy Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- XETCRXVKJHBPMK-MJSODCSWSA-N trehalose 6,6'-dimycolate Chemical compound C([C@@H]1[C@H]([C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](COC(=O)C(CCCCCCCCCCC3C(C3)CCCCCCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)O2)O)O1)O)OC(=O)C(C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC XETCRXVKJHBPMK-MJSODCSWSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 208000016254 weariness Diseases 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- 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
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1081—Togaviridae, e.g. flavivirus, rubella virus, hog cholera virus
- C07K16/109—Hepatitis C virus; Hepatitis G virus
-
- 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
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US63980991A | 1991-01-14 | 1991-01-14 | |
US639809 | 1991-01-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0571554A1 true EP0571554A1 (de) | 1993-12-01 |
Family
ID=24565635
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP92907699A Withdrawn EP0571554A1 (de) | 1991-01-14 | 1992-01-14 | Grundstruktur immunogener polypeptide mit epitopen für hcv, antikörper, polynukleotidsequenzen, impfstoffe und verfahren |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0571554A1 (de) |
AU (1) | AU1459792A (de) |
WO (1) | WO1992012992A2 (de) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9105871D0 (en) * | 1991-03-20 | 1991-05-08 | Inst Cientifico Tecnol Navarra | Synthetic peptides |
DE4209215A1 (de) * | 1991-07-04 | 1993-01-07 | Boehringer Mannheim Gmbh | Hcv peptidantigene und verfahren zur bestimmung von hcv |
CA2120340A1 (en) * | 1991-10-02 | 1994-04-15 | Kaichiro Ishibashi | Reagents for testing for hepatitis c and method of testing for the same |
DE4240980A1 (de) * | 1992-08-07 | 1994-02-10 | Boehringer Mannheim Gmbh | HCV Peptidantigene und Verfahren zur Bestimmung von HCV |
JPH06311885A (ja) * | 1992-08-25 | 1994-11-08 | Mitsubishi Kasei Corp | C型肝炎ウイルス遺伝子に相補的なアンチセンス化合物 |
US6174868B1 (en) * | 1992-09-10 | 2001-01-16 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of hepatitis C virus-associated diseases |
WO1994005813A1 (en) * | 1992-09-10 | 1994-03-17 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Compositions and methods for treatment of hepatitis c virus-associated diseases |
JPH10503364A (ja) * | 1994-05-10 | 1998-03-31 | ザ ジェネラル ホスピタル コーポレーション | C型肝炎ウイルスのアンチセンス阻害 |
AU707811B2 (en) * | 1995-05-05 | 1999-07-22 | Australian Water Technologies Pty Ltd | Method for the detection of viable Cryptosporidium parvum oocysts |
AUPN283195A0 (en) * | 1995-05-05 | 1995-06-01 | Australian Water Technologies Pty Ltd | Method for the detection of viable cryptosporidium parvum cells |
IT1285158B1 (it) * | 1996-09-17 | 1998-06-03 | Angeletti P Ist Richerche Bio | Polipeptidi solubili con l'attivita' di serino-proteasi di ns3 del virus dell'epatite c, e procedimento per la loro preparazione e il |
AU4497999A (en) * | 1998-04-28 | 1999-11-16 | Ingrid-Corina Bergter | Radioimmunopharmaca for treating hepatitis c |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GEP20002164B (en) * | 1989-05-18 | 2000-07-10 | Novartis Vaccines & Diagnostic | Oligomers, method for detecting of hcv sequence, kit for its detecting, method for production of the blood free from hcv |
CA2032907C (en) * | 1989-12-22 | 2002-05-14 | Richard R. Lesniewski | Hepatitis c assay |
KR940000755B1 (ko) * | 1990-02-16 | 1994-01-29 | 유나이티드 바이오메디칼 인코오포레이티드 | Hcv에 대한 항체 검출, hcv 감염의 진단 및 백신으로서의 그 예방에 특히 적합한 합성 펩티드 |
ZA912040B (en) * | 1990-03-30 | 1991-12-24 | Akzo Nv | Peptides immunochemically reactive with antibodies directed against hepatitis non-a,non-b virus |
EP0543924B1 (de) * | 1990-08-10 | 1997-06-18 | Chiron Corporation | Nanbv diagnostik: für die untersuchung auf hepatitis c verwendbare polynukleotide |
JP3114731B2 (ja) * | 1990-08-14 | 2000-12-04 | 国立感染症研究所長 | C型肝炎ウイルス抗体検出用ペプチド抗原及びその使用方法 |
EP0479376B1 (de) * | 1990-10-05 | 1995-01-25 | Akzo Nobel N.V. | Mit Antikörper gegen Hepatitis-Virus non-A, non-B immunochemisch reagierende Peptide |
EP0485209A1 (de) * | 1990-11-08 | 1992-05-13 | Immuno Japan Inc. | Mit Non-A Non-B Hepatitis Virus verwandtes Antigen, Aufspürsysteme für Antikörper, Polynukleotide und Polypeptide |
DE69030124T2 (de) * | 1990-12-14 | 1997-09-18 | Innogenetics Nv | Synthetische Antigene zum Nachweis von Antikörpern gegen Hepatitis C-Virus |
-
1992
- 1992-01-14 EP EP92907699A patent/EP0571554A1/de not_active Withdrawn
- 1992-01-14 WO PCT/US1992/000356 patent/WO1992012992A2/en not_active Application Discontinuation
- 1992-01-14 AU AU14597/92A patent/AU1459792A/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO9212992A2 * |
Also Published As
Publication number | Publication date |
---|---|
AU1459792A (en) | 1992-08-27 |
WO1992012992A2 (en) | 1992-08-06 |
WO1992012992A3 (en) | 1993-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2065287C (en) | New hcv isolates | |
Zibert et al. | Epitope mapping of antibodies directed against hypervariable region 1 in acute self-limiting and chronic infections due to hepatitis C virus | |
JP4296174B2 (ja) | G型肝炎ウイルスおよびその分子クローニング | |
RU2148587C1 (ru) | Полипептид и способ его получения, реагент для иммуноанализа, способ определения присутствия антител и способ индукции иммунного ответа | |
US5856437A (en) | Hepatitis C virus isolate polypeptides | |
US6071693A (en) | HCV genomic sequences for diagnostics and therapeutics | |
RU2155228C2 (ru) | Hcv геномные последовательности для диагностических и терапевтических целей | |
Scarselli et al. | Occurrence of antibodies reactive with more than one variant of the putative envelope glycoprotein (gp70) hypervariable region 1 in viremic hepatitis C virus-infected patients | |
US6210962B1 (en) | Nucleotide and peptide sequences of an isolate of the hepatitis C virus, diagnostic and therapeutic applications thereof | |
US7557199B2 (en) | Hepatitis C virus vaccine | |
US5766840A (en) | Hepatitis G virus and molecular cloning thereof | |
EP0623169B1 (de) | Impfstoff gegen den hepatitis e-virus und verfahren | |
US5885768A (en) | Hepatitis E virus peptide antigen and antibodies | |
EP0571554A1 (de) | Grundstruktur immunogener polypeptide mit epitopen für hcv, antikörper, polynukleotidsequenzen, impfstoffe und verfahren | |
WO1994018217A1 (en) | Non-a, non-b, non-c, non-d, non-e hepatitis reagents and methods for their use | |
US5741490A (en) | Hepatitis E virus vaccine and method | |
US7252827B1 (en) | Conserved motif of hepatitis C virus E2/NS1 region | |
WO1995032290A2 (en) | Non-a/non-b/non-c/non-d/non-e hepatitis agents and molecular cloning thereof | |
US5859230A (en) | Non-A/non-B/non-C/non-D/non-E hepatitis agents and molecular cloning thereof | |
US5874563A (en) | Hepatitis G virus and molecular cloning thereof | |
JPH11500001A (ja) | E型肝炎のパキスタン菌株の組み換えタンパク質並びにその診断法及び種痘における利用 | |
US5866139A (en) | Nucleotide and peptide sequences of a hepatitis C virus isolate, diagnostic and therapeutic applications | |
AU684177C (en) | Hepatitis G virus and molecular cloning thereof | |
EP1536013A1 (de) | Zur hepatitisdiagnose geeignete dna-sequenz und dadurch codiertes polypeptid | |
LV10306B (en) | Nanbv diagnostics and vaccines |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU MC NL SE |
|
17P | Request for examination filed |
Effective date: 19930813 |
|
17Q | First examination report despatched |
Effective date: 19960620 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19961031 |