AU2017322483A1 - Methods and compositions for treatment of lafora disease - Google Patents
Methods and compositions for treatment of lafora disease Download PDFInfo
- Publication number
- AU2017322483A1 AU2017322483A1 AU2017322483A AU2017322483A AU2017322483A1 AU 2017322483 A1 AU2017322483 A1 AU 2017322483A1 AU 2017322483 A AU2017322483 A AU 2017322483A AU 2017322483 A AU2017322483 A AU 2017322483A AU 2017322483 A1 AU2017322483 A1 AU 2017322483A1
- Authority
- AU
- Australia
- Prior art keywords
- chimeric polypeptide
- antibody
- amino acid
- seq
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 158
- 208000005870 Lafora disease Diseases 0.000 title claims abstract description 41
- 208000014161 Lafora myoclonic epilepsy Diseases 0.000 title claims abstract description 39
- 239000000203 mixture Substances 0.000 title abstract description 24
- 238000011282 treatment Methods 0.000 title description 15
- 239000012634 fragment Substances 0.000 claims description 475
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 475
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 463
- 229920001184 polypeptide Polymers 0.000 claims description 460
- 230000027455 binding Effects 0.000 claims description 363
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 331
- 239000000427 antigen Substances 0.000 claims description 318
- 108091007433 antigens Proteins 0.000 claims description 318
- 102000036639 antigens Human genes 0.000 claims description 318
- 210000004027 cell Anatomy 0.000 claims description 281
- 102000004139 alpha-Amylases Human genes 0.000 claims description 241
- 108090000637 alpha-Amylases Proteins 0.000 claims description 241
- 229940024171 alpha-amylase Drugs 0.000 claims description 241
- 241000282414 Homo sapiens Species 0.000 claims description 77
- 239000013598 vector Substances 0.000 claims description 58
- 150000001413 amino acids Chemical class 0.000 claims description 57
- 230000014509 gene expression Effects 0.000 claims description 48
- 230000000694 effects Effects 0.000 claims description 44
- 150000007523 nucleic acids Chemical class 0.000 claims description 39
- 102000039446 nucleic acids Human genes 0.000 claims description 37
- 108020004707 nucleic acids Proteins 0.000 claims description 37
- 108020001507 fusion proteins Proteins 0.000 claims description 29
- 102000037865 fusion proteins Human genes 0.000 claims description 29
- 210000000663 muscle cell Anatomy 0.000 claims description 27
- 210000002569 neuron Anatomy 0.000 claims description 25
- 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 claims description 23
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 23
- 210000004962 mammalian cell Anatomy 0.000 claims description 22
- 239000002773 nucleotide Substances 0.000 claims description 19
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- 210000004556 brain Anatomy 0.000 claims description 18
- 238000000338 in vitro Methods 0.000 claims description 18
- 230000013595 glycosylation Effects 0.000 claims description 15
- 238000006206 glycosylation reaction Methods 0.000 claims description 15
- 230000003301 hydrolyzing effect Effects 0.000 claims description 12
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 11
- 102000018428 Equilibrative nucleoside transporters Human genes 0.000 claims description 10
- 108050007554 Equilibrative nucleoside transporters Proteins 0.000 claims description 10
- 108010078791 Carrier Proteins Proteins 0.000 claims description 7
- 108020004705 Codon Proteins 0.000 claims description 7
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 7
- 241000238631 Hexapoda Species 0.000 claims description 6
- 210000005253 yeast cell Anatomy 0.000 claims description 6
- 210000004958 brain cell Anatomy 0.000 claims description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 5
- 241000271566 Aves Species 0.000 claims description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 2
- 210000004671 cell-free system Anatomy 0.000 claims description 2
- 102100021468 Equilibrative nucleoside transporter 2 Human genes 0.000 claims 1
- 101000822017 Homo sapiens Equilibrative nucleoside transporter 2 Proteins 0.000 claims 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 109
- 108020004414 DNA Proteins 0.000 description 98
- 108090000623 proteins and genes Proteins 0.000 description 97
- 235000001014 amino acid Nutrition 0.000 description 90
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 78
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 78
- 241001529936 Murinae Species 0.000 description 59
- 229940024606 amino acid Drugs 0.000 description 56
- 102000004169 proteins and genes Human genes 0.000 description 56
- 235000018102 proteins Nutrition 0.000 description 53
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 52
- 229920002527 Glycogen Polymers 0.000 description 52
- 229940096919 glycogen Drugs 0.000 description 52
- 238000006467 substitution reaction Methods 0.000 description 44
- 230000004071 biological effect Effects 0.000 description 42
- 108060003951 Immunoglobulin Proteins 0.000 description 41
- 230000000875 corresponding effect Effects 0.000 description 41
- 102000018358 immunoglobulin Human genes 0.000 description 41
- 239000003795 chemical substances by application Substances 0.000 description 34
- 230000004075 alteration Effects 0.000 description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
- 230000035508 accumulation Effects 0.000 description 30
- 238000009825 accumulation Methods 0.000 description 30
- 125000000539 amino acid group Chemical group 0.000 description 27
- 230000001976 improved effect Effects 0.000 description 27
- 201000010099 disease Diseases 0.000 description 26
- 230000001766 physiological effect Effects 0.000 description 25
- 210000004408 hybridoma Anatomy 0.000 description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 108010076504 Protein Sorting Signals Proteins 0.000 description 21
- 108091006544 SLC29A2 Proteins 0.000 description 20
- 210000000805 cytoplasm Anatomy 0.000 description 20
- 210000003205 muscle Anatomy 0.000 description 20
- 230000035515 penetration Effects 0.000 description 20
- 239000013604 expression vector Substances 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- 102000045002 Equilibrative nucleoside transporter 2 Human genes 0.000 description 18
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 18
- 238000003556 assay Methods 0.000 description 17
- 230000021615 conjugation Effects 0.000 description 17
- 208000007345 glycogen storage disease Diseases 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- 230000001413 cellular effect Effects 0.000 description 15
- 230000004927 fusion Effects 0.000 description 15
- 230000007423 decrease Effects 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 210000004185 liver Anatomy 0.000 description 14
- 239000012528 membrane Substances 0.000 description 14
- 210000004379 membrane Anatomy 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 14
- 239000013612 plasmid Substances 0.000 description 13
- 108091033319 polynucleotide Proteins 0.000 description 13
- 102000040430 polynucleotide Human genes 0.000 description 13
- 239000002157 polynucleotide Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 12
- 239000004382 Amylase Substances 0.000 description 12
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 12
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- 230000003247 decreasing effect Effects 0.000 description 12
- 210000000188 diaphragm Anatomy 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 11
- 229920001503 Glucan Polymers 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 229960001230 asparagine Drugs 0.000 description 11
- 235000009582 asparagine Nutrition 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 230000032258 transport Effects 0.000 description 11
- 239000004971 Cross linker Substances 0.000 description 10
- 230000004568 DNA-binding Effects 0.000 description 10
- 102000035195 Peptidases Human genes 0.000 description 10
- 108091005804 Peptidases Proteins 0.000 description 10
- 210000005229 liver cell Anatomy 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 230000029226 lipidation Effects 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 238000003380 quartz crystal microbalance Methods 0.000 description 9
- -1 triazene compound Chemical class 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 208000032008 Glycogen storage disease due to glycogen debranching enzyme deficiency Diseases 0.000 description 8
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 8
- 101000822041 Homo sapiens Equilibrative nucleoside transporter 3 Proteins 0.000 description 8
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 8
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 8
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 230000002776 aggregation Effects 0.000 description 8
- 238000004220 aggregation Methods 0.000 description 8
- 230000003172 anti-dna Effects 0.000 description 8
- 230000000975 bioactive effect Effects 0.000 description 8
- 230000001086 cytosolic effect Effects 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 239000012636 effector Substances 0.000 description 8
- 201000004543 glycogen storage disease III Diseases 0.000 description 8
- 230000002163 immunogen Effects 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 238000002823 phage display Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 230000033616 DNA repair Effects 0.000 description 7
- 102100022554 E3 ubiquitin-protein ligase NHLRC1 Human genes 0.000 description 7
- 102100035192 Laforin Human genes 0.000 description 7
- 230000004988 N-glycosylation Effects 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 239000003431 cross linking reagent Substances 0.000 description 7
- 230000006240 deamidation Effects 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 238000002703 mutagenesis Methods 0.000 description 7
- 231100000350 mutagenesis Toxicity 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 210000002027 skeletal muscle Anatomy 0.000 description 7
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 7
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 6
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 230000000747 cardiac effect Effects 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 201000004502 glycogen storage disease II Diseases 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 238000005304 joining Methods 0.000 description 6
- 210000003712 lysosome Anatomy 0.000 description 6
- 230000001868 lysosomic effect Effects 0.000 description 6
- 239000000816 peptidomimetic Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 101710197257 E3 ubiquitin-protein ligase NHLRC1 Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 102100021472 Equilibrative nucleoside transporter 3 Human genes 0.000 description 5
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 5
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- 101710192391 Laforin Proteins 0.000 description 5
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 208000025973 glycogen metabolism disease Diseases 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 210000004165 myocardium Anatomy 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 206010010904 Convulsion Diseases 0.000 description 4
- 150000008574 D-amino acids Chemical class 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-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
- 206010053250 Glycogen storage disease type III Diseases 0.000 description 4
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 4
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 208000002033 Myoclonus Diseases 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 230000004989 O-glycosylation Effects 0.000 description 4
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
- 102220545113 WD repeat-containing and planar cell polarity effector protein fritz homolog_T63S_mutation Human genes 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 108091092356 cellular DNA Proteins 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000001268 conjugating effect Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 230000004807 localization Effects 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 238000012510 peptide mapping method Methods 0.000 description 4
- 230000000737 periodic effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000004481 post-translational protein modification Effects 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 102220067473 rs199906203 Human genes 0.000 description 4
- 150000003384 small molecules Chemical group 0.000 description 4
- 238000007921 solubility assay Methods 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 241000024188 Andala Species 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000701822 Bovine papillomavirus Species 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 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 3
- 239000004472 Lysine Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000000149 penetrating effect Effects 0.000 description 3
- 150000003141 primary amines Chemical group 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 102200145330 rs72474224 Human genes 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 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 2
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 2
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 2
- NGXDNMNOQDVTRL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(4-azido-2-nitroanilino)hexanoate Chemical compound [O-][N+](=O)C1=CC(N=[N+]=[N-])=CC=C1NCCCCCC(=O)ON1C(=O)CCC1=O NGXDNMNOQDVTRL-UHFFFAOYSA-N 0.000 description 2
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 2
- AASYSXRGODIQGY-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)hexyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(CCCCC)N1C(=O)C=CC1=O AASYSXRGODIQGY-UHFFFAOYSA-N 0.000 description 2
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 101100433464 African swine fever virus (strain Badajoz 1971 Vero-adapted) BA71V-013 gene Proteins 0.000 description 2
- 102100033770 Alpha-amylase 1C Human genes 0.000 description 2
- 102000013142 Amylases Human genes 0.000 description 2
- 108010065511 Amylases Proteins 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102220571098 Chromodomain-helicase-DNA-binding protein 7_M37L_mutation Human genes 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 102220600635 DIS3-like exonuclease 1_Q46K_mutation Human genes 0.000 description 2
- 230000005778 DNA damage Effects 0.000 description 2
- 231100000277 DNA damage Toxicity 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010013643 Drop attacks Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102220590751 Epidermal growth factor receptor substrate 15_H80S_mutation Human genes 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000724791 Filamentous phage Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 206010053249 Glycogen Storage Disease Type IV Diseases 0.000 description 2
- 208000032003 Glycogen storage disease due to glucose-6-phosphatase deficiency Diseases 0.000 description 2
- 208000011123 Glycogen storage disease due to glycogen branching enzyme deficiency Diseases 0.000 description 2
- 206010018464 Glycogen storage disease type I Diseases 0.000 description 2
- 206010019075 Hallucination, visual Diseases 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 2
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 2
- 102220529338 Homer protein homolog 1_H38A_mutation Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000973111 Homo sapiens E3 ubiquitin-protein ligase NHLRC1 Proteins 0.000 description 2
- 101000876418 Homo sapiens Laforin Proteins 0.000 description 2
- 101000882389 Homo sapiens Laforin, isoform 9 Proteins 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 108010029785 Pancreatic alpha-Amylases Proteins 0.000 description 2
- 102100026367 Pancreatic alpha-amylase Human genes 0.000 description 2
- 102220531697 Pleckstrin homology domain-containing family A member 8_R18L_mutation Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102220542835 Presenilins-associated rhomboid-like protein, mitochondrial_E84P_mutation Human genes 0.000 description 2
- 101000959719 Rattus norvegicus AP-3 complex subunit mu-1 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- 108010026386 Salivary alpha-Amylases Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 235000019418 amylase Nutrition 0.000 description 2
- 230000003556 anti-epileptic effect Effects 0.000 description 2
- 238000003452 antibody preparation method Methods 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 230000002886 autophagic effect Effects 0.000 description 2
- 210000004957 autophagosome Anatomy 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 102220377136 c.10C>A Human genes 0.000 description 2
- 102220481134 cAMP-dependent protein kinase catalytic subunit beta_K13Q_mutation Human genes 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002742 combinatorial mutagenesis Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 201000004541 glycogen storage disease I Diseases 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000009830 intercalation Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 102200089625 rs104893829 Human genes 0.000 description 2
- 102220224707 rs1060500984 Human genes 0.000 description 2
- 102200010092 rs1060505039 Human genes 0.000 description 2
- 102220235788 rs1131691637 Human genes 0.000 description 2
- 102200001997 rs121908107 Human genes 0.000 description 2
- 102220243686 rs1555618729 Human genes 0.000 description 2
- 102220049920 rs201523857 Human genes 0.000 description 2
- 102200044494 rs28903098 Human genes 0.000 description 2
- 102220123277 rs372312214 Human genes 0.000 description 2
- 102200105532 rs397509387 Human genes 0.000 description 2
- 102200089582 rs5030804 Human genes 0.000 description 2
- 102220082637 rs61743884 Human genes 0.000 description 2
- 102200058106 rs63749967 Human genes 0.000 description 2
- 102200145327 rs72561723 Human genes 0.000 description 2
- 102220112074 rs72766563 Human genes 0.000 description 2
- 102220121358 rs770065197 Human genes 0.000 description 2
- 102220270128 rs781438362 Human genes 0.000 description 2
- 102200087321 rs864309648 Human genes 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000002784 stomach Anatomy 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
- 206010042772 syncope Diseases 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003573 thiols Chemical group 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 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 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 102220587867 Acidic mammalian chitinase_S22T_mutation Human genes 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000713842 Avian sarcoma virus Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 229940126161 DNA alkylating agent Drugs 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000002266 Dual-Specificity Phosphatases Human genes 0.000 description 1
- 108010000518 Dual-Specificity Phosphatases Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 102100021469 Equilibrative nucleoside transporter 1 Human genes 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
- 102000042092 Glucose transporter family Human genes 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 101000822020 Homo sapiens Equilibrative nucleoside transporter 1 Proteins 0.000 description 1
- 101000713320 Homo sapiens Equilibrative nucleoside transporter 4 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102220470856 Interferon-induced helicase C domain-containing protein 1_S88A_mutation Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- ZOKXTWBITQBERF-AKLPVKDBSA-N Molybdenum Mo-99 Chemical compound [99Mo] ZOKXTWBITQBERF-AKLPVKDBSA-N 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 241001315609 Pittosporum crassifolium Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102100036407 Thioredoxin Human genes 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 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
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 230000037037 animal physiology Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 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
- 125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006743 cytoplasmic accumulation Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- LRPQMNYCTSPGCX-UHFFFAOYSA-N dimethyl pimelimidate Chemical compound COC(=N)CCCCCC(=N)OC LRPQMNYCTSPGCX-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 231100000025 genetic toxicology Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 150000004676 glycans Polymers 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000001456 gonadotroph Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000027086 plasmid maintenance Effects 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 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 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 1
- 102200082904 rs33974228 Human genes 0.000 description 1
- 102200006407 rs746834149 Human genes 0.000 description 1
- 108010038196 saccharide-binding proteins Proteins 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000010741 sumoylation Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002849 thermal shift Methods 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
- C12N9/2411—Amylases
- C12N9/2414—Alpha-amylase (3.2.1.1.)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662385656P | 2016-09-09 | 2016-09-09 | |
| US62/385,656 | 2016-09-09 | ||
| US201762553048P | 2017-08-31 | 2017-08-31 | |
| US62/553,048 | 2017-08-31 | ||
| PCT/US2017/050787 WO2018049237A1 (en) | 2016-09-09 | 2017-09-08 | Methods and compositions for treatment of lafora disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2017322483A1 true AU2017322483A1 (en) | 2019-04-04 |
Family
ID=61562328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017322483A Abandoned AU2017322483A1 (en) | 2016-09-09 | 2017-09-08 | Methods and compositions for treatment of lafora disease |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US10781433B2 (enExample) |
| EP (1) | EP3509614A4 (enExample) |
| JP (1) | JP2019535645A (enExample) |
| CN (1) | CN109963576A (enExample) |
| AU (1) | AU2017322483A1 (enExample) |
| CA (1) | CA3036524A1 (enExample) |
| WO (1) | WO2018049237A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6178785B2 (ja) | 2011-04-01 | 2017-08-09 | イェール ユニバーシティーYale University | 細胞浸透性抗dna抗体およびdna修復を阻害するためのその使用 |
| WO2017218824A1 (en) | 2016-06-15 | 2017-12-21 | Yale University | Anti-guanosine antibody as a molecular delivery vehicle |
| US11590242B2 (en) | 2016-06-15 | 2023-02-28 | Yale University | Antibody-mediated autocatalytic, targeted delivery of nanocarriers to tumors |
| KR20220049568A (ko) * | 2019-08-22 | 2022-04-21 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 엔젤만 증후군의 치료를 위한 ube3a |
| KR102814185B1 (ko) | 2023-07-20 | 2025-06-12 | 제닉스큐어 주식회사 | 라포라병을 예방 또는 치료하기 위한 재조합 아데노 연관 바이러스 및 이를 포함하는 약학적 조성물 |
| WO2025018822A1 (ko) | 2023-07-20 | 2025-01-23 | 제닉스큐어 주식회사 | 라포라병을 예방 또는 치료하기 위한 재조합 아데노 연관 바이러스 및 이를 포함하는 약학적 조성물 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI1011236A2 (pt) * | 2009-06-15 | 2019-07-09 | 4S3 Bioscience Inc | métodos e composições para tratamento de miopatia miotubular usando polipeptídeos quiméricos compreendendo polipeptídeos miotubularesih 1 (mtm1) |
| US20130273026A1 (en) | 2012-04-12 | 2013-10-17 | Integrative Enzymatics, Inc. | Composition and method for modulating inflammatory molecules with amylase |
| CN105189543A (zh) * | 2013-02-20 | 2015-12-23 | 瓦莱里昂治疗有限责任公司 | 治疗福布斯科里病的方法和组合物 |
| CA2901978A1 (en) * | 2013-02-20 | 2014-08-28 | Valerion Therapeutics, Llc | Methods and compositions for treatment of pompe disease |
| EP3711820A1 (en) * | 2014-01-13 | 2020-09-23 | Valerion Therapeutics, LLC | Internalizing moieties |
| CA2989294A1 (en) * | 2014-06-13 | 2015-12-17 | Valerion Therapeutics, Llc | Methods and compositions for treatment of glycogen storage diseases and glycogen metabolism disorders |
| CA2995673A1 (en) * | 2014-08-27 | 2016-03-03 | Valerion Therapeutics, Llc | Internalizing moieties for treatment of cancer |
-
2017
- 2017-09-08 CA CA3036524A patent/CA3036524A1/en not_active Abandoned
- 2017-09-08 US US16/332,331 patent/US10781433B2/en active Active
- 2017-09-08 JP JP2019513898A patent/JP2019535645A/ja active Pending
- 2017-09-08 CN CN201780069052.6A patent/CN109963576A/zh active Pending
- 2017-09-08 EP EP17849664.2A patent/EP3509614A4/en not_active Withdrawn
- 2017-09-08 WO PCT/US2017/050787 patent/WO2018049237A1/en not_active Ceased
- 2017-09-08 AU AU2017322483A patent/AU2017322483A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA3036524A1 (en) | 2018-03-15 |
| JP2019535645A (ja) | 2019-12-12 |
| WO2018049237A1 (en) | 2018-03-15 |
| EP3509614A4 (en) | 2020-04-22 |
| CN109963576A (zh) | 2019-07-02 |
| US20190316104A1 (en) | 2019-10-17 |
| EP3509614A1 (en) | 2019-07-17 |
| US10781433B2 (en) | 2020-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10703824B2 (en) | Internalizing moieties | |
| US10781433B2 (en) | Methods and compositions for treatment of Lafora disease | |
| US20210040464A1 (en) | Methods and compositions for treatment of polyglucosan disorders | |
| US10781434B2 (en) | Methods and compositions for treatment of glycogen storage diseases and glycogen metabolism disorders | |
| US20180028676A1 (en) | Methods and compositions for treatment of forbes-cori disease | |
| CN103379915A (zh) | Hsa相关组合物及使用方法 | |
| KR20130020765A (ko) | Hsa-관련 조성물 및 사용방법 | |
| AU2014218854A1 (en) | Methods and compositions for treatment of Pompe disease | |
| WO2013177428A1 (en) | Methods for increasing muscle contractility | |
| US20210395716A1 (en) | Methods and compositions for treatment of protein aggregation-based disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |