CA2441378A1 - Nucleic acid molecules encoding serine protease cvsp14, the encoded polypeptides and methods based thereon - Google Patents

Info

Publication number

CA2441378A1

CA2441378A1 CA002441378A CA2441378A CA2441378A1 CA 2441378 A1 CA2441378 A1 CA 2441378A1 CA 002441378 A CA002441378 A CA 002441378A CA 2441378 A CA2441378 A CA 2441378A CA 2441378 A1 CA2441378 A1 CA 2441378A1

Authority

CA

Canada

Prior art keywords

polypeptide

cvsp14

sequence

nucleotides

nucleic acid

Prior art date

2001-03-22

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

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 464
• 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 401
• 229920001184 polypeptide Polymers 0.000 title claims abstract description 348
• 150000007523 nucleic acids Chemical class 0.000 title claims description 192
• 102000039446 nucleic acids Human genes 0.000 title claims description 186
• 108020004707 nucleic acids Proteins 0.000 title claims description 186
• 238000000034 method Methods 0.000 title claims description 183
• 102000012479 Serine Proteases Human genes 0.000 title description 71
• 108010022999 Serine Proteases Proteins 0.000 title description 71
• 108091005804 Peptidases Proteins 0.000 claims abstract description 253
• 239000004365 Protease Substances 0.000 claims abstract description 253
• 150000001875 compounds Chemical class 0.000 claims abstract description 174
• 230000000694 effects Effects 0.000 claims abstract description 145
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 90
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 25
• 108090000623 proteins and genes Proteins 0.000 claims description 283
• 210000004027 cell Anatomy 0.000 claims description 170
• 125000003729 nucleotide group Chemical group 0.000 claims description 120
• 239000002773 nucleotide Substances 0.000 claims description 115
• 235000001014 amino acid Nutrition 0.000 claims description 108
• 150000001413 amino acids Chemical class 0.000 claims description 95
• 239000003795 chemical substances by application Substances 0.000 claims description 83
• 238000012360 testing method Methods 0.000 claims description 82
• 239000012634 fragment Substances 0.000 claims description 65
• 230000027455 binding Effects 0.000 claims description 57
• 239000000758 substrate Substances 0.000 claims description 56
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
• 239000013598 vector Substances 0.000 claims description 51
• 239000000523 sample Substances 0.000 claims description 43
• 239000000126 substance Substances 0.000 claims description 43
• 210000001519 tissue Anatomy 0.000 claims description 40
• 241000282414 Homo sapiens Species 0.000 claims description 38
• 201000010099 disease Diseases 0.000 claims description 37
• 230000003197 catalytic effect Effects 0.000 claims description 36
• 241001465754 Metazoa Species 0.000 claims description 33
• 102000010911 Enzyme Precursors Human genes 0.000 claims description 31
• 108010062466 Enzyme Precursors Proteins 0.000 claims description 31
• 239000003112 inhibitor Substances 0.000 claims description 31
• 201000011510 cancer Diseases 0.000 claims description 29
• 230000004913 activation Effects 0.000 claims description 28
• 238000006467 substitution reaction Methods 0.000 claims description 27
• 230000002797 proteolythic effect Effects 0.000 claims description 25
• 230000000295 complement effect Effects 0.000 claims description 24
• 230000001225 therapeutic effect Effects 0.000 claims description 24
• 230000001613 neoplastic effect Effects 0.000 claims description 23
• 238000003776 cleavage reaction Methods 0.000 claims description 22
• 230000007017 scission Effects 0.000 claims description 22
• 238000011282 treatment Methods 0.000 claims description 22
• 238000004519 manufacturing process Methods 0.000 claims description 20
• 241000124008 Mammalia Species 0.000 claims description 17
• 239000007787 solid Substances 0.000 claims description 17
• 238000001514 detection method Methods 0.000 claims description 15
• 108020004999 messenger RNA Proteins 0.000 claims description 15
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 14
• 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 14
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 14
• 210000001124 body fluid Anatomy 0.000 claims description 14
• 239000010839 body fluid Substances 0.000 claims description 14
• 239000013604 expression vector Substances 0.000 claims description 13
• 238000000746 purification Methods 0.000 claims description 13
• 230000008685 targeting Effects 0.000 claims description 13
• 230000008859 change Effects 0.000 claims description 12
• 108091034117 Oligonucleotide Proteins 0.000 claims description 11
• 239000002246 antineoplastic agent Substances 0.000 claims description 11
• 210000002307 prostate Anatomy 0.000 claims description 11
• 108020004705 Codon Proteins 0.000 claims description 10
• 230000000692 anti-sense effect Effects 0.000 claims description 10
• 230000001580 bacterial effect Effects 0.000 claims description 10
• 230000012010 growth Effects 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 10
• 210000004072 lung Anatomy 0.000 claims description 10
• 230000005751 tumor progression Effects 0.000 claims description 10
• 210000000481 breast Anatomy 0.000 claims description 9
• 238000002955 isolation Methods 0.000 claims description 9
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 8
• 210000003000 inclusion body Anatomy 0.000 claims description 8
• 230000003211 malignant effect Effects 0.000 claims description 8
• 210000004962 mammalian cell Anatomy 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 150000003384 small molecules Chemical class 0.000 claims description 8
• 208000026310 Breast neoplasm Diseases 0.000 claims description 7
• 241000588724 Escherichia coli Species 0.000 claims description 7
• 206010061309 Neoplasm progression Diseases 0.000 claims description 7
• 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 claims description 7
• 239000012530 fluid Substances 0.000 claims description 7
• 241000238631 Hexapoda Species 0.000 claims description 6
• 239000008280 blood Substances 0.000 claims description 6
• 210000001072 colon Anatomy 0.000 claims description 6
• 210000003527 eukaryotic cell Anatomy 0.000 claims description 6
• 230000001575 pathological effect Effects 0.000 claims description 6
• 239000000816 peptidomimetic Substances 0.000 claims description 6
• 102100037942 Suppressor of tumorigenicity 14 protein Human genes 0.000 claims description 5
• 239000012472 biological sample Substances 0.000 claims description 5
• 210000004369 blood Anatomy 0.000 claims description 5
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 5
• 230000002255 enzymatic effect Effects 0.000 claims description 5
• 230000000977 initiatory effect Effects 0.000 claims description 5
• 238000012544 monitoring process Methods 0.000 claims description 5
• 210000001672 ovary Anatomy 0.000 claims description 5
• 230000028327 secretion Effects 0.000 claims description 5
• 210000002700 urine Anatomy 0.000 claims description 5
• 210000005253 yeast cell Anatomy 0.000 claims description 5
• 241000235648 Pichia Species 0.000 claims description 4
• 239000012190 activator Substances 0.000 claims description 4
• 210000004102 animal cell Anatomy 0.000 claims description 4
• 230000001772 anti-angiogenic effect Effects 0.000 claims description 4
• 239000000074 antisense oligonucleotide Substances 0.000 claims description 4
• 238000012230 antisense oligonucleotides Methods 0.000 claims description 4
• 229930014626 natural product Natural products 0.000 claims description 4
• 210000001236 prokaryotic cell Anatomy 0.000 claims description 4
• 210000003296 saliva Anatomy 0.000 claims description 4
• 210000004243 sweat Anatomy 0.000 claims description 4
• 210000001179 synovial fluid Anatomy 0.000 claims description 4
• 230000009261 transgenic effect Effects 0.000 claims description 4
• 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 3
• 206010003445 Ascites Diseases 0.000 claims description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 3
• 210000003679 cervix uteri Anatomy 0.000 claims description 3
• 210000000805 cytoplasm Anatomy 0.000 claims description 3
• 238000006471 dimerization reaction Methods 0.000 claims description 3
• 238000002744 homologous recombination Methods 0.000 claims description 3
• 230000006801 homologous recombination Effects 0.000 claims description 3
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 3
• 208000006994 Precancerous Conditions Diseases 0.000 claims description 2
• 101710098606 Suppressor of tumorigenicity 14 protein homolog Proteins 0.000 claims description 2
• 210000003722 extracellular fluid Anatomy 0.000 claims description 2
• 238000002743 insertional mutagenesis Methods 0.000 claims description 2
• 230000003902 lesion Effects 0.000 claims description 2
• 230000036210 malignancy Effects 0.000 claims description 2
• 210000001138 tear Anatomy 0.000 claims description 2
• 230000000259 anti-tumor effect Effects 0.000 claims 3
• 238000012258 culturing Methods 0.000 claims 2
• WPVINHLVHHPBMK-ULQDDVLXSA-N (2s)-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide Chemical compound C([C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)CCN1C(=O)[C@@H]1CCC(=O)N1 WPVINHLVHHPBMK-ULQDDVLXSA-N 0.000 claims 1
• 208000005443 Circulating Neoplastic Cells Diseases 0.000 claims 1
• 238000001574 biopsy Methods 0.000 claims 1
• 239000003593 chromogenic compound Substances 0.000 claims 1
• 239000001963 growth medium Substances 0.000 claims 1
• 102000035195 Peptidases Human genes 0.000 description 228
• 235000019419 proteases Nutrition 0.000 description 208
• 102000004169 proteins and genes Human genes 0.000 description 205
• 235000018102 proteins Nutrition 0.000 description 198
• 108020004414 DNA Proteins 0.000 description 82
• 230000014509 gene expression Effects 0.000 description 76
• 229940024606 amino acid Drugs 0.000 description 68
• 238000003556 assay Methods 0.000 description 58
• 210000004881 tumor cell Anatomy 0.000 description 41
• 230000009368 gene silencing by RNA Effects 0.000 description 35
• 239000000203 mixture Substances 0.000 description 34
• 108091030071 RNAI Proteins 0.000 description 31
• 238000000338 in vitro Methods 0.000 description 30
• 239000000047 product Substances 0.000 description 28
• 125000003275 alpha amino acid group Chemical group 0.000 description 25
• 238000012216 screening Methods 0.000 description 25
• -1 small molecules Chemical class 0.000 description 24
• 239000003446 ligand Substances 0.000 description 23
• 102000004190 Enzymes Human genes 0.000 description 22
• 108090000790 Enzymes Proteins 0.000 description 22
• 229940088598 enzyme Drugs 0.000 description 22
• 239000003001 serine protease inhibitor Substances 0.000 description 22
• 230000033115 angiogenesis Effects 0.000 description 20
• 102000005962 receptors Human genes 0.000 description 20
• 108020003175 receptors Proteins 0.000 description 20
• 206010027476 Metastases Diseases 0.000 description 19
• 239000013612 plasmid Substances 0.000 description 18
• 230000009401 metastasis Effects 0.000 description 17
• 101710102218 Serine protease inhibitor Proteins 0.000 description 16
• 229940122055 Serine protease inhibitor Drugs 0.000 description 16
• 238000009396 hybridization Methods 0.000 description 16
• 239000013615 primer Substances 0.000 description 16
• 239000002299 complementary DNA Substances 0.000 description 15
• 238000001727 in vivo Methods 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• 108010076504 Protein Sorting Signals Proteins 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 14
• 208000035475 disorder Diseases 0.000 description 14
• 230000006870 function Effects 0.000 description 13
• 238000013518 transcription Methods 0.000 description 13
• 230000035897 transcription Effects 0.000 description 13
• 230000004071 biological effect Effects 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 239000000284 extract Substances 0.000 description 12
• 125000005647 linker group Chemical group 0.000 description 12
• 210000004882 non-tumor cell Anatomy 0.000 description 12
• 208000024891 symptom Diseases 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• 239000002987 primer (paints) Substances 0.000 description 11
• 230000017854 proteolysis Effects 0.000 description 11
• 241000894007 species Species 0.000 description 11
• 238000010561 standard procedure Methods 0.000 description 11
• 108091028043 Nucleic acid sequence Proteins 0.000 description 10
• 238000011161 development Methods 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 230000005714 functional activity Effects 0.000 description 10
• 230000014616 translation Effects 0.000 description 10
• 108060003951 Immunoglobulin Proteins 0.000 description 9
• 206010029113 Neovascularisation Diseases 0.000 description 9
• 206010060862 Prostate cancer Diseases 0.000 description 9
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 9
• 238000004458 analytical method Methods 0.000 description 9
• 230000018109 developmental process Effects 0.000 description 9
• 102000018358 immunoglobulin Human genes 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 238000007423 screening assay Methods 0.000 description 9
• 238000013519 translation Methods 0.000 description 9
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
• 241000196324 Embryophyta Species 0.000 description 8
• 241000282412 Homo Species 0.000 description 8
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 8
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 8
• 108020004511 Recombinant DNA Proteins 0.000 description 8
• 241000700605 Viruses Species 0.000 description 8
• 230000015556 catabolic process Effects 0.000 description 8
• 230000001413 cellular effect Effects 0.000 description 8
• 238000010369 molecular cloning Methods 0.000 description 8
• 239000002157 polynucleotide Substances 0.000 description 8
• 102000040430 polynucleotide Human genes 0.000 description 8
• 108091033319 polynucleotide Proteins 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 230000001105 regulatory effect Effects 0.000 description 8
• 230000019491 signal transduction Effects 0.000 description 8
• 108091026890 Coding region Proteins 0.000 description 7
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 7
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 7
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 210000002744 extracellular matrix Anatomy 0.000 description 7
• 239000003102 growth factor Substances 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 210000004379 membrane Anatomy 0.000 description 7
• 239000012528 membrane Substances 0.000 description 7
• 230000004048 modification Effects 0.000 description 7
• 238000012986 modification Methods 0.000 description 7
• 238000000159 protein binding assay Methods 0.000 description 7
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 7
• 230000009870 specific binding Effects 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
• 206010006187 Breast cancer Diseases 0.000 description 6
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 6
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
• 108700026244 Open Reading Frames Proteins 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 6
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 6
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 6
• 230000000890 antigenic effect Effects 0.000 description 6
• 229940098773 bovine serum albumin Drugs 0.000 description 6
• 230000009400 cancer invasion Effects 0.000 description 6
• 208000029742 colonic neoplasm Diseases 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 238000006731 degradation reaction Methods 0.000 description 6
• 210000004408 hybridoma Anatomy 0.000 description 6
• 230000009545 invasion Effects 0.000 description 6
• 239000003550 marker Substances 0.000 description 6
• 102000006240 membrane receptors Human genes 0.000 description 6
• 238000003752 polymerase chain reaction Methods 0.000 description 6
• 241000972773 Aulopiformes Species 0.000 description 5
• 108010001857 Cell Surface Receptors Proteins 0.000 description 5
• 238000002965 ELISA Methods 0.000 description 5
• 101001008919 Homo sapiens Kallikrein-10 Proteins 0.000 description 5
• 102100027613 Kallikrein-10 Human genes 0.000 description 5
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
• BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 5
• 206010061535 Ovarian neoplasm Diseases 0.000 description 5
• 108010072866 Prostate-Specific Antigen Proteins 0.000 description 5
• 102100038358 Prostate-specific antigen Human genes 0.000 description 5
• 108700008625 Reporter Genes Proteins 0.000 description 5
• 206010064390 Tumour invasion Diseases 0.000 description 5
• 230000004075 alteration Effects 0.000 description 5
• 125000000539 amino acid group Chemical group 0.000 description 5
• 210000002469 basement membrane Anatomy 0.000 description 5
• 210000004899 c-terminal region Anatomy 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 238000010367 cloning Methods 0.000 description 5
• 238000013461 design Methods 0.000 description 5
• 230000029087 digestion Effects 0.000 description 5
• 230000002538 fungal effect Effects 0.000 description 5
• 230000004927 fusion Effects 0.000 description 5
• 108020001507 fusion proteins Proteins 0.000 description 5
• 102000037865 fusion proteins Human genes 0.000 description 5
• 238000013537 high throughput screening Methods 0.000 description 5
• 230000003053 immunization Effects 0.000 description 5
• 238000000099 in vitro assay Methods 0.000 description 5
• 208000020816 lung neoplasm Diseases 0.000 description 5
• 108010082117 matrigel Proteins 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 108091008146 restriction endonucleases Proteins 0.000 description 5
• 235000019515 salmon Nutrition 0.000 description 5
• 230000002103 transcriptional effect Effects 0.000 description 5
• 230000005748 tumor development Effects 0.000 description 5
• 230000004614 tumor growth Effects 0.000 description 5
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• 241000283690 Bos taurus Species 0.000 description 4
• 208000005623 Carcinogenesis Diseases 0.000 description 4
• 108090000317 Chymotrypsin Proteins 0.000 description 4
• 229920001917 Ficoll Polymers 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 4
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 4
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• 108010067902 Peptide Library Proteins 0.000 description 4
• 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 4
• 241000283984 Rodentia Species 0.000 description 4
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
• SRXKIZXIRHMPFW-UHFFFAOYSA-N [4-[6-[amino(azaniumylidene)methyl]naphthalen-2-yl]oxycarbonylphenyl]-(diaminomethylidene)azanium;methanesulfonate Chemical compound CS([O-])(=O)=O.CS([O-])(=O)=O.C1=CC(N=C([NH3+])N)=CC=C1C(=O)OC1=CC=C(C=C(C=C2)C([NH3+])=N)C2=C1 SRXKIZXIRHMPFW-UHFFFAOYSA-N 0.000 description 4
• 230000001594 aberrant effect Effects 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 239000000427 antigen Substances 0.000 description 4
• 108091007433 antigens Proteins 0.000 description 4
• 102000036639 antigens Human genes 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• 210000004204 blood vessel Anatomy 0.000 description 4
• 230000036952 cancer formation Effects 0.000 description 4
• 231100000504 carcinogenesis Toxicity 0.000 description 4
• 238000006555 catalytic reaction Methods 0.000 description 4
• 229960002376 chymotrypsin Drugs 0.000 description 4
• 239000013599 cloning vector Substances 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 238000012217 deletion Methods 0.000 description 4
• 230000037430 deletion Effects 0.000 description 4
• 238000007876 drug discovery Methods 0.000 description 4
• 238000011156 evaluation Methods 0.000 description 4
• 239000000499 gel Substances 0.000 description 4
• 230000002068 genetic effect Effects 0.000 description 4
• 150000004676 glycans Chemical class 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 238000002649 immunization Methods 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 238000003780 insertion Methods 0.000 description 4
• 230000037431 insertion Effects 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 238000002372 labelling Methods 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 239000011159 matrix material Substances 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 229950009865 nafamostat Drugs 0.000 description 4
• 238000011275 oncology therapy Methods 0.000 description 4
• 238000010647 peptide synthesis reaction Methods 0.000 description 4
• 238000002823 phage display Methods 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• 229920001282 polysaccharide Polymers 0.000 description 4
• 239000005017 polysaccharide Substances 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 238000012552 review Methods 0.000 description 4
• 150000003839 salts Chemical class 0.000 description 4
• 239000007790 solid phase Substances 0.000 description 4
• FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 3
• SUGXUUGGLDCZKB-UHFFFAOYSA-N 3,4-dichloroisocoumarin Chemical compound C1=CC=C2C(Cl)=C(Cl)OC(=O)C2=C1 SUGXUUGGLDCZKB-UHFFFAOYSA-N 0.000 description 3
• 241000283707 Capra Species 0.000 description 3
• 241000282994 Cervidae Species 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 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 3
• 241000724791 Filamentous phage Species 0.000 description 3
• 108090001101 Hepsin Proteins 0.000 description 3
• 102000004989 Hepsin Human genes 0.000 description 3
• 101710132360 Kunitz-type serine protease inhibitor Proteins 0.000 description 3
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
• 108010091175 Matriptase Proteins 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 206010033128 Ovarian cancer Diseases 0.000 description 3
• 108090000526 Papain Proteins 0.000 description 3
• 241001494479 Pecora Species 0.000 description 3
• 241000282849 Ruminantia Species 0.000 description 3
• 238000012300 Sequence Analysis Methods 0.000 description 3
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
• 241000282887 Suidae Species 0.000 description 3
• FKMJXALNHKIDOD-LBPRGKRZSA-N TAMe Chemical compound NC(=N)NCCC[C@@H](C(=O)OC)NS(=O)(=O)C1=CC=C(C)C=C1 FKMJXALNHKIDOD-LBPRGKRZSA-N 0.000 description 3
• 108090000631 Trypsin Proteins 0.000 description 3
• 102000004142 Trypsin Human genes 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 239000002870 angiogenesis inducing agent Substances 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 230000003527 anti-angiogenesis Effects 0.000 description 3
• 238000011394 anticancer treatment Methods 0.000 description 3
• 210000004507 artificial chromosome Anatomy 0.000 description 3
• 238000002820 assay format Methods 0.000 description 3
• 238000000376 autoradiography Methods 0.000 description 3
• 239000013060 biological fluid Substances 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 108091092328 cellular RNA Proteins 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 238000004590 computer program Methods 0.000 description 3
• 239000000470 constituent Substances 0.000 description 3
• 230000009089 cytolysis Effects 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 230000013595 glycosylation Effects 0.000 description 3
• 238000006206 glycosylation reaction Methods 0.000 description 3
• 230000001900 immune effect Effects 0.000 description 3
• 230000028993 immune response Effects 0.000 description 3
• 230000002163 immunogen Effects 0.000 description 3
• 230000005847 immunogenicity Effects 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 201000005296 lung carcinoma Diseases 0.000 description 3
• 210000004698 lymphocyte Anatomy 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 229910021645 metal ion Inorganic materials 0.000 description 3
• 238000002703 mutagenesis Methods 0.000 description 3
• 231100000350 mutagenesis Toxicity 0.000 description 3
• 229940055729 papain Drugs 0.000 description 3
• 235000019834 papain Nutrition 0.000 description 3
• 230000003652 pro-growth Effects 0.000 description 3
• 230000004952 protein activity Effects 0.000 description 3
• 239000000376 reactant Substances 0.000 description 3
• 230000010076 replication Effects 0.000 description 3
• 210000002966 serum Anatomy 0.000 description 3
• 229910001415 sodium ion Inorganic materials 0.000 description 3
• 230000002194 synthesizing effect Effects 0.000 description 3
• 238000011285 therapeutic regimen Methods 0.000 description 3
• 239000012588 trypsin Substances 0.000 description 3
• 229960001322 trypsin Drugs 0.000 description 3
• 239000000439 tumor marker Substances 0.000 description 3
• 241001515965 unidentified phage Species 0.000 description 3
• 210000005166 vasculature Anatomy 0.000 description 3
• 235000012431 wafers Nutrition 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• SNDPXSYFESPGGJ-UHFFFAOYSA-N 2-aminopentanoic acid Chemical compound CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
• 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• 108010078791 Carrier Proteins Proteins 0.000 description 2
• 229920000742 Cotton Polymers 0.000 description 2
• 108010069514 Cyclic Peptides Proteins 0.000 description 2
• 102000001189 Cyclic Peptides Human genes 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
• 241000701832 Enterobacteria phage T3 Species 0.000 description 2
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 241000287828 Gallus gallus Species 0.000 description 2
• 102100033299 Glia-derived nexin Human genes 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 101000598058 Homo sapiens Transmembrane protease serine 11D Proteins 0.000 description 2
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 108010059912 LEX 032 Proteins 0.000 description 2
• 108010085895 Laminin Proteins 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 102000018697 Membrane Proteins Human genes 0.000 description 2
• 108010052285 Membrane Proteins Proteins 0.000 description 2
• 102000005741 Metalloproteases Human genes 0.000 description 2
• 108010006035 Metalloproteases Proteins 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
• 101100069392 Mus musculus Gzma gene Proteins 0.000 description 2
• MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 2
• 102100037591 Neuroserpin Human genes 0.000 description 2
• 101100386053 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-3 gene Proteins 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 102000003840 Opioid Receptors Human genes 0.000 description 2
• 108090000137 Opioid Receptors Proteins 0.000 description 2
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
• 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
• 102000057297 Pepsin A Human genes 0.000 description 2
• 108090000284 Pepsin A Proteins 0.000 description 2
• 102000007079 Peptide Fragments Human genes 0.000 description 2
• 108010033276 Peptide Fragments Proteins 0.000 description 2
• 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
• 108091081021 Sense strand Proteins 0.000 description 2
• 101710107115 Serine protease inhibitor 3 Proteins 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 108090000190 Thrombin Proteins 0.000 description 2
• 241000700618 Vaccinia virus Species 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000021736 acetylation Effects 0.000 description 2
• 238000006640 acetylation reaction Methods 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 238000007792 addition Methods 0.000 description 2
• 108010091628 alpha 1-Antichymotrypsin Proteins 0.000 description 2
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 2
• 230000001668 ameliorated effect Effects 0.000 description 2
• 239000012491 analyte Substances 0.000 description 2
• 239000003098 androgen Substances 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 229940034982 antineoplastic agent Drugs 0.000 description 2
• 229940041181 antineoplastic drug Drugs 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 230000004888 barrier function Effects 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
• 230000003115 biocidal effect Effects 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 229920001222 biopolymer Polymers 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• FSEKIHNIDBATFG-UHFFFAOYSA-N camostat mesylate Chemical compound CS([O-])(=O)=O.C1=CC(CC(=O)OCC(=O)N(C)C)=CC=C1OC(=O)C1=CC=C([NH+]=C(N)N)C=C1 FSEKIHNIDBATFG-UHFFFAOYSA-N 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 235000013330 chicken meat Nutrition 0.000 description 2
• 210000003711 chorioallantoic membrane Anatomy 0.000 description 2
• 238000010276 construction Methods 0.000 description 2
• 239000012228 culture supernatant Substances 0.000 description 2
• XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• 230000003413 degradative effect Effects 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 238000001085 differential centrifugation Methods 0.000 description 2
• 238000007878 drug screening assay Methods 0.000 description 2
• 239000012636 effector Substances 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• 238000001952 enzyme assay Methods 0.000 description 2
• 210000000981 epithelium Anatomy 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 230000007717 exclusion Effects 0.000 description 2
• 238000002060 fluorescence correlation spectroscopy Methods 0.000 description 2
• 238000002875 fluorescence polarization Methods 0.000 description 2
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 230000001456 gonadotroph Effects 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 102000014108 human airway trypsin-like protease Human genes 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 230000001965 increasing effect Effects 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 238000011081 inoculation Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000005342 ion exchange Methods 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 150000002611 lead compounds Chemical class 0.000 description 2
• 230000004807 localization Effects 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 210000001165 lymph node Anatomy 0.000 description 2
• 235000018977 lysine Nutrition 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229950002475 mesilate Drugs 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 230000001394 metastastic effect Effects 0.000 description 2
• 230000006510 metastatic growth Effects 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 230000003278 mimic effect Effects 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 229960005181 morphine Drugs 0.000 description 2
• 108010080874 neuroserpin Proteins 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 210000003463 organelle Anatomy 0.000 description 2
• 229960003104 ornithine Drugs 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 229940111202 pepsin Drugs 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000037452 priming Effects 0.000 description 2
• 230000001023 pro-angiogenic effect Effects 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 208000023958 prostate neoplasm Diseases 0.000 description 2
• 230000007065 protein hydrolysis Effects 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 238000002165 resonance energy transfer Methods 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
• 238000002821 scintillation proximity assay Methods 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 238000012163 sequencing technique Methods 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 230000002269 spontaneous effect Effects 0.000 description 2
• 238000012289 standard assay Methods 0.000 description 2
• 238000010254 subcutaneous injection Methods 0.000 description 2
• 239000007929 subcutaneous injection Substances 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 229960004072 thrombin Drugs 0.000 description 2
• 108010016054 tissue-factor-pathway inhibitor 2 Proteins 0.000 description 2
• 102000055046 tissue-factor-pathway inhibitor 2 Human genes 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000005026 transcription initiation Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• 206010046766 uterine cancer Diseases 0.000 description 2
• 229960005486 vaccine Drugs 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 238000001086 yeast two-hybrid system Methods 0.000 description 2
• BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
• MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 1
• NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 1
• ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
• QSLFDILMORXPKP-UHFFFAOYSA-N (3-methylimidazol-3-ium-1-yl)-methylsulfanylphosphinate Chemical compound CSP([O-])(=O)N1C=C[N+](C)=C1 QSLFDILMORXPKP-UHFFFAOYSA-N 0.000 description 1
• PKBZGVVSSNNHGY-INTLEYBYSA-N (4-carbamimidoylphenyl) 4-[(e)-3-[(2-ethoxy-2-oxoethyl)-prop-2-enylamino]-2-methyl-3-oxoprop-1-enyl]benzoate;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(/C=C(\C)C(=O)N(CC=C)CC(=O)OCC)=CC=C1C(=O)OC1=CC=C(C(N)=N)C=C1 PKBZGVVSSNNHGY-INTLEYBYSA-N 0.000 description 1
• ICYICMXERRTCPY-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) 4-(4,5-dihydro-1h-imidazol-2-ylamino)benzoate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.C1=CC2=CC(C(=N)N)=CC=C2C=C1OC(=O)C(C=C1)=CC=C1NC1=NCCN1 ICYICMXERRTCPY-UHFFFAOYSA-N 0.000 description 1
• GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
• OWIZTYOMGVTSDP-TXOOBNKBSA-N (e)-3-[4-(imidazol-1-ylmethyl)phenyl]prop-2-enoic acid;hydrate;hydrochloride Chemical compound O.Cl.C1=CC(/C=C/C(=O)O)=CC=C1CN1C=NC=C1 OWIZTYOMGVTSDP-TXOOBNKBSA-N 0.000 description 1
• VYEWZWBILJHHCU-OMQUDAQFSA-N (e)-n-[(2s,3r,4r,5r,6r)-2-[(2r,3r,4s,5s,6s)-3-acetamido-5-amino-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[2-[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl]-4,5-dihydroxyoxan-3-yl]-5-methylhex-2-enamide Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)C(O)C[C@@H]2[C@H](O)[C@H](O)[C@H]([C@@H](O2)O[C@@H]2[C@@H]([C@@H](O)[C@H](N)[C@@H](CO)O2)NC(C)=O)NC(=O)/C=C/CC(C)C)C=CC(=O)NC1=O VYEWZWBILJHHCU-OMQUDAQFSA-N 0.000 description 1
• UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
• 101150090724 3 gene Proteins 0.000 description 1
• WPANETAWYGDRLL-UHFFFAOYSA-N 4-aminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C=C1 WPANETAWYGDRLL-UHFFFAOYSA-N 0.000 description 1
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
• JMHFFDIMOUKDCZ-NTXHZHDSSA-N 61214-51-5 Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CC=CC=C1 JMHFFDIMOUKDCZ-NTXHZHDSSA-N 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
• 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
• 101710163968 Antistasin Proteins 0.000 description 1
• 102000004411 Antithrombin III Human genes 0.000 description 1
• 108090000935 Antithrombin III Proteins 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 108010031480 Artificial Receptors Proteins 0.000 description 1
• IIFDPDVJAHQFSR-WHFBIAKZSA-N Asn-Glu Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O IIFDPDVJAHQFSR-WHFBIAKZSA-N 0.000 description 1
• JHFNSBBHKSZXKB-VKHMYHEASA-N Asp-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(O)=O JHFNSBBHKSZXKB-VKHMYHEASA-N 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 102100037293 Atrial natriuretic peptide-converting enzyme Human genes 0.000 description 1
• 101710133555 Atrial natriuretic peptide-converting enzyme Proteins 0.000 description 1
• 241001367049 Autographa Species 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 108090001008 Avidin Proteins 0.000 description 1
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 102400000748 Beta-endorphin Human genes 0.000 description 1
• 101800005049 Beta-endorphin Proteins 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• 238000011740 C57BL/6 mouse Methods 0.000 description 1
• 102000000584 Calmodulin Human genes 0.000 description 1
• 108010041952 Calmodulin Proteins 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 101710169873 Capsid protein G8P Proteins 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 241000701489 Cauliflower mosaic virus Species 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 241000766026 Coregonus nasus Species 0.000 description 1
• 241000186216 Corynebacterium Species 0.000 description 1
• OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 1
• 239000003155 DNA primer Substances 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
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 108090000204 Dipeptidase 1 Proteins 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 101710194146 Ecotin Proteins 0.000 description 1
• 108010049140 Endorphins Proteins 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
• 241000701959 Escherichia virus Lambda Species 0.000 description 1
• 241001524679 Escherichia virus M13 Species 0.000 description 1
• 108010008177 Fd immunoglobulins Proteins 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
• 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 102000016359 Fibronectins Human genes 0.000 description 1
• 108090000331 Firefly luciferases Proteins 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 108010001515 Galectin 4 Proteins 0.000 description 1
• 102100039556 Galectin-4 Human genes 0.000 description 1
• XITLYYAIPBBHPX-ZKWXMUAHSA-N Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O XITLYYAIPBBHPX-ZKWXMUAHSA-N 0.000 description 1
• SXGAGTVDWKQYCX-BQBZGAKWSA-N Glu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O SXGAGTVDWKQYCX-BQBZGAKWSA-N 0.000 description 1
• 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
• 102000005720 Glutathione transferase Human genes 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical group NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 108060005986 Granzyme Proteins 0.000 description 1
• 102000001398 Granzyme Human genes 0.000 description 1
• 101710140489 Guamerin Proteins 0.000 description 1
• 108010043026 HGF activator Proteins 0.000 description 1
• 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
• 102100031465 Hepatocyte growth factor activator Human genes 0.000 description 1
• 208000028782 Hereditary disease Diseases 0.000 description 1
• MAJYPBAJPNUFPV-BQBZGAKWSA-N His-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MAJYPBAJPNUFPV-BQBZGAKWSA-N 0.000 description 1
• 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 description 1
• 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 1
• 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 1
• 101000798702 Homo sapiens Transmembrane protease serine 4 Proteins 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• 206010062767 Hypophysitis 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
• 206010061218 Inflammation Diseases 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 101800001691 Inter-alpha-trypsin inhibitor light chain Proteins 0.000 description 1
• 102400001240 Inter-alpha-trypsin inhibitor light chain Human genes 0.000 description 1
• 101710114613 Intracellular serine protease Proteins 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-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
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 108010054278 Lac Repressors Proteins 0.000 description 1
• 108090001090 Lectins Proteins 0.000 description 1
• 102000004856 Lectins Human genes 0.000 description 1
• 101710180643 Leishmanolysin Proteins 0.000 description 1
• URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 102000003960 Ligases Human genes 0.000 description 1
• 108090000364 Ligases Proteins 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 101710125418 Major capsid protein Proteins 0.000 description 1
• 101710156564 Major tail protein Gp23 Proteins 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 108010038049 Mating Factor Proteins 0.000 description 1
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
• 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
• 208000024556 Mendelian disease Diseases 0.000 description 1
• 241000579835 Merops Species 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 241000713333 Mouse mammary tumor virus Species 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 102100030856 Myoglobin Human genes 0.000 description 1
• 108010062374 Myoglobin Proteins 0.000 description 1
• PHSRRHGYXQCRPU-AWEZNQCLSA-N N-(3-oxododecanoyl)-L-homoserine lactone Chemical compound CCCCCCCCCC(=O)CC(=O)N[C@H]1CCOC1=O PHSRRHGYXQCRPU-AWEZNQCLSA-N 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• OAIDYCIOARUBNS-WNQIDUERSA-N OC[C@H](N)C(O)=O.C1=CC=C2C(=O)OC=CC2=C1 Chemical compound OC[C@H](N)C(O)=O.C1=CC=C2C(=O)OC=CC2=C1 OAIDYCIOARUBNS-WNQIDUERSA-N 0.000 description 1
• 102000043276 Oncogene Human genes 0.000 description 1
• 241000906034 Orthops Species 0.000 description 1
• 108090000417 Oxygenases Proteins 0.000 description 1
• 102000004020 Oxygenases Human genes 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• 108010038988 Peptide Hormones Proteins 0.000 description 1
• 102000015731 Peptide Hormones Human genes 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
• 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
• 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
• 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• BEPSGCXDIVACBU-IUCAKERBSA-N Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CN=CN1 BEPSGCXDIVACBU-IUCAKERBSA-N 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 102100037681 Protein FEV Human genes 0.000 description 1
• 101710198166 Protein FEV Proteins 0.000 description 1
• 108010067787 Proteoglycans Proteins 0.000 description 1
• 102000016611 Proteoglycans Human genes 0.000 description 1
• 239000013614 RNA sample Substances 0.000 description 1
• 230000006819 RNA synthesis Effects 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 108091028664 Ribonucleotide Proteins 0.000 description 1
• 108010003581 Ribulose-bisphosphate carboxylase Proteins 0.000 description 1
• 241000714474 Rous sarcoma virus Species 0.000 description 1
• 238000011579 SCID mouse model Methods 0.000 description 1
• 102000000395 SH3 domains Human genes 0.000 description 1
• 108050008861 SH3 domains Proteins 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 241000253973 Schistocerca gregaria Species 0.000 description 1
• 241000242683 Schistosoma haematobium Species 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• UJTZHGHXJKIAOS-WHFBIAKZSA-N Ser-Gln Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O UJTZHGHXJKIAOS-WHFBIAKZSA-N 0.000 description 1
• LZLREEUGSYITMX-JQWIXIFHSA-N Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)N)C(O)=O)=CNC2=C1 LZLREEUGSYITMX-JQWIXIFHSA-N 0.000 description 1
• 108010005113 Serpin E2 Proteins 0.000 description 1
• 108091081024 Start codon Proteins 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• DSGIVWSDDRDJIO-ZXXMMSQZSA-N Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DSGIVWSDDRDJIO-ZXXMMSQZSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 108010000499 Thromboplastin Proteins 0.000 description 1
• 102000002262 Thromboplastin Human genes 0.000 description 1
• 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• RDFCSSHDJSZMTQ-ZDUSSCGKSA-N Tos-Lys-CH2Cl Chemical compound CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 RDFCSSHDJSZMTQ-ZDUSSCGKSA-N 0.000 description 1
• 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
• 102100032471 Transmembrane protease serine 4 Human genes 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
• 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
• YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
• ZSXJENBJGRHKIG-UWVGGRQHSA-N Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ZSXJENBJGRHKIG-UWVGGRQHSA-N 0.000 description 1
• JAQGKXUEKGKTKX-HOTGVXAUSA-N Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 JAQGKXUEKGKTKX-HOTGVXAUSA-N 0.000 description 1
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 101150117115 V gene Proteins 0.000 description 1
• 108010059993 Vancomycin Proteins 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 210000003815 abdominal wall Anatomy 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 208000037919 acquired disease Diseases 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001780 adrenocortical effect Effects 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 230000009824 affinity maturation Effects 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 238000003314 affinity selection Methods 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
• 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
• 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 1
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229960000711 alprostadil Drugs 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• 210000004381 amniotic fluid Anatomy 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 238000004873 anchoring Methods 0.000 description 1
• RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical class C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000002788 anti-peptide Effects 0.000 description 1
• 230000009830 antibody antigen interaction Effects 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229960005348 antithrombin iii Drugs 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 108010047857 aspartylglycine Proteins 0.000 description 1
• 238000005284 basis set Methods 0.000 description 1
• 108010065944 bdellastasin Proteins 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
• 102000006635 beta-lactamase Human genes 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000008238 biochemical pathway Effects 0.000 description 1
• 230000003851 biochemical process Effects 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 230000006287 biotinylation Effects 0.000 description 1
• 238000007413 biotinylation Methods 0.000 description 1
• 230000023555 blood coagulation Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 210000004900 c-terminal fragment Anatomy 0.000 description 1
• 229960000772 camostat Drugs 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 238000001386 capillary affinity electrophoresis Methods 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000004709 cell invasion Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 238000012412 chemical coupling Methods 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000007806 chemical reaction intermediate Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 239000013626 chemical specie Substances 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 210000003837 chick embryo Anatomy 0.000 description 1
• WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
• 229960005091 chloramphenicol Drugs 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 229940043292 chymotrypsin / trypsin Drugs 0.000 description 1
• 229960002173 citrulline Drugs 0.000 description 1
• 235000013477 citrulline Nutrition 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 238000002742 combinatorial mutagenesis Methods 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 238000003271 compound fluorescence assay Methods 0.000 description 1
• 239000003636 conditioned culture medium Substances 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 108010075231 contrapsin Proteins 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000011613 copenhagen rat Methods 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 108010004073 cysteinylcysteine Proteins 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000000593 degrading effect Effects 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• 239000005547 deoxyribonucleotide Substances 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000014155 detection of activity Effects 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 229960000633 dextran sulfate Drugs 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229940000406 drug candidate Drugs 0.000 description 1
• 230000036267 drug metabolism Effects 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000009144 enzymatic modification Effects 0.000 description 1
• 238000001976 enzyme digestion Methods 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000010408 film Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 210000001559 fluids and secretion Anatomy 0.000 description 1
• 238000000198 fluorescence anisotropy Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 229960005051 fluostigmine Drugs 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 238000010230 functional analysis Methods 0.000 description 1
• 229950000501 gabexate Drugs 0.000 description 1
• DNTNDFLIKUKKOC-UHFFFAOYSA-N gabexate methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=C(OC(=O)CCCCCN=C(N)[NH3+])C=C1 DNTNDFLIKUKKOC-UHFFFAOYSA-N 0.000 description 1
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000004077 genetic alteration Effects 0.000 description 1
• 231100000118 genetic alteration Toxicity 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 108010079547 glutamylmethionine Proteins 0.000 description 1
• 210000004368 gonadotroph Anatomy 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 238000012188 high-throughput screening assay Methods 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• 229920001519 homopolymer Polymers 0.000 description 1
• 108091008039 hormone receptors Proteins 0.000 description 1
• 238000002657 hormone replacement therapy Methods 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 210000003016 hypothalamus Anatomy 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 230000014726 immortalization of host cell Effects 0.000 description 1
• 229940127121 immunoconjugate Drugs 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 239000012133 immunoprecipitate Substances 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 238000001155 isoelectric focusing 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
• 230000000155 isotopic effect Effects 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 230000001689 kallikreinlike Effects 0.000 description 1
• 108010079923 lambda Spi-1 Proteins 0.000 description 1
• 230000002045 lasting effect Effects 0.000 description 1
• 239000002523 lectin Substances 0.000 description 1
• 230000004576 lipid-binding Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007791 liquid phase Substances 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 238000000504 luminescence detection Methods 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 208000037841 lung tumor Diseases 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 210000001365 lymphatic vessel Anatomy 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 230000001320 lysogenic effect Effects 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 210000000723 mammalian artificial chromosome Anatomy 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• SKEFKEOTNIPLCQ-LWIQTABASA-N mating hormone Chemical group C([C@@H](C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCS(C)=O)C(=O)NC(CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CN=CN1 SKEFKEOTNIPLCQ-LWIQTABASA-N 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 108020004084 membrane receptors Proteins 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical class CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 108010065781 myosin light chain 2 Proteins 0.000 description 1
• YFCUZWYIPBUQBD-ZOWNYOTGSA-N n-[(3s)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide;hydron;chloride Chemical compound Cl.CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 YFCUZWYIPBUQBD-ZOWNYOTGSA-N 0.000 description 1
• 210000004898 n-terminal fragment Anatomy 0.000 description 1
• 210000005170 neoplastic cell Anatomy 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 210000000944 nerve tissue Anatomy 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 231100001221 nontumorigenic Toxicity 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 238000011580 nude mouse model Methods 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 238000002515 oligonucleotide synthesis Methods 0.000 description 1
• 101150093139 ompT gene Proteins 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 229950003837 ozagrel Drugs 0.000 description 1
• 239000005022 packaging material Substances 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 239000000813 peptide hormone Substances 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 229960005190 phenylalanine Drugs 0.000 description 1
• 108010079892 phosphoglycerol kinase Proteins 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000000243 photosynthetic effect Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 108090000102 pigment epithelium-derived factor Proteins 0.000 description 1
• 210000003635 pituitary gland Anatomy 0.000 description 1
• 230000003169 placental effect Effects 0.000 description 1
• 210000002381 plasma Anatomy 0.000 description 1
• 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920000447 polyanionic polymer Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000005373 porous glass Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 230000009465 prokaryotic expression Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 201000001514 prostate carcinoma Diseases 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 239000003531 protein hydrolysate Substances 0.000 description 1
• 238000001814 protein method Methods 0.000 description 1
• 238000002005 protein protein interaction detection Methods 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 238000000734 protein sequencing Methods 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 238000002762 protein-protein interaction assay Methods 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 229940124553 radioprotectant Drugs 0.000 description 1
• 230000003439 radiotherapeutic effect Effects 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 108700024098 rat LOC299282 Proteins 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 239000003488 releasing hormone Substances 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 239000012508 resin bead Substances 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 239000002336 ribonucleotide Substances 0.000 description 1
• 125000002652 ribonucleotide group Chemical group 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000010008 shearing Methods 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 238000004557 single molecule detection Methods 0.000 description 1
• 238000002741 site-directed mutagenesis Methods 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 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
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 238000003746 solid phase reaction Methods 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 125000006850 spacer group Chemical group 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 108091007196 stromelysin Proteins 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 230000007838 tissue remodeling Effects 0.000 description 1
• 101150009136 tlcA gene Proteins 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000014621 translational initiation Effects 0.000 description 1
• 239000001226 triphosphate Substances 0.000 description 1
• 235000011178 triphosphate Nutrition 0.000 description 1
• 208000025421 tumor of uterus Diseases 0.000 description 1
• MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 108010003137 tyrosyltyrosine Proteins 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241000701366 unidentified nuclear polyhedrosis viruses Species 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 229960005356 urokinase Drugs 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
• 229960003165 vancomycin Drugs 0.000 description 1
• MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000007998 vessel formation Effects 0.000 description 1
• 210000000605 viral structure Anatomy 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1