JP2017515466A - 治療用として改善された特性を有するβ−ラクタマーゼ - Google Patents
治療用として改善された特性を有するβ−ラクタマーゼ Download PDFInfo
- Publication number
- JP2017515466A JP2017515466A JP2016562248A JP2016562248A JP2017515466A JP 2017515466 A JP2017515466 A JP 2017515466A JP 2016562248 A JP2016562248 A JP 2016562248A JP 2016562248 A JP2016562248 A JP 2016562248A JP 2017515466 A JP2017515466 A JP 2017515466A
- Authority
- JP
- Japan
- Prior art keywords
- lactamase
- residue
- hydrophilic
- amino acid
- hydrophobic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000006635 beta-lactamase Human genes 0.000 title claims abstract description 243
- 108090000204 Dipeptidase 1 Proteins 0.000 title claims abstract description 177
- 230000001225 therapeutic effect Effects 0.000 title description 12
- 238000000034 method Methods 0.000 claims abstract description 80
- 239000000203 mixture Substances 0.000 claims abstract description 67
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 64
- 102000004190 Enzymes Human genes 0.000 claims abstract description 46
- 108090000790 Enzymes Proteins 0.000 claims abstract description 46
- 206010009657 Clostridium difficile colitis Diseases 0.000 claims abstract description 43
- 208000037384 Clostridium Infections Diseases 0.000 claims abstract description 39
- 206010054236 Clostridium difficile infection Diseases 0.000 claims abstract description 39
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims description 95
- 108020004256 Beta-lactamase Proteins 0.000 claims description 72
- 230000000694 effects Effects 0.000 claims description 67
- 230000003115 biocidal effect Effects 0.000 claims description 62
- 230000035772 mutation Effects 0.000 claims description 57
- 239000003242 anti bacterial agent Substances 0.000 claims description 52
- 229940088710 antibiotic agent Drugs 0.000 claims description 48
- 239000003814 drug Substances 0.000 claims description 47
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 42
- 201000010099 disease Diseases 0.000 claims description 42
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 41
- 229960004755 ceftriaxone Drugs 0.000 claims description 40
- 229940024606 amino acid Drugs 0.000 claims description 39
- 235000001014 amino acid Nutrition 0.000 claims description 38
- 229930186147 Cephalosporin Natural products 0.000 claims description 36
- 229940124587 cephalosporin Drugs 0.000 claims description 36
- 150000001780 cephalosporins Chemical class 0.000 claims description 36
- 241000193163 Clostridioides difficile Species 0.000 claims description 32
- 229940124597 therapeutic agent Drugs 0.000 claims description 29
- 150000001413 amino acids Chemical group 0.000 claims description 27
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 24
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 23
- 235000004279 alanine Nutrition 0.000 claims description 23
- 230000001580 bacterial effect Effects 0.000 claims description 22
- 102200026652 rs28371717 Human genes 0.000 claims description 22
- -1 aliphatic amino acid Chemical class 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 21
- 210000000813 small intestine Anatomy 0.000 claims description 21
- 229930182555 Penicillin Natural products 0.000 claims description 20
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 18
- 102220581989 Putative uncharacterized protein FER1L6-AS1_S240D_mutation Human genes 0.000 claims description 18
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 18
- 125000001165 hydrophobic group Chemical group 0.000 claims description 18
- 230000002209 hydrophobic effect Effects 0.000 claims description 17
- 230000002411 adverse Effects 0.000 claims description 16
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 235000003704 aspartic acid Nutrition 0.000 claims description 16
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 16
- 230000012010 growth Effects 0.000 claims description 16
- 102200055882 rs121917721 Human genes 0.000 claims description 16
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 15
- 102000040430 polynucleotide Human genes 0.000 claims description 15
- 108091033319 polynucleotide Proteins 0.000 claims description 15
- 239000002157 polynucleotide Substances 0.000 claims description 15
- 229940049954 penicillin Drugs 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 210000001198 duodenum Anatomy 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 11
- 102000035195 Peptidases Human genes 0.000 claims description 11
- 108091005804 Peptidases Proteins 0.000 claims description 11
- 102220398968 c.731G>C Human genes 0.000 claims description 11
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 claims description 11
- 229960001139 cefazolin Drugs 0.000 claims description 11
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 claims description 11
- 229960004682 cefoperazone Drugs 0.000 claims description 11
- 239000004365 Protease Substances 0.000 claims description 10
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 239000004475 Arginine Substances 0.000 claims description 8
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 8
- 235000009582 asparagine Nutrition 0.000 claims description 8
- 229960001230 asparagine Drugs 0.000 claims description 8
- 239000003781 beta lactamase inhibitor Substances 0.000 claims description 8
- 229940126813 beta-lactamase inhibitor Drugs 0.000 claims description 8
- 230000003197 catalytic effect Effects 0.000 claims description 8
- 230000001419 dependent effect Effects 0.000 claims description 8
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 8
- 210000001630 jejunum Anatomy 0.000 claims description 8
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 7
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 7
- 239000004473 Threonine Substances 0.000 claims description 7
- 108010068385 carbapenemase Proteins 0.000 claims description 7
- 210000003405 ileum Anatomy 0.000 claims description 7
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
- 229960003324 clavulanic acid Drugs 0.000 claims description 6
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 6
- 244000005709 gut microbiome Species 0.000 claims description 6
- 102220096007 rs876660626 Human genes 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 210000001072 colon Anatomy 0.000 claims description 5
- 235000018417 cysteine Nutrition 0.000 claims description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
- 230000000593 degrading effect Effects 0.000 claims description 5
- 235000013922 glutamic acid Nutrition 0.000 claims description 5
- 239000004220 glutamic acid Substances 0.000 claims description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 5
- 229960000310 isoleucine Drugs 0.000 claims description 5
- 229930182817 methionine Natural products 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 229960005256 sulbactam Drugs 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 239000004474 valine Substances 0.000 claims description 5
- 208000004998 Abdominal Pain Diseases 0.000 claims description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 4
- 102220586070 Two pore channel protein 2_D276K_mutation Human genes 0.000 claims description 4
- 108010059993 Vancomycin Proteins 0.000 claims description 4
- 230000002159 abnormal effect Effects 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 102000020235 metallo-beta-lactamase Human genes 0.000 claims description 4
- 108060004734 metallo-beta-lactamase Proteins 0.000 claims description 4
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 4
- 230000036470 plasma concentration Effects 0.000 claims description 4
- 239000006041 probiotic Substances 0.000 claims description 4
- 230000000529 probiotic effect Effects 0.000 claims description 4
- 235000018291 probiotics Nutrition 0.000 claims description 4
- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 claims description 4
- 229960003865 tazobactam Drugs 0.000 claims description 4
- 229960003165 vancomycin Drugs 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- 206010011409 Cross infection Diseases 0.000 claims 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 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 108010034752 beta-lactamase NDM-1 Proteins 0.000 claims description 3
- 206010009887 colitis Diseases 0.000 claims description 3
- 230000002550 fecal effect Effects 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 229960000282 metronidazole Drugs 0.000 claims description 3
- 244000000010 microbial pathogen Species 0.000 claims description 3
- 229960003040 rifaximin Drugs 0.000 claims description 3
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 claims description 3
- 102200039244 rs121908530 Human genes 0.000 claims description 3
- 102200043150 rs121909589 Human genes 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- FKENQMMABCRJMK-LWOQYNTDSA-N (5r)-3,3-dimethyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=S1(=O)C(C)(C)C(C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-LWOQYNTDSA-N 0.000 claims description 2
- 101710196510 BRCA1-associated protein Proteins 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 101710144867 Inositol monophosphatase Proteins 0.000 claims description 2
- 108020005210 Integrons Proteins 0.000 claims description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 2
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 claims description 2
- 206010037128 Pseudomembranous colitis Diseases 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- 206010034674 peritonitis Diseases 0.000 claims description 2
- 102220493526 Sodium/calcium exchanger 3_F33Y_mutation Human genes 0.000 claims 4
- 108010071437 oxacillinase Proteins 0.000 claims 3
- 108010056874 AmpC beta-lactamases Proteins 0.000 claims 1
- 101100163160 Penicillium roqueforti AREA gene Proteins 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 abstract description 15
- PJYYBCXMCWDUAZ-JJJZTNILSA-N 2,3,14,20,22-pentahydroxy-(2β,3β,5β,22R)-Cholest-7-en-6-one Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 PJYYBCXMCWDUAZ-JJJZTNILSA-N 0.000 description 127
- 101800001318 Capsid protein VP4 Proteins 0.000 description 122
- 239000003795 chemical substances by application Substances 0.000 description 78
- 108090000623 proteins and genes Proteins 0.000 description 57
- 235000018102 proteins Nutrition 0.000 description 52
- 102000004169 proteins and genes Human genes 0.000 description 52
- 239000000523 sample Substances 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 39
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 31
- 229960000723 ampicillin Drugs 0.000 description 30
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 26
- 238000003556 assay Methods 0.000 description 25
- 241000282414 Homo sapiens Species 0.000 description 21
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 21
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 20
- 229960004261 cefotaxime Drugs 0.000 description 20
- 238000010828 elution Methods 0.000 description 19
- 239000008103 glucose Substances 0.000 description 19
- 101800001090 Protein 3A Proteins 0.000 description 17
- 241000588724 Escherichia coli Species 0.000 description 16
- 102220542936 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A_S233Y_mutation Human genes 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
- 229940079593 drug Drugs 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 235000002639 sodium chloride Nutrition 0.000 description 16
- 239000012530 fluid Substances 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 244000005700 microbiome Species 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- ORFOPKXBNMVMKC-DWVKKRMSSA-N ceftazidime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-N 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 210000002429 large intestine Anatomy 0.000 description 13
- 102220303093 rs141811441 Human genes 0.000 description 13
- 102200022214 rs372080941 Human genes 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 13
- 244000063299 Bacillus subtilis Species 0.000 description 12
- 235000014469 Bacillus subtilis Nutrition 0.000 description 12
- 102220509110 Sphingosine 1-phosphate receptor 1_E146Y_mutation Human genes 0.000 description 12
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 12
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 12
- 235000011130 ammonium sulphate Nutrition 0.000 description 12
- 229960000484 ceftazidime Drugs 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 229960001668 cefuroxime Drugs 0.000 description 11
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 239000013598 vector Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 125000003275 alpha amino acid group Chemical group 0.000 description 10
- 238000000576 coating method Methods 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 102220520039 Guanylyl cyclase-activating protein 1_E128Y_mutation Human genes 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 9
- 229960002100 cefepime Drugs 0.000 description 9
- HVFLCNVBZFFHBT-ZKDACBOMSA-N cefepime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 HVFLCNVBZFFHBT-ZKDACBOMSA-N 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 230000003111 delayed effect Effects 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 230000000968 intestinal effect Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000002741 site-directed mutagenesis Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 102220645900 Protein pitchfork_T48R_mutation Human genes 0.000 description 8
- 102220543096 Protein pitchfork_T48V_mutation Human genes 0.000 description 8
- 238000013270 controlled release Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 7
- 229940043312 ampicillin / sulbactam Drugs 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000012228 culture supernatant Substances 0.000 description 7
- NWOYIVRVSJDTLK-YSDBFZIDSA-L disodium;(2s,5r,6r)-6-[[(2r)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;(1r,4s)-3,3-dimethyl-2,2,6-trioxo-2$l^{6}-thiabicyclo[3.2.0]heptane-4-carboxylate Chemical compound [Na+].[Na+].O=S1(=O)C(C)(C)[C@H](C([O-])=O)C2C(=O)C[C@H]21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 NWOYIVRVSJDTLK-YSDBFZIDSA-L 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 235000011187 glycerol Nutrition 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 210000000936 intestine Anatomy 0.000 description 7
- 229960002260 meropenem Drugs 0.000 description 7
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 238000002708 random mutagenesis Methods 0.000 description 7
- 238000013268 sustained release Methods 0.000 description 7
- 239000012730 sustained-release form Substances 0.000 description 7
- JFPVXVDWJQMJEE-QMTHXVAHSA-N Cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)C(=NOC)C1=CC=CO1 JFPVXVDWJQMJEE-QMTHXVAHSA-N 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 101710084578 Short neurotoxin 1 Proteins 0.000 description 6
- 101710182532 Toxin a Proteins 0.000 description 6
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
- 210000004534 cecum Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 210000001731 descending colon Anatomy 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 101150019841 penP gene Proteins 0.000 description 6
- 150000002960 penicillins Chemical class 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 150000003952 β-lactams Chemical class 0.000 description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 5
- 102220590671 Adenylosuccinate synthetase isozyme 1_N106Y_mutation Human genes 0.000 description 5
- 102220506476 Phenylalanine-tRNA ligase, mitochondrial_P77V_mutation Human genes 0.000 description 5
- 102220472148 Protein ENL_E11N_mutation Human genes 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 210000001815 ascending colon Anatomy 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 238000012807 shake-flask culturing Methods 0.000 description 5
- 210000001599 sigmoid colon Anatomy 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 210000003384 transverse colon Anatomy 0.000 description 5
- LHNIIDJCEODSHA-OQRUQETBSA-N (6r,7r)-3-[(e)-2-(2,4-dinitrophenyl)ethenyl]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)O)\C=C\C=1C(=CC(=CC=1)[N+]([O-])=O)[N+]([O-])=O)C(=O)CC1=CC=CS1 LHNIIDJCEODSHA-OQRUQETBSA-N 0.000 description 4
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 4
- 108010011667 Ala-Phe-Ala Proteins 0.000 description 4
- 102220638160 Arylamine N-acetyltransferase 1_R64K_mutation Human genes 0.000 description 4
- 102220487212 Cytochrome b-245 chaperone 1_D188H_mutation Human genes 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- 102220597499 Formyltetrahydrofolate synthetase_K56T_mutation Human genes 0.000 description 4
- 102220576557 HLA class I histocompatibility antigen, A alpha chain_F33Y_mutation Human genes 0.000 description 4
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 4
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 108010087702 Penicillinase Proteins 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000009098 adjuvant therapy Methods 0.000 description 4
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 4
- 108010032601 beta-lactamase CTX-2 Proteins 0.000 description 4
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 4
- 108010034529 leucyl-lysine Proteins 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 229940124531 pharmaceutical excipient Drugs 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229960002292 piperacillin Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 210000001236 prokaryotic cell Anatomy 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000000547 structure data Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102220580808 15-hydroxyprostaglandin dehydrogenase [NAD(+)]_Q148N_mutation Human genes 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
- 102220590672 Adenylosuccinate synthetase isozyme 1_N106S_mutation Human genes 0.000 description 3
- 102220477559 Aldehyde oxidase_E175H_mutation Human genes 0.000 description 3
- XRNXPIGJPQHCPC-RCWTZXSCSA-N Arg-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)C(O)=O XRNXPIGJPQHCPC-RCWTZXSCSA-N 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102220554117 Cyclic GMP-AMP synthase_L17T_mutation Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102220597459 Formyltetrahydrofolate synthetase_K56Q_mutation Human genes 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 102220561149 Furin_E249Q_mutation Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 231100000111 LD50 Toxicity 0.000 description 3
- 240000001046 Lactobacillus acidophilus Species 0.000 description 3
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102220514706 Myoglobin_D94S_mutation Human genes 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 102220512045 Protein N-terminal glutamine amidohydrolase_E121D_mutation Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000235070 Saccharomyces Species 0.000 description 3
- 102220478924 Sodium channel protein type 2 subunit alpha_A240S_mutation Human genes 0.000 description 3
- 102220509095 Sphingosine 1-phosphate receptor 1_E146T_mutation Human genes 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 102220529137 T-box transcription factor TBX19_P226W_mutation Human genes 0.000 description 3
- 101710182223 Toxin B Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229960003022 amoxicillin Drugs 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000000941 bile Anatomy 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229960000603 cefalotin Drugs 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 230000002906 microbiologic effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 3
- 229950009506 penicillinase Drugs 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011533 pre-incubation Methods 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 239000013074 reference sample Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- LSLIRHLIUDVNBN-CIUDSAMLSA-N Ala-Asp-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN LSLIRHLIUDVNBN-CIUDSAMLSA-N 0.000 description 2
- CSAHOYQKNHGDHX-ACZMJKKPSA-N Ala-Gln-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CSAHOYQKNHGDHX-ACZMJKKPSA-N 0.000 description 2
- SMCGQGDVTPFXKB-XPUUQOCRSA-N Ala-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N SMCGQGDVTPFXKB-XPUUQOCRSA-N 0.000 description 2
- CFPQUJZTLUQUTJ-HTFCKZLJSA-N Ala-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)N CFPQUJZTLUQUTJ-HTFCKZLJSA-N 0.000 description 2
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 2
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 2
- KQESEZXHYOUIIM-CQDKDKBSSA-N Ala-Lys-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KQESEZXHYOUIIM-CQDKDKBSSA-N 0.000 description 2
- XRUJOVRWNMBAAA-NHCYSSNCSA-N Ala-Phe-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 XRUJOVRWNMBAAA-NHCYSSNCSA-N 0.000 description 2
- SYIFFFHSXBNPMC-UWJYBYFXSA-N Ala-Ser-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N SYIFFFHSXBNPMC-UWJYBYFXSA-N 0.000 description 2
- MTDDMSUUXNQMKK-BPNCWPANSA-N Ala-Tyr-Arg Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N MTDDMSUUXNQMKK-BPNCWPANSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 102220625509 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3_L177N_mutation Human genes 0.000 description 2
- 102220625508 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3_L177Q_mutation Human genes 0.000 description 2
- 102220566105 Antileukoproteinase_L97R_mutation Human genes 0.000 description 2
- ZTKHZAXGTFXUDD-VEVYYDQMSA-N Arg-Asn-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZTKHZAXGTFXUDD-VEVYYDQMSA-N 0.000 description 2
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 2
- HJDNZFIYILEIKR-OSUNSFLBSA-N Arg-Ile-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HJDNZFIYILEIKR-OSUNSFLBSA-N 0.000 description 2
- CZUHPNLXLWMYMG-UBHSHLNASA-N Arg-Phe-Ala Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 CZUHPNLXLWMYMG-UBHSHLNASA-N 0.000 description 2
- DPLFNLDACGGBAK-KKUMJFAQSA-N Arg-Phe-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N DPLFNLDACGGBAK-KKUMJFAQSA-N 0.000 description 2
- QHUOOCKNNURZSL-IHRRRGAJSA-N Arg-Tyr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O QHUOOCKNNURZSL-IHRRRGAJSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZWASIOHRQWRWAS-UGYAYLCHSA-N Asn-Asp-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZWASIOHRQWRWAS-UGYAYLCHSA-N 0.000 description 2
- DMLSCRJBWUEALP-LAEOZQHASA-N Asn-Glu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O DMLSCRJBWUEALP-LAEOZQHASA-N 0.000 description 2
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 2
- YUOXLJYVSZYPBJ-CIUDSAMLSA-N Asn-Pro-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O YUOXLJYVSZYPBJ-CIUDSAMLSA-N 0.000 description 2
- GKKUBLFXKRDMFC-BQBZGAKWSA-N Asn-Pro-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O GKKUBLFXKRDMFC-BQBZGAKWSA-N 0.000 description 2
- NJSNXIOKBHPFMB-GMOBBJLQSA-N Asn-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)N)N NJSNXIOKBHPFMB-GMOBBJLQSA-N 0.000 description 2
- NJIKKGUVGUBICV-ZLUOBGJFSA-N Asp-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O NJIKKGUVGUBICV-ZLUOBGJFSA-N 0.000 description 2
- YNQIDCRRTWGHJD-ZLUOBGJFSA-N Asp-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(O)=O YNQIDCRRTWGHJD-ZLUOBGJFSA-N 0.000 description 2
- SBHUBSDEZQFJHJ-CIUDSAMLSA-N Asp-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O SBHUBSDEZQFJHJ-CIUDSAMLSA-N 0.000 description 2
- CELPEWWLSXMVPH-CIUDSAMLSA-N Asp-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O CELPEWWLSXMVPH-CIUDSAMLSA-N 0.000 description 2
- GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 description 2
- 102220617592 B1 bradykinin receptor_S42C_mutation Human genes 0.000 description 2
- 102220470698 BUD13 homolog_V30P_mutation Human genes 0.000 description 2
- 102220534033 Cadherin-1_P170V_mutation Human genes 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 102220472972 Cytochrome c oxidase subunit 6B1_E141V_mutation Human genes 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 208000005156 Dehydration Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 102220476614 Dynein axonemal assembly factor 10_T185S_mutation Human genes 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 2
- 102220563892 Forkhead box protein O3_K245A_mutation Human genes 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102220541665 Gliomedin_L156C_mutation Human genes 0.000 description 2
- ZEEPYMXTJWIMSN-GUBZILKMSA-N Gln-Lys-Ser Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ZEEPYMXTJWIMSN-GUBZILKMSA-N 0.000 description 2
- FYBSCGZLICNOBA-XQXXSGGOSA-N Glu-Ala-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FYBSCGZLICNOBA-XQXXSGGOSA-N 0.000 description 2
- HVYWQYLBVXMXSV-GUBZILKMSA-N Glu-Leu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HVYWQYLBVXMXSV-GUBZILKMSA-N 0.000 description 2
- IDEODOAVGCMUQV-GUBZILKMSA-N Glu-Ser-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IDEODOAVGCMUQV-GUBZILKMSA-N 0.000 description 2
- MWTGQXBHVRTCOR-GLLZPBPUSA-N Glu-Thr-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MWTGQXBHVRTCOR-GLLZPBPUSA-N 0.000 description 2
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 2
- 102220529427 Glutathione S-transferase LANCL1_R134N_mutation Human genes 0.000 description 2
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 2
- YXTFLTJYLIAZQG-FJXKBIBVSA-N Gly-Thr-Arg Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YXTFLTJYLIAZQG-FJXKBIBVSA-N 0.000 description 2
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 2
- KDDKJKKQODQQBR-NHCYSSNCSA-N His-Val-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N KDDKJKKQODQQBR-NHCYSSNCSA-N 0.000 description 2
- TZCGZYWNIDZZMR-UHFFFAOYSA-N Ile-Arg-Ala Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(C)C(O)=O)CCCN=C(N)N TZCGZYWNIDZZMR-UHFFFAOYSA-N 0.000 description 2
- KIMHKBDJQQYLHU-PEFMBERDSA-N Ile-Glu-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KIMHKBDJQQYLHU-PEFMBERDSA-N 0.000 description 2
- KFVUBLZRFSVDGO-BYULHYEWSA-N Ile-Gly-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O KFVUBLZRFSVDGO-BYULHYEWSA-N 0.000 description 2
- 102220624327 Interferon alpha-8_N106Y_mutation Human genes 0.000 description 2
- 102220471661 Interleukin-10 receptor subunit alpha_W220F_mutation Human genes 0.000 description 2
- 244000199866 Lactobacillus casei Species 0.000 description 2
- 235000013958 Lactobacillus casei Nutrition 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 2
- RFUBXQQFJFGJFV-GUBZILKMSA-N Leu-Asn-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RFUBXQQFJFGJFV-GUBZILKMSA-N 0.000 description 2
- RIMMMMYKGIBOSN-DCAQKATOSA-N Leu-Asn-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O RIMMMMYKGIBOSN-DCAQKATOSA-N 0.000 description 2
- CLVUXCBGKUECIT-HJGDQZAQSA-N Leu-Asp-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CLVUXCBGKUECIT-HJGDQZAQSA-N 0.000 description 2
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 2
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 2
- DBSLVQBXKVKDKJ-BJDJZHNGSA-N Leu-Ile-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DBSLVQBXKVKDKJ-BJDJZHNGSA-N 0.000 description 2
- AVEGDIAXTDVBJS-XUXIUFHCSA-N Leu-Ile-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AVEGDIAXTDVBJS-XUXIUFHCSA-N 0.000 description 2
- KOSWSHVQIVTVQF-ZPFDUUQYSA-N Leu-Ile-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KOSWSHVQIVTVQF-ZPFDUUQYSA-N 0.000 description 2
- KUIDCYNIEJBZBU-AJNGGQMLSA-N Leu-Ile-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O KUIDCYNIEJBZBU-AJNGGQMLSA-N 0.000 description 2
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 2
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 2
- YVMQJGWLHRWMDF-MNXVOIDGSA-N Lys-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N YVMQJGWLHRWMDF-MNXVOIDGSA-N 0.000 description 2
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 2
- YPLVCBKEPJPBDQ-MELADBBJSA-N Lys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N YPLVCBKEPJPBDQ-MELADBBJSA-N 0.000 description 2
- ALGGDNMLQNFVIZ-SRVKXCTJSA-N Lys-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N ALGGDNMLQNFVIZ-SRVKXCTJSA-N 0.000 description 2
- UQRZFMQQXXJTTF-AVGNSLFASA-N Lys-Lys-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O UQRZFMQQXXJTTF-AVGNSLFASA-N 0.000 description 2
- IKXQOBUBZSOWDY-AVGNSLFASA-N Lys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N IKXQOBUBZSOWDY-AVGNSLFASA-N 0.000 description 2
- 102220514509 Membrane-bound transcription factor site-2 protease_E172Q_mutation Human genes 0.000 description 2
- UNPGTBHYKJOCCZ-DCAQKATOSA-N Met-Lys-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O UNPGTBHYKJOCCZ-DCAQKATOSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 102220561253 Myocardin-related transcription factor B_L52D_mutation Human genes 0.000 description 2
- 102220561257 Myocardin-related transcription factor B_L89D_mutation Human genes 0.000 description 2
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 2
- 102220531926 N-acetylaspartylglutamate synthase A_L109M_mutation Human genes 0.000 description 2
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 2
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 2
- 102220581723 Neuron navigator 1_D127W_mutation Human genes 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 102220547894 Nucleobindin-1_N140H_mutation Human genes 0.000 description 2
- 208000012868 Overgrowth Diseases 0.000 description 2
- UHRNIXJAGGLKHP-DLOVCJGASA-N Phe-Ala-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O UHRNIXJAGGLKHP-DLOVCJGASA-N 0.000 description 2
- 102220517306 Phosphate-regulating neutral endopeptidase PHEX_K168R_mutation Human genes 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 102220596269 Pre-mRNA-splicing factor CWC22 homolog_G211W_mutation Human genes 0.000 description 2
- VJLJGKQAOQJXJG-CIUDSAMLSA-N Pro-Asp-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VJLJGKQAOQJXJG-CIUDSAMLSA-N 0.000 description 2
- SGCZFWSQERRKBD-BQBZGAKWSA-N Pro-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 SGCZFWSQERRKBD-BQBZGAKWSA-N 0.000 description 2
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 2
- FHJQROWZEJFZPO-SRVKXCTJSA-N Pro-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FHJQROWZEJFZPO-SRVKXCTJSA-N 0.000 description 2
- 102220511117 Probable aminopeptidase NPEPL1_G86P_mutation Human genes 0.000 description 2
- 102220506594 Prolyl endopeptidase FAP_R123E_mutation Human genes 0.000 description 2
- 102220627977 Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2_N106T_mutation Human genes 0.000 description 2
- 102220620624 Protein pitchfork_D179A_mutation Human genes 0.000 description 2
- 102220645899 Protein pitchfork_T48W_mutation Human genes 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 241001472782 Proteus penneri Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102220536030 Quinone oxidoreductase-like protein 1_N143L_mutation Human genes 0.000 description 2
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 2
- QKQDTEYDEIJPNK-GUBZILKMSA-N Ser-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO QKQDTEYDEIJPNK-GUBZILKMSA-N 0.000 description 2
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- MQCPGOZXFSYJPS-KZVJFYERSA-N Thr-Ala-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MQCPGOZXFSYJPS-KZVJFYERSA-N 0.000 description 2
- HJOSVGCWOTYJFG-WDCWCFNPSA-N Thr-Glu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N)O HJOSVGCWOTYJFG-WDCWCFNPSA-N 0.000 description 2
- SLUWOCTZVGMURC-BFHQHQDPSA-N Thr-Gly-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O SLUWOCTZVGMURC-BFHQHQDPSA-N 0.000 description 2
- NIEWSKWFURSECR-FOHZUACHSA-N Thr-Gly-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O NIEWSKWFURSECR-FOHZUACHSA-N 0.000 description 2
- UBDDORVPVLEECX-FJXKBIBVSA-N Thr-Gly-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O UBDDORVPVLEECX-FJXKBIBVSA-N 0.000 description 2
- AHOLTQCAVBSUDP-PPCPHDFISA-N Thr-Ile-Lys Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O AHOLTQCAVBSUDP-PPCPHDFISA-N 0.000 description 2
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 2
- DVWAIHZOPSYMSJ-ZVZYQTTQSA-N Trp-Glu-Val Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O)=CNC2=C1 DVWAIHZOPSYMSJ-ZVZYQTTQSA-N 0.000 description 2
- FBGDDUKYOBNZJL-WDSOQIARSA-N Trp-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N FBGDDUKYOBNZJL-WDSOQIARSA-N 0.000 description 2
- QUIXRGCMQOXUSV-SZMVWBNQSA-N Trp-Pro-Pro Chemical compound O=C([C@@H]1CCCN1C(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)N1CCC[C@H]1C(O)=O QUIXRGCMQOXUSV-SZMVWBNQSA-N 0.000 description 2
- ITDWWLTTWRRLCC-KJEVXHAQSA-N Tyr-Thr-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ITDWWLTTWRRLCC-KJEVXHAQSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- IQQYYFPCWKWUHW-YDHLFZDLSA-N Val-Asn-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N IQQYYFPCWKWUHW-YDHLFZDLSA-N 0.000 description 2
- XXROXFHCMVXETG-UWVGGRQHSA-N Val-Gly-Val Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXROXFHCMVXETG-UWVGGRQHSA-N 0.000 description 2
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 102220634406 Vitamin K epoxide reductase complex subunit 1_R98E_mutation Human genes 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 102220507794 Xaa-Pro dipeptidase_E200Q_mutation Human genes 0.000 description 2
- 241000490645 Yarrowia sp. Species 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 108010005233 alanylglutamic acid Proteins 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 108010038633 aspartylglutamate Proteins 0.000 description 2
- 108010092854 aspartyllysine Proteins 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 229940000635 beta-alanine Drugs 0.000 description 2
- 238000003766 bioinformatics method Methods 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 210000004913 chyme Anatomy 0.000 description 2
- QJHCNBWLPSXHBL-UHFFFAOYSA-N cimetidine hydrochloride Chemical compound [H+].[Cl-].N#C/N=C(/NC)NCCSCC=1N=CNC=1C QJHCNBWLPSXHBL-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 239000012468 concentrated sample 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
- 239000007857 degradation product Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- KWORUUGOSLYAGD-YPPDDXJESA-N esomeprazole magnesium Chemical compound [Mg+2].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-YPPDDXJESA-N 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 2
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 208000024798 heartburn Diseases 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000004679 hydroxides Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 229940017800 lactobacillus casei Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 229960003085 meticillin Drugs 0.000 description 2
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- GPXLMGHLHQJAGZ-JTDSTZFVSA-N nafcillin Chemical compound C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C(O)=O)=O)C(OCC)=CC=C21 GPXLMGHLHQJAGZ-JTDSTZFVSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229940112641 nexium Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000002974 pharmacogenomic effect Effects 0.000 description 2
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229940032668 prevacid Drugs 0.000 description 2
- 229940089505 prilosec Drugs 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000000941 radioactive substance Substances 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 229940106721 tagamet Drugs 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- BVCKFLJARNKCSS-DWPRYXJFSA-N temocillin Chemical compound N([C@]1(OC)C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C(O)=O)C=1C=CSC=1 BVCKFLJARNKCSS-DWPRYXJFSA-N 0.000 description 2
- 108010061238 threonyl-glycine Proteins 0.000 description 2
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- HJHSDOOIPJGRSK-QMMMGPOBSA-N (2s)-2-(hexylamino)propanoic acid Chemical class CCCCCCN[C@@H](C)C(O)=O HJHSDOOIPJGRSK-QMMMGPOBSA-N 0.000 description 1
- MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 1
- NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 1
- LITBAYYWXZOHAW-XDZRHBBOSA-N (2s,5r,6r)-6-[[(2r)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2s,3s,5r)-3-methyl-4,4,7-trioxo-3-(triazol-1-ylmethyl)-4$l^{6}-thia-1-azabicyclo[3.2.0]hept Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1.O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 LITBAYYWXZOHAW-XDZRHBBOSA-N 0.000 description 1
- QJVHTELASVOWBE-AGNWQMPPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 QJVHTELASVOWBE-AGNWQMPPSA-N 0.000 description 1
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-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
- CVHZOJJKTDOEJC-UHFFFAOYSA-M 1,1-dioxo-1,2-benzothiazol-3-olate Chemical compound C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-M 0.000 description 1
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical group OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 1
- 102220580811 15-hydroxyprostaglandin dehydrogenase [NAD(+)]_Q148A_mutation Human genes 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- 102220500361 2-acylglycerol O-acyltransferase 2_P196H_mutation Human genes 0.000 description 1
- WROUWQQRXUBECT-UHFFFAOYSA-N 2-ethylacrylic acid Chemical compound CCC(=C)C(O)=O WROUWQQRXUBECT-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
- HMGCGUWFPZVPEK-UHFFFAOYSA-N 2-naphthalen-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=C1 HMGCGUWFPZVPEK-UHFFFAOYSA-N 0.000 description 1
- 102220624198 3-hydroxy-3-methylglutaryl-coenzyme A reductase_Y75A_mutation Human genes 0.000 description 1
- GUPXYSSGJWIURR-UHFFFAOYSA-N 3-octoxypropane-1,2-diol Chemical compound CCCCCCCCOCC(O)CO GUPXYSSGJWIURR-UHFFFAOYSA-N 0.000 description 1
- 102220589097 39S ribosomal protein L1, mitochondrial_K238S_mutation Human genes 0.000 description 1
- 102220532102 39S ribosomal protein L4, mitochondrial_S100A_mutation Human genes 0.000 description 1
- 102220643913 39S ribosomal protein L9, mitochondrial_D101E_mutation Human genes 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- 102220575769 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9_N62Q_mutation Human genes 0.000 description 1
- 102220487774 4-hydroxybenzoate polyprenyltransferase, mitochondrial_D71E_mutation Human genes 0.000 description 1
- 102220490664 4-hydroxybenzoate polyprenyltransferase, mitochondrial_K182F_mutation Human genes 0.000 description 1
- 102220487767 4-hydroxybenzoate polyprenyltransferase, mitochondrial_S234K_mutation Human genes 0.000 description 1
- 102220487776 4-hydroxybenzoate polyprenyltransferase, mitochondrial_S57T_mutation Human genes 0.000 description 1
- 102220587605 4-hydroxybenzoate polyprenyltransferase, mitochondrial_S96N_mutation Human genes 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 102220575569 40S ribosomal protein S16_K56D_mutation Human genes 0.000 description 1
- 102220561532 5'-AMP-activated protein kinase subunit gamma-1_K3I_mutation Human genes 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- GEHRSERUQRFUFW-UHFFFAOYSA-N 5-ethylhex-2-ynedioic acid Chemical compound CCC(C(O)=O)CC#CC(O)=O GEHRSERUQRFUFW-UHFFFAOYSA-N 0.000 description 1
- 102220598666 5-hydroxytryptamine receptor 1E_R33E_mutation Human genes 0.000 description 1
- 102220497104 5-hydroxytryptamine receptor 3B_E59L_mutation Human genes 0.000 description 1
- 102220497101 5-hydroxytryptamine receptor 3B_E59Q_mutation Human genes 0.000 description 1
- 102220470040 60S acidic ribosomal protein P0-like_L47H_mutation Human genes 0.000 description 1
- 102220588949 60S ribosomal protein L7-like 1_Q63A_mutation Human genes 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- 102220535257 A disintegrin and metalloproteinase with thrombospondin motifs 9_S96T_mutation Human genes 0.000 description 1
- 102220530504 ADAMTS-like protein 2_R69F_mutation Human genes 0.000 description 1
- 102220546915 ADP-ribosylation factor 3_D35L_mutation Human genes 0.000 description 1
- 102220491140 ADP-ribosylation factor-like protein 14_L232G_mutation Human genes 0.000 description 1
- 102220631993 AH receptor-interacting protein_K120R_mutation Human genes 0.000 description 1
- 102220609864 AP-1 complex subunit sigma-1A_L139H_mutation Human genes 0.000 description 1
- 102220553765 APC membrane recruitment protein 1_E116A_mutation Human genes 0.000 description 1
- 102220511219 APC membrane recruitment protein 1_F6I_mutation Human genes 0.000 description 1
- 102220511160 APC membrane recruitment protein 1_G86S_mutation Human genes 0.000 description 1
- 102220554127 APC membrane recruitment protein 1_K45A_mutation Human genes 0.000 description 1
- 102220554146 APC membrane recruitment protein 1_L107A_mutation Human genes 0.000 description 1
- 102220570560 ATP-binding cassette sub-family C member 4_G187W_mutation Human genes 0.000 description 1
- 102220549849 ATP-binding cassette sub-family D member 1_A95D_mutation Human genes 0.000 description 1
- 102220552290 ATP-binding cassette sub-family D member 1_N214D_mutation Human genes 0.000 description 1
- 102220638472 ATP-binding cassette sub-family G member 1_K124M_mutation Human genes 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000589220 Acetobacter Species 0.000 description 1
- 102220478419 Acetyl-coenzyme A thioesterase_L190H_mutation Human genes 0.000 description 1
- 102220491522 Acid ceramidase_E138V_mutation Human genes 0.000 description 1
- 102220490015 Acid ceramidase_N259Q_mutation Human genes 0.000 description 1
- 102220566256 Acid-sensing ion channel 3_Y67N_mutation Human genes 0.000 description 1
- 102220565734 Acid-sensing ion channel 4_T26K_mutation Human genes 0.000 description 1
- 102220579947 Acidic mammalian chitinase_D167E_mutation Human genes 0.000 description 1
- 241001019659 Acremonium <Plectosphaerellaceae> Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 102220646192 Actin-like protein 7A_A31Y_mutation Human genes 0.000 description 1
- 102220560785 Acyl-CoA dehydrogenase family member 10_D71Y_mutation Human genes 0.000 description 1
- 102220466236 Acyl-coenzyme A thioesterase MBLAC2_K119A_mutation Human genes 0.000 description 1
- 102220466237 Acyl-coenzyme A thioesterase MBLAC2_K168A_mutation Human genes 0.000 description 1
- 102220511881 Acyl-coenzyme A thioesterase THEM4_L17R_mutation Human genes 0.000 description 1
- 102220511405 Adenine DNA glycosylase_V231M_mutation Human genes 0.000 description 1
- 102220466742 Adenosine 5'-monophosphoramidase HINT1_I44W_mutation Human genes 0.000 description 1
- 102220573865 Adenosine receptor A2a_V83D_mutation Human genes 0.000 description 1
- 102220636430 Adiponectin receptor protein 1_G113W_mutation Human genes 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- MMLHRUJLOUSRJX-CIUDSAMLSA-N Ala-Ser-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN MMLHRUJLOUSRJX-CIUDSAMLSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102220469546 Aldo-keto reductase family 1 member C2_K238D_mutation Human genes 0.000 description 1
- 102220495836 Alkaline ceramidase 1_G25T_mutation Human genes 0.000 description 1
- 102220488924 Alkaline phosphatase, tissue-nonspecific isozyme_I218S_mutation Human genes 0.000 description 1
- 102220546985 Alpha-1B adrenergic receptor_V51G_mutation Human genes 0.000 description 1
- 102220478243 Alpha-endosulfine_E36G_mutation Human genes 0.000 description 1
- 102220486650 Alpha-galactosidase A_A230T_mutation Human genes 0.000 description 1
- 102220486668 Alpha-galactosidase A_D244H_mutation Human genes 0.000 description 1
- 102220486421 Alpha-galactosidase A_I219N_mutation Human genes 0.000 description 1
- 102220486488 Alpha-galactosidase A_V254A_mutation Human genes 0.000 description 1
- 102220625507 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3_L177I_mutation Human genes 0.000 description 1
- 102220625513 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3_L177M_mutation Human genes 0.000 description 1
- 102220512138 Alpha-sarcoglycan_A93V_mutation Human genes 0.000 description 1
- 102220534069 Angiopoietin-related protein 3_R235T_mutation Human genes 0.000 description 1
- 102220613803 Angiotensin-converting enzyme 2_F40D_mutation Human genes 0.000 description 1
- 102220613706 Angiotensin-converting enzyme 2_R192D_mutation Human genes 0.000 description 1
- 102220493872 Ankyrin repeat and protein kinase domain-containing protein 1_D4Y_mutation Human genes 0.000 description 1
- 102220566102 Antileukoproteinase_L97G_mutation Human genes 0.000 description 1
- 102220472674 Antithrombin-III_I218N_mutation Human genes 0.000 description 1
- 102220615687 Apolipoprotein E_R154C_mutation Human genes 0.000 description 1
- 102220552601 Appetite-regulating hormone_L72M_mutation Human genes 0.000 description 1
- 241000219195 Arabidopsis thaliana Species 0.000 description 1
- 102220477812 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 11_G206I_mutation Human genes 0.000 description 1
- 102220482668 Arginine-hydroxylase NDUFAF5, mitochondrial_G86V_mutation Human genes 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- 102220535442 Aryl hydrocarbon receptor nuclear translocator-like protein 2_L122E_mutation Human genes 0.000 description 1
- 102220471100 Aryl hydrocarbon receptor_L118D_mutation Human genes 0.000 description 1
- 102220607129 Arylsulfatase A_G86D_mutation Human genes 0.000 description 1
- SVFOIXMRMLROHO-SRVKXCTJSA-N Asp-Asp-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SVFOIXMRMLROHO-SRVKXCTJSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102220478438 Atypical chemokine receptor 3_T147V_mutation Human genes 0.000 description 1
- 102220584075 Atypical kinase COQ8A, mitochondrial_A230I_mutation Human genes 0.000 description 1
- 102220584080 Atypical kinase COQ8A, mitochondrial_L229A_mutation Human genes 0.000 description 1
- 102220528623 Aurora kinase A_G198N_mutation Human genes 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 241000589151 Azotobacter Species 0.000 description 1
- 101150076489 B gene Proteins 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 102220617586 B1 bradykinin receptor_K16Q_mutation Human genes 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 102220567604 BICD family-like cargo adapter 2_T29S_mutation Human genes 0.000 description 1
- 102220603717 BPI fold-containing family A member 1_V253C_mutation Human genes 0.000 description 1
- 102220519450 BTB/POZ domain-containing protein KCTD1_L107W_mutation Human genes 0.000 description 1
- 241000193744 Bacillus amyloliquefaciens Species 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 101000695691 Bacillus licheniformis Beta-lactamase Proteins 0.000 description 1
- 101100004567 Bacillus licheniformis penP gene Proteins 0.000 description 1
- 102220518579 Baculoviral IAP repeat-containing protein 6_T43E_mutation Human genes 0.000 description 1
- 102220520233 Barrier-to-autointegration factor_G25Q_mutation Human genes 0.000 description 1
- 102220520198 Barrier-to-autointegration factor_R37E_mutation Human genes 0.000 description 1
- 102220521251 Bcl-2-associated transcription factor 1_S209C_mutation Human genes 0.000 description 1
- 102220521229 Beclin-2_A217L_mutation Human genes 0.000 description 1
- 102220618653 Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe_D70A_mutation Human genes 0.000 description 1
- 102220556603 Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase_G126F_mutation Human genes 0.000 description 1
- 102220623782 Beta-1,3-galactosyltransferase 6_S159Y_mutation Human genes 0.000 description 1
- 102220537158 Beta-nerve growth factor_G194C_mutation Human genes 0.000 description 1
- 102100021257 Beta-secretase 1 Human genes 0.000 description 1
- 101710150192 Beta-secretase 1 Proteins 0.000 description 1
- 102220628832 Beta-secretase 1_Y75F_mutation Human genes 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241001608472 Bifidobacterium longum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241001465180 Botrytis Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 102220486838 Breast cancer type 1 susceptibility protein_L165P_mutation Human genes 0.000 description 1
- 241000100312 Brettanomyces sp. Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 102220615754 C-C chemokine receptor type 5_L122P_mutation Human genes 0.000 description 1
- 102220485312 C-type lectin domain family 4 member E_R183V_mutation Human genes 0.000 description 1
- 102220549297 CBY1-interacting BAR domain-containing protein 1_A193S_mutation Human genes 0.000 description 1
- 102220548303 CBY1-interacting BAR domain-containing protein 1_G113A_mutation Human genes 0.000 description 1
- 102220548456 CBY1-interacting BAR domain-containing protein 1_G113S_mutation Human genes 0.000 description 1
- 102220548287 CBY1-interacting BAR domain-containing protein 1_G114P_mutation Human genes 0.000 description 1
- 102220549213 CBY1-interacting BAR domain-containing protein 1_K267A_mutation Human genes 0.000 description 1
- 102220549207 CBY1-interacting BAR domain-containing protein 1_R134A_mutation Human genes 0.000 description 1
- 102220549208 CBY1-interacting BAR domain-containing protein 1_R134E_mutation Human genes 0.000 description 1
- 102220616637 CCAAT/enhancer-binding protein alpha_E59A_mutation Human genes 0.000 description 1
- 102220616904 CCAAT/enhancer-binding protein alpha_Y67F_mutation Human genes 0.000 description 1
- 102220520339 CYFIP-related Rac1 interactor B_R161D_mutation Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102220602990 Calcium-binding mitochondrial carrier protein Aralar2_L232I_mutation Human genes 0.000 description 1
- 102220531161 Calcium/calmodulin-dependent protein kinase type II subunit delta_D236R_mutation Human genes 0.000 description 1
- 102220612213 Calcyclin-binding protein_E1D_mutation Human genes 0.000 description 1
- 102220614565 Calmodulin-3_G18A_mutation Human genes 0.000 description 1
- 102220614550 Calmodulin-3_G25A_mutation Human genes 0.000 description 1
- 102220614782 Calmodulin-3_K8A_mutation Human genes 0.000 description 1
- 102220614558 Calmodulin-3_N27A_mutation Human genes 0.000 description 1
- 102220614544 Calmodulin-3_R33A_mutation Human genes 0.000 description 1
- 102220590097 Calsyntenin-3_S209G_mutation Human genes 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 102220534036 Carbonic anhydrase 1_E172P_mutation Human genes 0.000 description 1
- 102220499814 Carbonic anhydrase 2_N62A_mutation Human genes 0.000 description 1
- 102220499813 Carbonic anhydrase 2_N62D_mutation Human genes 0.000 description 1
- 102220499807 Carbonic anhydrase 2_N62H_mutation Human genes 0.000 description 1
- 102220499804 Carbonic anhydrase 2_N62L_mutation Human genes 0.000 description 1
- 102220499805 Carbonic anhydrase 2_N62T_mutation Human genes 0.000 description 1
- 102220499800 Carbonic anhydrase 2_N62V_mutation Human genes 0.000 description 1
- 102220499436 Carbonic anhydrase 2_V142G_mutation Human genes 0.000 description 1
- 102220499441 Carbonic anhydrase 2_V142H_mutation Human genes 0.000 description 1
- 102220499448 Carbonic anhydrase 2_V142Y_mutation Human genes 0.000 description 1
- 102220485544 Carboxypeptidase A4_R183L_mutation Human genes 0.000 description 1
- 102220547739 Carcinoembryonic antigen-related cell adhesion molecule 3_K90Q_mutation Human genes 0.000 description 1
- 102220547700 Carcinoembryonic antigen-related cell adhesion molecule 3_N74G_mutation Human genes 0.000 description 1
- 102220471075 Carcinoembryonic antigen-related cell adhesion molecule 5_E133A_mutation Human genes 0.000 description 1
- 102220471079 Carcinoembryonic antigen-related cell adhesion molecule 5_I125A_mutation Human genes 0.000 description 1
- 102220470969 Carcinoembryonic antigen-related cell adhesion molecule 5_V73A_mutation Human genes 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102220634221 Casein kinase I isoform alpha-like_T43Q_mutation Human genes 0.000 description 1
- 102220595198 Casein kinase II subunit alpha'-interacting protein_M87Y_mutation Human genes 0.000 description 1
- 102220553803 Caspase recruitment domain-containing protein 8_I58A_mutation Human genes 0.000 description 1
- 102220495333 Caspase-5_K182I_mutation Human genes 0.000 description 1
- 102220584676 Catechol O-methyltransferase_M181A_mutation Human genes 0.000 description 1
- 102220574879 Cation channel sperm-associated auxiliary subunit epsilon_T66K_mutation Human genes 0.000 description 1
- 241000863012 Caulobacter Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102220572741 Cbp/p300-interacting transactivator 1_L165A_mutation Human genes 0.000 description 1
- 102220572749 Cbp/p300-interacting transactivator 1_L176A_mutation Human genes 0.000 description 1
- 102220504724 Cdc42 effector protein 2_I191F_mutation Human genes 0.000 description 1
- 102220531744 Cell surface hyaluronidase_G224I_mutation Human genes 0.000 description 1
- 102220546087 Cell surface hyaluronidase_K124A_mutation Human genes 0.000 description 1
- 102220582871 Cellular tumor antigen p53_A39P_mutation Human genes 0.000 description 1
- 102220522546 Cellular tumor antigen p53_G187C_mutation Human genes 0.000 description 1
- 102220522540 Cellular tumor antigen p53_G187N_mutation Human genes 0.000 description 1
- 102220522503 Cellular tumor antigen p53_G187S_mutation Human genes 0.000 description 1
- 102220522507 Cellular tumor antigen p53_G187V_mutation Human genes 0.000 description 1
- 102220566892 Cellular tumor antigen p53_G262C_mutation Human genes 0.000 description 1
- 102220566891 Cellular tumor antigen p53_G262D_mutation Human genes 0.000 description 1
- 102220566900 Cellular tumor antigen p53_G262H_mutation Human genes 0.000 description 1
- 102220574824 Cellular tumor antigen p53_K120M_mutation Human genes 0.000 description 1
- 102220574822 Cellular tumor antigen p53_K120R_mutation Human genes 0.000 description 1
- 102220575233 Cellular tumor antigen p53_N131D_mutation Human genes 0.000 description 1
- 102220575234 Cellular tumor antigen p53_N131H_mutation Human genes 0.000 description 1
- 102220551923 Cellular tumor antigen p53_P222A_mutation Human genes 0.000 description 1
- 102220551874 Cellular tumor antigen p53_P222Q_mutation Human genes 0.000 description 1
- 102220551865 Cellular tumor antigen p53_P222R_mutation Human genes 0.000 description 1
- 102220551875 Cellular tumor antigen p53_P222T_mutation Human genes 0.000 description 1
- 102220584231 Cellular tumor antigen p53_P77A_mutation Human genes 0.000 description 1
- 102220575718 Cellular tumor antigen p53_R174M_mutation Human genes 0.000 description 1
- 102220575716 Cellular tumor antigen p53_R174T_mutation Human genes 0.000 description 1
- 102220575713 Cellular tumor antigen p53_R174W_mutation Human genes 0.000 description 1
- 102220549651 Cellular tumor antigen p53_R213W_mutation Human genes 0.000 description 1
- 102220565164 Cellular tumor antigen p53_S240P_mutation Human genes 0.000 description 1
- 102220587394 Cellular tumor antigen p53_S96C_mutation Human genes 0.000 description 1
- 102220583897 Cellular tumor antigen p53_S96F_mutation Human genes 0.000 description 1
- 102220583904 Cellular tumor antigen p53_S96P_mutation Human genes 0.000 description 1
- 102220573636 Cellular tumor antigen p53_T150K_mutation Human genes 0.000 description 1
- 102220573634 Cellular tumor antigen p53_T150N_mutation Human genes 0.000 description 1
- 102220573632 Cellular tumor antigen p53_T150R_mutation Human genes 0.000 description 1
- 102220572065 Cellular tumor antigen p53_V157G_mutation Human genes 0.000 description 1
- 102220572063 Cellular tumor antigen p53_V157L_mutation Human genes 0.000 description 1
- 102220584270 Cellular tumor antigen p53_V73E_mutation Human genes 0.000 description 1
- 102220584269 Cellular tumor antigen p53_V73L_mutation Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102220607389 Cerebral cavernous malformations 2 protein_L229Q_mutation Human genes 0.000 description 1
- 102220598158 Ceroid-lipofuscinosis neuronal protein 5_N143Q_mutation Human genes 0.000 description 1
- 241000195649 Chlorella <Chlorellales> Species 0.000 description 1
- 240000009108 Chlorella vulgaris Species 0.000 description 1
- 235000007089 Chlorella vulgaris Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000195628 Chlorophyta Species 0.000 description 1
- 102220607107 Choline transporter-like protein 1_D179Q_mutation Human genes 0.000 description 1
- 102220626948 Choline transporter-like protein 2_K119T_mutation Human genes 0.000 description 1
- 102220550848 Chromatin modification-related protein MEAF6_I58S_mutation Human genes 0.000 description 1
- 241000588881 Chromobacterium Species 0.000 description 1
- 102220504991 Chymotrypsin-C_A257T_mutation Human genes 0.000 description 1
- 102220503654 Chymotrypsin-C_D35H_mutation Human genes 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 102220579680 Claudin-1_A39R_mutation Human genes 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000193171 Clostridium butyricum Species 0.000 description 1
- 102220627832 Coagulation factor IX_I112S_mutation Human genes 0.000 description 1
- 102220570326 Coagulation factor IX_V227D_mutation Human genes 0.000 description 1
- 102220627584 Coagulation factor IX_V30I_mutation Human genes 0.000 description 1
- 102220527740 Coagulation factor VIII_D101V_mutation Human genes 0.000 description 1
- 102220519408 Coatomer subunit alpha_P221A_mutation Human genes 0.000 description 1
- 102220635487 Cochlin_N76Y_mutation Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102220496392 Coiled-coil domain-containing protein 102A_T130C_mutation Human genes 0.000 description 1
- 102220546571 Coiled-coil domain-containing protein 27_Q54E_mutation Human genes 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102220600350 Collagen alpha-1(I) chain_G224C_mutation Human genes 0.000 description 1
- 241000589519 Comamonas Species 0.000 description 1
- 102220608863 Conserved oligomeric Golgi complex subunit 8_L169K_mutation Human genes 0.000 description 1
- 102220608860 Conserved oligomeric Golgi complex subunit 8_Q55E_mutation Human genes 0.000 description 1
- 102220608859 Conserved oligomeric Golgi complex subunit 8_S117A_mutation Human genes 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 102220607655 Cullin-associated NEDD8-dissociated protein 2_L9A_mutation Human genes 0.000 description 1
- 102220591849 Cullin-associated NEDD8-dissociated protein 2_V195I_mutation Human genes 0.000 description 1
- 102220553685 Cyclic GMP-AMP synthase_K173A_mutation Human genes 0.000 description 1
- 102220553678 Cyclic GMP-AMP synthase_K173R_mutation Human genes 0.000 description 1
- 102220553722 Cyclic GMP-AMP synthase_K252E_mutation Human genes 0.000 description 1
- 102220553647 Cyclic GMP-AMP synthase_T130E_mutation Human genes 0.000 description 1
- 102220553774 Cyclic GMP-AMP synthase_T68E_mutation Human genes 0.000 description 1
- 102220597630 Cyclin-dependent kinase inhibitor 1C_L53P_mutation Human genes 0.000 description 1
- 102220503738 Cyclin-dependent kinase inhibitor 2A_D14E_mutation Human genes 0.000 description 1
- 102220598781 Cyclin-dependent kinase-like 5_T158D_mutation Human genes 0.000 description 1
- 102220598604 Cyclin-dependent kinase-like 5_T158V_mutation Human genes 0.000 description 1
- 102220492761 Cystatin-M_I218M_mutation Human genes 0.000 description 1
- 102220599250 Cysteine and histidine-rich domain-containing protein 1_A217G_mutation Human genes 0.000 description 1
- 102220583471 Cysteine-rich secretory protein 1_S100D_mutation Human genes 0.000 description 1
- 102220587546 Cysteinyl leukotriene receptor 1_S42D_mutation Human genes 0.000 description 1
- 102220497455 Cytochrome P450 11B2, mitochondrial_I112P_mutation Human genes 0.000 description 1
- 102220608885 Cytochrome P450 27C1_K90I_mutation Human genes 0.000 description 1
- 102220527031 Cytochrome b5 reductase 4_T66S_mutation Human genes 0.000 description 1
- 102220527032 Cytochrome b5 reductase 4_T66V_mutation Human genes 0.000 description 1
- 102220644482 Cytochrome b_I78V_mutation Human genes 0.000 description 1
- 102220641073 Cytochrome b_S159A_mutation Human genes 0.000 description 1
- 102220584780 Cytochrome c oxidase subunit 8A, mitochondrial_N143I_mutation Human genes 0.000 description 1
- 102220620548 Cytokine receptor-like factor 1_Y75D_mutation Human genes 0.000 description 1
- 102220487231 Cytoplasmic FMR1-interacting protein 1_M260I_mutation Human genes 0.000 description 1
- 102220523212 Cytoplasmic tyrosine-protein kinase BMX_L122H_mutation Human genes 0.000 description 1
- 102220606260 Cytosolic arginine sensor for mTORC1 subunit 2_D14A_mutation Human genes 0.000 description 1
- 102220607647 Cytosolic arginine sensor for mTORC1 subunit 2_Q111N_mutation Human genes 0.000 description 1
- 102220519474 Cytosolic phospholipase A2 gamma_H82N_mutation Human genes 0.000 description 1
- 102220503788 Cytotoxic T-lymphocyte protein 4_L47D_mutation Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102220581497 DNA dC->dU-editing enzyme APOBEC-3G_R213E_mutation Human genes 0.000 description 1
- 102220578534 DNA helicase MCM8_Q63K_mutation Human genes 0.000 description 1
- 102220490510 DNA mismatch repair protein Mlh3_A41F_mutation Human genes 0.000 description 1
- 102220490511 DNA mismatch repair protein Mlh3_A41G_mutation Human genes 0.000 description 1
- 102220490416 DNA mismatch repair protein Mlh3_A41S_mutation Human genes 0.000 description 1
- 102220525524 DNA polymerase delta catalytic subunit_D236N_mutation Human genes 0.000 description 1
- 102220552539 DNA primase small subunit_K256C_mutation Human genes 0.000 description 1
- 102220555200 DNA topoisomerase 3-alpha_D23R_mutation Human genes 0.000 description 1
- 102220641188 DNA-dependent metalloprotease SPRTN_L109R_mutation Human genes 0.000 description 1
- 102220569994 DNA-directed RNA polymerase, mitochondrial_D236N_mutation Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102220518119 DNA-directed RNA polymerases I and III subunit RPAC1_E1R_mutation Human genes 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 241001030162 Debaryomyces sp. Species 0.000 description 1
- 102220598051 Dehydrodolichyl diphosphate synthase complex subunit DHDDS_I19A_mutation Human genes 0.000 description 1
- 102220548576 Delta and Notch-like epidermal growth factor-related receptor_P34F_mutation Human genes 0.000 description 1
- 102220548598 Delta and Notch-like epidermal growth factor-related receptor_Y32A_mutation Human genes 0.000 description 1
- 102220480435 Deoxyhypusine synthase_D243A_mutation Human genes 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 102220559716 Differentially expressed in FDCP 8 homolog_Y67G_mutation Human genes 0.000 description 1
- 102220531664 Dihydropyrimidinase_T68R_mutation Human genes 0.000 description 1
- 102220604368 Dipeptidase 1_E141C_mutation Human genes 0.000 description 1
- 102220511738 Dipeptidyl peptidase 1_D236Y_mutation Human genes 0.000 description 1
- 102220511723 Dipeptidyl peptidase 1_V129E_mutation Human genes 0.000 description 1
- 102220511748 Dipeptidyl peptidase 1_Y210D_mutation Human genes 0.000 description 1
- 102220511746 Dipeptidyl peptidase 1_Y210F_mutation Human genes 0.000 description 1
- 102220483252 Diphosphoinositol polyphosphate phosphohydrolase 2_F40A_mutation Human genes 0.000 description 1
- 102220610778 Diphosphomevalonate decarboxylase_R161L_mutation Human genes 0.000 description 1
- 102220582589 Disintegrin and metalloproteinase domain-containing protein 29_S234F_mutation Human genes 0.000 description 1
- 102220499648 DnaJ homolog subfamily C member 2_Y99A_mutation Human genes 0.000 description 1
- 102220578419 Doublesex- and mab-3-related transcription factor 3_N261T_mutation Human genes 0.000 description 1
- 102220563203 Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide_K173L_mutation Human genes 0.000 description 1
- 102220465711 Dual specificity tyrosine-phosphorylation-regulated kinase 1B_D239A_mutation Human genes 0.000 description 1
- 102220511304 Dual specificity tyrosine-phosphorylation-regulated kinase 3_K238M_mutation Human genes 0.000 description 1
- 102220477047 Dynein axonemal assembly factor 10_N76G_mutation Human genes 0.000 description 1
- 102220521714 Dynein light chain 2, cytoplasmic_D167K_mutation Human genes 0.000 description 1
- 102220519690 Dynein light chain Tctex-type 3_A153G_mutation Human genes 0.000 description 1
- 102220467460 Dynein regulatory complex protein 11_K8M_mutation Human genes 0.000 description 1
- 102220499627 Dysferlin_D71A_mutation Human genes 0.000 description 1
- 102220548055 Dystrophin_E141A_mutation Human genes 0.000 description 1
- 102220538870 E3 ubiquitin-protein ligase BRE1B_L109S_mutation Human genes 0.000 description 1
- 102220482304 E3 ubiquitin-protein ligase DCST1_E138D_mutation Human genes 0.000 description 1
- 102220482305 E3 ubiquitin-protein ligase DCST1_E138Q_mutation Human genes 0.000 description 1
- 102220480814 E3 ubiquitin-protein ligase DCST1_K81A_mutation Human genes 0.000 description 1
- 102220579943 E3 ubiquitin-protein ligase RING2_R98A_mutation Human genes 0.000 description 1
- 102220625394 E3 ubiquitin-protein ligase RNF31_N102A_mutation Human genes 0.000 description 1
- 102220508341 E3 ubiquitin-protein ligase XIAP_Y75G_mutation Human genes 0.000 description 1
- 102220473766 ELAV-like protein 1_T185Y_mutation Human genes 0.000 description 1
- 102220473803 ELAV-like protein 1_Y75T_mutation Human genes 0.000 description 1
- 102220500686 ELMO domain-containing protein 2_K245N_mutation Human genes 0.000 description 1
- 102220561049 ENTH domain-containing protein 1_D244R_mutation Human genes 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 102220499208 Echinoderm microtubule-associated protein-like 1_R192S_mutation Human genes 0.000 description 1
- 102220476047 Ectodysplasin-A_G198A_mutation Human genes 0.000 description 1
- 102220473529 Ectopic P granules protein 5 homolog_A193L_mutation Human genes 0.000 description 1
- 102220473501 Ectopic P granules protein 5 homolog_D244A_mutation Human genes 0.000 description 1
- 102220516209 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial_Q55C_mutation Human genes 0.000 description 1
- 102220635184 Elongation factor G, mitochondrial_S57Y_mutation Human genes 0.000 description 1
- 102220508128 Endogenous retrovirus group K member 6 Rec protein_K124I_mutation Human genes 0.000 description 1
- 102220545601 Endonuclease III-like protein 1_D239Y_mutation Human genes 0.000 description 1
- 102220545606 Endonuclease III-like protein 1_R33K_mutation Human genes 0.000 description 1
- 102220511100 Endothelial cell-specific molecule 1_M2I_mutation Human genes 0.000 description 1
- 102220472614 Endothelin-1_K90T_mutation Human genes 0.000 description 1
- 102220518444 Enhancer of filamentation 1_T29I_mutation Human genes 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 241000195620 Euglena Species 0.000 description 1
- 102220542938 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A_S233G_mutation Human genes 0.000 description 1
- 102220542941 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A_S233T_mutation Human genes 0.000 description 1
- 102220542222 Eukaryotic peptide chain release factor GTP-binding subunit ERF3B_L52K_mutation Human genes 0.000 description 1
- 102220505066 Eukaryotic translation initiation factor 3 subunit B_L89Y_mutation Human genes 0.000 description 1
- 102220628817 Eukaryotic translation initiation factor 5A-2_G50P_mutation Human genes 0.000 description 1
- 102220496254 Exocyst complex component 3-like protein_Y75N_mutation Human genes 0.000 description 1
- 102220636289 Exopolyphosphatase PRUNE1_F163Y_mutation Human genes 0.000 description 1
- 102220636076 Exopolyphosphatase PRUNE1_I219A_mutation Human genes 0.000 description 1
- 102220646250 Exosome complex exonuclease RRP44_K173T_mutation Human genes 0.000 description 1
- 102220615108 Extracellular calcium-sensing receptor_D215G_mutation Human genes 0.000 description 1
- 102220615228 Extracellular calcium-sensing receptor_N102I_mutation Human genes 0.000 description 1
- 102220615227 Extracellular calcium-sensing receptor_R69E_mutation Human genes 0.000 description 1
- 102220615097 Extracellular calcium-sensing receptor_S171N_mutation Human genes 0.000 description 1
- 102220583772 Extracellular matrix protein 1_T130M_mutation Human genes 0.000 description 1
- 102220605791 F-actin-capping protein subunit alpha-1_F163I_mutation Human genes 0.000 description 1
- 102220511795 F-actin-capping protein subunit beta_A207Y_mutation Human genes 0.000 description 1
- 102220568902 F-box/LRR-repeat protein 2_D149C_mutation Human genes 0.000 description 1
- 102220564963 FAD synthase region_K245M_mutation Human genes 0.000 description 1
- 102220625746 FAD-linked sulfhydryl oxidase ALR_S234N_mutation Human genes 0.000 description 1
- 102220510254 FAS-associated death domain protein_L176E_mutation Human genes 0.000 description 1
- 102220546867 Fanconi anemia group C protein_L190F_mutation Human genes 0.000 description 1
- 102220545082 Far upstream element-binding protein 1_L89S_mutation Human genes 0.000 description 1
- 102220467701 Ferrochelatase, mitochondrial_E172G_mutation Human genes 0.000 description 1
- 102220551864 Fibroblast growth factor 13_E1A_mutation Human genes 0.000 description 1
- 102220573434 Fibroblast growth factor 22_D14C_mutation Human genes 0.000 description 1
- 102220597432 Fizzy-related protein homolog_S151A_mutation Human genes 0.000 description 1
- 241000589565 Flavobacterium Species 0.000 description 1
- 102220560989 Flotillin-2_D167R_mutation Human genes 0.000 description 1
- 102220560986 Flotillin-2_L160D_mutation Human genes 0.000 description 1
- 102220560990 Flotillin-2_L160E_mutation Human genes 0.000 description 1
- 102220566405 Folylpolyglutamate synthase, mitochondrial_A155H_mutation Human genes 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102220500669 Formylglycine-generating enzyme_K173G_mutation Human genes 0.000 description 1
- 102220500614 Formylglycine-generating enzyme_N259I_mutation Human genes 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102220465687 Fructose-bisphosphate aldolase B_R134S_mutation Human genes 0.000 description 1
- 102220575486 Fucose mutarotase_R174D_mutation Human genes 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 102220564662 GDP-fucose transporter 1_F135E_mutation Human genes 0.000 description 1
- 102220620100 GPI ethanolamine phosphate transferase 3_T130N_mutation Human genes 0.000 description 1
- 102220483961 GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1_S159D_mutation Human genes 0.000 description 1
- 102220582022 GTP cyclohydrolase 1_T186K_mutation Human genes 0.000 description 1
- 102220616650 GTP-binding nuclear protein Ran_T24L_mutation Human genes 0.000 description 1
- 102220532888 GTP-binding protein Rheb_D60I_mutation Human genes 0.000 description 1
- 102220605904 GTPase HRas_P34G_mutation Human genes 0.000 description 1
- 102220605905 GTPase HRas_Y32F_mutation Human genes 0.000 description 1
- 102220631430 GTPase IMAP family member 7_E136W_mutation Human genes 0.000 description 1
- 102220570391 Galactocerebrosidase_G194A_mutation Human genes 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 102220568810 Galactose-3-O-sulfotransferase 3_L232M_mutation Human genes 0.000 description 1
- 102220474042 Galectin-9C_N131D_mutation Human genes 0.000 description 1
- 102220607146 Gap junction beta-1 protein_L9W_mutation Human genes 0.000 description 1
- 102220486953 Gap junction beta-1 protein_R183S_mutation Human genes 0.000 description 1
- 102220594389 Gap junction beta-1 protein_T130I_mutation Human genes 0.000 description 1
- 102220507961 Gasdermin-E_R154A_mutation Human genes 0.000 description 1
- 102220558028 Gem-associated protein 2_R213D_mutation Human genes 0.000 description 1
- 102220498724 General transcription factor IIE subunit 1_T186N_mutation Human genes 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 241000626621 Geobacillus Species 0.000 description 1
- 241001135750 Geobacter Species 0.000 description 1
- 102220601686 Gliomedin_L156H_mutation Human genes 0.000 description 1
- SWDSRANUCKNBLA-AVGNSLFASA-N Gln-Phe-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N SWDSRANUCKNBLA-AVGNSLFASA-N 0.000 description 1
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 1
- SOEPMWQCTJITPZ-SRVKXCTJSA-N Glu-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N SOEPMWQCTJITPZ-SRVKXCTJSA-N 0.000 description 1
- 102220543465 Glucagon-like peptide 1 receptor_E128Q_mutation Human genes 0.000 description 1
- 102220558019 Glucocorticoid receptor_D101K_mutation Human genes 0.000 description 1
- 241000589236 Gluconobacter Species 0.000 description 1
- 102220555339 Glutamate carboxypeptidase 2_N76A_mutation Human genes 0.000 description 1
- 102220555337 Glutamate carboxypeptidase 2_Y75H_mutation Human genes 0.000 description 1
- 102220533602 Glutamine and serine-rich protein 1_V157E_mutation Human genes 0.000 description 1
- 102220495643 Glutaredoxin-like protein C5orf63_K119N_mutation Human genes 0.000 description 1
- 102220600921 Glutathione-specific gamma-glutamylcyclotransferase 2_N214K_mutation Human genes 0.000 description 1
- FCKPEGOCSVZPNC-WHOFXGATSA-N Gly-Ile-Phe Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FCKPEGOCSVZPNC-WHOFXGATSA-N 0.000 description 1
- 102220534759 Glycogen phosphorylase, liver form_T26V_mutation Human genes 0.000 description 1
- 102220534026 Glycogen phosphorylase, liver form_V231E_mutation Human genes 0.000 description 1
- 102220643428 Glycogenin-2_G194R_mutation Human genes 0.000 description 1
- 102220644332 Glycogenin-2_R235L_mutation Human genes 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 102220485772 Glycophorin-A_E91C_mutation Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 102220480575 Gremlin-1_K252A_mutation Human genes 0.000 description 1
- 102220592685 Guanidinoacetate N-methyltransferase_L258A_mutation Human genes 0.000 description 1
- 102220592690 Guanidinoacetate N-methyltransferase_L258G_mutation Human genes 0.000 description 1
- 102220487369 Guanine nucleotide-binding protein G(i) subunit alpha-1_E116L_mutation Human genes 0.000 description 1
- 102220520020 Guanylyl cyclase-activating protein 1_L246A_mutation Human genes 0.000 description 1
- 102220519038 Guanylyl cyclase-activating protein 1_Y99N_mutation Human genes 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102220576268 HLA class I histocompatibility antigen, A alpha chain_K168Q_mutation Human genes 0.000 description 1
- 102220575538 HLA class I histocompatibility antigen, A alpha chain_T158K_mutation Human genes 0.000 description 1
- 102220576103 HLA class I histocompatibility antigen, B alpha chain_A15G_mutation Human genes 0.000 description 1
- 102220576058 HLA class I histocompatibility antigen, B alpha chain_A93R_mutation Human genes 0.000 description 1
- 102220593933 HLA class I histocompatibility antigen, alpha chain G_E138H_mutation Human genes 0.000 description 1
- 102220500520 HLA class II histocompatibility antigen, DM beta chain_A162E_mutation Human genes 0.000 description 1
- 102220467950 HLA class II histocompatibility antigen, DP beta 1 chain_A31L_mutation Human genes 0.000 description 1
- 102220467946 HLA class II histocompatibility antigen, DP beta 1 chain_F38D_mutation Human genes 0.000 description 1
- 102220467947 HLA class II histocompatibility antigen, DP beta 1 chain_F38H_mutation Human genes 0.000 description 1
- 102220467933 HLA class II histocompatibility antigen, DP beta 1 chain_F38L_mutation Human genes 0.000 description 1
- 102220467934 HLA class II histocompatibility antigen, DP beta 1 chain_F38Y_mutation Human genes 0.000 description 1
- 102220468011 HLA class II histocompatibility antigen, DP beta 1 chain_G113D_mutation Human genes 0.000 description 1
- 102220468007 HLA class II histocompatibility antigen, DP beta 1 chain_P115A_mutation Human genes 0.000 description 1
- 102220467912 HLA class II histocompatibility antigen, DP beta 1 chain_T24I_mutation Human genes 0.000 description 1
- 102220545757 HLA class II histocompatibility antigen, DQ alpha 1 chain_V73D_mutation Human genes 0.000 description 1
- 102220498341 HLA class II histocompatibility antigen, DRB1 beta chain_A103E_mutation Human genes 0.000 description 1
- 102220498326 HLA class II histocompatibility antigen, DRB1 beta chain_A103L_mutation Human genes 0.000 description 1
- 102220498327 HLA class II histocompatibility antigen, DRB1 beta chain_A103Q_mutation Human genes 0.000 description 1
- 102220498324 HLA class II histocompatibility antigen, DRB1 beta chain_A103R_mutation Human genes 0.000 description 1
- 102220498307 HLA class II histocompatibility antigen, DRB1 beta chain_E166A_mutation Human genes 0.000 description 1
- 241000206759 Haptophyceae Species 0.000 description 1
- 102220626282 Hemoglobin subunit alpha_D127G_mutation Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 102220605090 Hemoglobin subunit beta_A202D_mutation Human genes 0.000 description 1
- 102220606740 Hemoglobin subunit beta_N140S_mutation Human genes 0.000 description 1
- 102220622871 Hemoglobin subunit delta_V30L_mutation Human genes 0.000 description 1
- 102220582682 Heparan sulfate glucosamine 3-O-sulfotransferase 5_I247N_mutation Human genes 0.000 description 1
- 102220509201 Heparin cofactor 2_K204M_mutation Human genes 0.000 description 1
- 102220509202 Heparin cofactor 2_K204N_mutation Human genes 0.000 description 1
- 102220508970 Heparin cofactor 2_K204T_mutation Human genes 0.000 description 1
- 102220491237 Heterochromatin protein 1-binding protein 3_E136P_mutation Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102220565940 Hexokinase HKDC1_K245E_mutation Human genes 0.000 description 1
- 102220633198 Hexokinase-4_D4N_mutation Human genes 0.000 description 1
- 102220633168 Hexokinase-4_I19N_mutation Human genes 0.000 description 1
- 102220633335 Hexokinase-4_S151T_mutation Human genes 0.000 description 1
- 102220491973 High mobility group protein B1_I191A_mutation Human genes 0.000 description 1
- 102220491780 High mobility group protein B1_R123A_mutation Human genes 0.000 description 1
- 102220491824 High mobility group protein B1_S42E_mutation Human genes 0.000 description 1
- 102220521380 Histo-blood group ABO system transferase_L22I_mutation Human genes 0.000 description 1
- 102220628501 Histone H1.1_D94H_mutation Human genes 0.000 description 1
- 102220628523 Histone H1.1_D94N_mutation Human genes 0.000 description 1
- 102220609221 Histone H1.1_T152E_mutation Human genes 0.000 description 1
- 102220585137 Histone H1t_K110V_mutation Human genes 0.000 description 1
- 102220466683 Histone H4 transcription factor_Q105P_mutation Human genes 0.000 description 1
- 102220470743 Histone deacetylase 7_M181H_mutation Human genes 0.000 description 1
- 102220470982 Histone deacetylase 8_D101L_mutation Human genes 0.000 description 1
- 102220596678 Histone-lysine N-methyltransferase SETD1B_V129G_mutation Human genes 0.000 description 1
- 102220588775 Histone-lysine N-methyltransferase, H3 lysine-79 specific_L107T_mutation Human genes 0.000 description 1
- 102220588776 Histone-lysine N-methyltransferase, H3 lysine-79 specific_M87H_mutation Human genes 0.000 description 1
- 102220588739 Histone-lysine N-methyltransferase, H3 lysine-79 specific_M87I_mutation Human genes 0.000 description 1
- 102220590197 Homeobox protein TGIF2_T186V_mutation Human genes 0.000 description 1
- 102220609910 Homeobox protein VENTX_L72I_mutation Human genes 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 102220517941 Humanin_L9R_mutation 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
- 102220475419 Iduronate 2-sulfatase_S117Y_mutation Human genes 0.000 description 1
- HQEPKOFULQTSFV-JURCDPSOSA-N Ile-Phe-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)O)N HQEPKOFULQTSFV-JURCDPSOSA-N 0.000 description 1
- 102220545595 Ileal sodium/bile acid cotransporter_S171A_mutation Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102220628895 Immediate early response gene 2 protein_R235E_mutation Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102220617353 Immunoglobulin heavy constant gamma 1_L118E_mutation Human genes 0.000 description 1
- 102220478028 Immunoglobulin lambda variable 10-54_D4K_mutation Human genes 0.000 description 1
- 102220474407 Importin subunit beta-1_I178A_mutation Human genes 0.000 description 1
- 102220474408 Importin subunit beta-1_I178D_mutation Human genes 0.000 description 1
- 102220498572 InaD-like protein_F38W_mutation Human genes 0.000 description 1
- 102220632330 Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2_P196A_mutation Human genes 0.000 description 1
- 102220636814 Inactive rhomboid protein 1_N131Q_mutation Human genes 0.000 description 1
- 102220635687 Inner centromere protein_E36R_mutation Human genes 0.000 description 1
- 102220474121 Inorganic pyrophosphatase 2, mitochondrial_I19T_mutation Human genes 0.000 description 1
- 102220641838 Inorganic pyrophosphatase_N102H_mutation Human genes 0.000 description 1
- 102220468816 Inositol 1,4,5-trisphosphate receptor type 2_L169A_mutation Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102220583202 Insulin-degrading enzyme_N184C_mutation Human genes 0.000 description 1
- 102220509927 Insulin-induced gene 2 protein_S151E_mutation Human genes 0.000 description 1
- 102220465481 Insulin-like growth factor II_K120N_mutation Human genes 0.000 description 1
- 102220468768 Insulin-like growth factor-binding protein 6_R134L_mutation Human genes 0.000 description 1
- 102220528921 Integrin beta-3_D243V_mutation Human genes 0.000 description 1
- 102220624326 Interferon alpha-8_N106P_mutation Human genes 0.000 description 1
- 102220465288 Interferon alpha-8_W180A_mutation Human genes 0.000 description 1
- 102220618069 Interferon-induced protein 44-like_K110L_mutation Human genes 0.000 description 1
- 102220478629 Interleukin-1 beta_E141N_mutation Human genes 0.000 description 1
- 102220637846 Interleukin-1 receptor-associated kinase-like 2_T66E_mutation Human genes 0.000 description 1
- 102220465506 Interleukin-33_D149K_mutation Human genes 0.000 description 1
- 102220465488 Interleukin-33_D244K_mutation Human genes 0.000 description 1
- 102220487959 Isoaspartyl peptidase/L-asparaginase_T147E_mutation Human genes 0.000 description 1
- 102220517092 Jerky protein homolog-like_P132S_mutation Human genes 0.000 description 1
- 102220475429 Junctional protein associated with coronary artery disease_D215S_mutation Human genes 0.000 description 1
- 102220517657 KAT8 regulatory NSL complex subunit 3_T24F_mutation Human genes 0.000 description 1
- 102220561296 KH homology domain-containing protein 4_S151D_mutation Human genes 0.000 description 1
- 102220511586 Kappa-casein_D84R_mutation Human genes 0.000 description 1
- 102220477973 Kelch-like protein 4_A207E_mutation Human genes 0.000 description 1
- 102220475922 Keratin, type I cytoskeletal 10_D4A_mutation Human genes 0.000 description 1
- 102220475927 Keratin, type I cytoskeletal 10_F6A_mutation Human genes 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102220509244 Ketohexokinase_V129F_mutation Human genes 0.000 description 1
- 102220565460 Killer cell immunoglobulin-like receptor 2DL2_A15Q_mutation Human genes 0.000 description 1
- 102220525251 Killer cell lectin-like receptor subfamily B member 1_S151G_mutation Human genes 0.000 description 1
- 102220529399 Kinectin_T152D_mutation Human genes 0.000 description 1
- 101000740455 Klebsiella pneumoniae Metallo-beta-lactamase type 2 Proteins 0.000 description 1
- 102220516685 Kynurenine-oxoglutarate transaminase 1_G262K_mutation Human genes 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
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-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
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- XIGSAGMEBXLVJJ-YFKPBYRVSA-N L-homocitrulline Chemical compound NC(=O)NCCCC[C@H]([NH3+])C([O-])=O XIGSAGMEBXLVJJ-YFKPBYRVSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- 238000007397 LAMP assay Methods 0.000 description 1
- 102220637763 LIM domain kinase 1_Y242F_mutation Human genes 0.000 description 1
- 102220596106 LINE-1 retrotransposable element ORF1 protein_I218Y_mutation Human genes 0.000 description 1
- 102220596114 LINE-1 retrotransposable element ORF1 protein_R235A_mutation Human genes 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 240000006024 Lactobacillus plantarum Species 0.000 description 1
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- 206010023804 Large intestine perforation Diseases 0.000 description 1
- 102220531101 Left-right determination factor 1_L92S_mutation Human genes 0.000 description 1
- WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 description 1
- NHRINZSPIUXYQZ-DCAQKATOSA-N Leu-Met-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CS)C(=O)O)N NHRINZSPIUXYQZ-DCAQKATOSA-N 0.000 description 1
- YUTNOGOMBNYPFH-XUXIUFHCSA-N Leu-Pro-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YUTNOGOMBNYPFH-XUXIUFHCSA-N 0.000 description 1
- 102220557547 Leucine-rich repeat transmembrane protein FLRT3_D188T_mutation Human genes 0.000 description 1
- 102220618932 Leucine-rich repeat-containing protein 34_A95G_mutation Human genes 0.000 description 1
- 102220599168 Leukemia inhibitory factor_N76F_mutation Human genes 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 102220520945 Linker for activation of T-cells family member 2_K263S_mutation Human genes 0.000 description 1
- 102220553019 Lipoprotein lipase_S159G_mutation Human genes 0.000 description 1
- 102220551000 Lipoprotein lipase_V227A_mutation Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001625930 Luria Species 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 102220465649 Lymphocyte activation gene 3 protein_Y99F_mutation Human genes 0.000 description 1
- 102220496740 Lymphocyte expansion molecule_G126C_mutation Human genes 0.000 description 1
- 102220496737 Lymphocyte function-associated antigen 3_V49Q_mutation Human genes 0.000 description 1
- SJNZALDHDUYDBU-IHRRRGAJSA-N Lys-Arg-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(O)=O SJNZALDHDUYDBU-IHRRRGAJSA-N 0.000 description 1
- QUYCUALODHJQLK-CIUDSAMLSA-N Lys-Asp-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O QUYCUALODHJQLK-CIUDSAMLSA-N 0.000 description 1
- VMTYLUGCXIEDMV-QWRGUYRKSA-N Lys-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCCCN VMTYLUGCXIEDMV-QWRGUYRKSA-N 0.000 description 1
- 102220639882 Lysine-specific demethylase RSBN1L_I65P_mutation Human genes 0.000 description 1
- 102220644371 Lysophosphatidic acid phosphatase type 6_A257L_mutation Human genes 0.000 description 1
- 102220644370 Lysophosphatidic acid phosphatase type 6_A257W_mutation Human genes 0.000 description 1
- 102220553275 Lysosomal acid glucosylceramidase_E80K_mutation Human genes 0.000 description 1
- 102220641423 Lysosomal alpha-mannosidase_A250S_mutation Human genes 0.000 description 1
- 102220569980 MHC class I polypeptide-related sequence A_T147S_mutation Human genes 0.000 description 1
- 102220570016 MHC class I polypeptide-related sequence A_V49G_mutation Human genes 0.000 description 1
- 102220507166 MICOS complex subunit MIC25_A95S_mutation Human genes 0.000 description 1
- 102220507276 MKI67 FHA domain-interacting nucleolar phosphoprotein_P144Q_mutation Human genes 0.000 description 1
- 102220501901 MOB kinase activator 1B_T251S_mutation Human genes 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 102220637794 MRN complex-interacting protein_R154G_mutation Human genes 0.000 description 1
- 102220583218 Macrophage migration inhibitory factor_I65A_mutation Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102220611302 Magnesium transporter MRS2 homolog, mitochondrial_L61K_mutation Human genes 0.000 description 1
- 102220611300 Magnesium transporter MRS2 homolog, mitochondrial_L97D_mutation Human genes 0.000 description 1
- 102220619525 Major facilitator superfamily domain-containing protein 6-like_T186E_mutation Human genes 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102220582826 Mannose-binding protein C_N214Y_mutation Human genes 0.000 description 1
- 101710084218 Master replication protein Proteins 0.000 description 1
- 102220573527 Matrix metalloproteinase-21_P115Q_mutation Human genes 0.000 description 1
- 102220621066 Medium-chain acyl-CoA ligase ACSF2, mitochondrial_D188P_mutation Human genes 0.000 description 1
- 102220562622 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial_I108M_mutation Human genes 0.000 description 1
- 102220550687 Megakaryocyte and platelet inhibitory receptor G6b_L190A_mutation Human genes 0.000 description 1
- 102220579522 Melanocyte-stimulating hormone receptor_K238R_mutation Human genes 0.000 description 1
- 102220522927 Melanoma-associated antigen C3_L165M_mutation Human genes 0.000 description 1
- 102220514508 Membrane-bound transcription factor site-2 protease_E172D_mutation Human genes 0.000 description 1
- 102220507843 Menin_S159I_mutation Human genes 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 102220639895 Mesencephalic astrocyte-derived neurotrophic factor_L109Q_mutation Human genes 0.000 description 1
- RVYDCISQIGHAFC-ZPFDUUQYSA-N Met-Ile-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O RVYDCISQIGHAFC-ZPFDUUQYSA-N 0.000 description 1
- 102220548782 Metalloproteinase inhibitor 4_D4R_mutation Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 102220526795 Methenyltetrahydrofolate cyclohydrolase_D225E_mutation Human genes 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 102220562494 Methylosome subunit pICln_S171Y_mutation Human genes 0.000 description 1
- 102220562506 Methylosome subunit pICln_T251Y_mutation Human genes 0.000 description 1
- 102220507944 Methyltransferase-like protein 27_S171W_mutation Human genes 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102220528252 Microfibrillar-associated protein 2_T79V_mutation Human genes 0.000 description 1
- 102220597721 Mitochondrial basic amino acids transporter_N27H_mutation Human genes 0.000 description 1
- 102220611202 Mitochondrial import inner membrane translocase subunit Tim23B_I65M_mutation Human genes 0.000 description 1
- 102220612390 Mitogen-activated protein kinase kinase kinase 1_E10G_mutation Human genes 0.000 description 1
- 102220612495 Mitogen-activated protein kinase kinase kinase 1_T130D_mutation Human genes 0.000 description 1
- 102220535198 Mitotic checkpoint serine/threonine-protein kinase BUB1_L122G_mutation Human genes 0.000 description 1
- 102220550069 Mixed lineage kinase domain-like protein_L165G_mutation Human genes 0.000 description 1
- 102220538277 Modulator of macroautophagy TMEM150B_Y32Q_mutation Human genes 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102220501183 Multifunctional methyltransferase subunit TRM112-like protein_L9D_mutation Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 102220550234 Muscular LMNA-interacting protein_D127R_mutation Human genes 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 102220483782 Myb/SANT-like DNA-binding domain-containing protein 1_A21D_mutation Human genes 0.000 description 1
- 102220484542 Myb/SANT-like DNA-binding domain-containing protein 1_L109I_mutation Human genes 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 102220506993 Myelin protein P0_P132L_mutation Human genes 0.000 description 1
- 102220528418 Myelin protein P0_R98S_mutation Human genes 0.000 description 1
- 102220485015 Myelin proteolipid protein_A248E_mutation Human genes 0.000 description 1
- 102220485213 Myelin proteolipid protein_A39T_mutation Human genes 0.000 description 1
- 102220504085 Myeloid differentiation primary response protein MyD88_D197A_mutation Human genes 0.000 description 1
- 102220508326 Myeloid differentiation primary response protein MyD88_S209R_mutation Human genes 0.000 description 1
- 102220608094 Myosin-binding protein H_S42L_mutation Human genes 0.000 description 1
- 102220599237 Myotubularin_R69P_mutation Human genes 0.000 description 1
- 102220598996 Myotubularin_S209A_mutation Human genes 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 102220533450 N-acetylgalactosamine-6-sulfatase_Q111R_mutation Human genes 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 102220544925 N-terminal Xaa-Pro-Lys N-methyltransferase 1_D167Q_mutation Human genes 0.000 description 1
- 102220605379 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1_K110A_mutation Human genes 0.000 description 1
- 102220631011 NCK-interacting protein with SH3 domain_D14T_mutation Human genes 0.000 description 1
- 102220476547 NF-kappa-B inhibitor alpha_D35A_mutation Human genes 0.000 description 1
- 102220536793 NKG2-A/NKG2-B type II integral membrane protein_K16P_mutation Human genes 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102220525410 NPC intracellular cholesterol transporter 2_K168I_mutation Human genes 0.000 description 1
- 102220481805 Natural cytotoxicity triggering receptor 2_I218K_mutation Human genes 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
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102220574033 Neprilysin_L156S_mutation Human genes 0.000 description 1
- 102220537720 Netrin-3_K223A_mutation Human genes 0.000 description 1
- 102220515719 Neurensin-1_F40G_mutation Human genes 0.000 description 1
- 102220573812 Neuroendocrine protein 7B2_T79Y_mutation Human genes 0.000 description 1
- 102220499878 Neuronal acetylcholine receptor subunit beta-3_L118Q_mutation Human genes 0.000 description 1
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 1
- 102220606690 Neurotrimin_D23N_mutation Human genes 0.000 description 1
- 102220481793 Neutral amino acid transporter A_A164G_mutation Human genes 0.000 description 1
- 102220500341 Neutral and basic amino acid transport protein rBAT_D179Y_mutation Human genes 0.000 description 1
- 102220500403 Neutral and basic amino acid transport protein rBAT_F40V_mutation Human genes 0.000 description 1
- 102220541925 Neutrophil elastase_L47R_mutation Human genes 0.000 description 1
- 102220480979 Nicotinate phosphoribosyltransferase_I44F_mutation Human genes 0.000 description 1
- 102220480223 Nicotinate phosphoribosyltransferase_K3R_mutation Human genes 0.000 description 1
- 102220480981 Nicotinate phosphoribosyltransferase_K45G_mutation Human genes 0.000 description 1
- 102220480918 Nicotinate phosphoribosyltransferase_K45I_mutation Human genes 0.000 description 1
- 102220480917 Nicotinate phosphoribosyltransferase_K45L_mutation Human genes 0.000 description 1
- 102220480988 Nicotinate phosphoribosyltransferase_L52T_mutation Human genes 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 102220592907 Nitric oxide synthase, endothelial_N27Q_mutation Human genes 0.000 description 1
- 102220590538 Non-homologous end-joining factor 1_L139A_mutation Human genes 0.000 description 1
- 102220590514 Non-homologous end-joining factor 1_L61E_mutation Human genes 0.000 description 1
- 102220590517 Non-homologous end-joining factor 1_R64G_mutation Human genes 0.000 description 1
- 102220492970 Nuclear RNA export factor 1_L22D_mutation Human genes 0.000 description 1
- 102220520881 Nuclear autoantigenic sperm protein_L53S_mutation Human genes 0.000 description 1
- 102220558657 Nuclear protein 1_L53A_mutation Human genes 0.000 description 1
- 102220558593 Nuclear protein 1_R192A_mutation Human genes 0.000 description 1
- 102220558706 Nuclear protein 1_T68Q_mutation Human genes 0.000 description 1
- 102220609775 Nuclear protein MDM1_E11R_mutation Human genes 0.000 description 1
- 102220484383 Nuclear transcription factor Y subunit gamma_I191S_mutation Human genes 0.000 description 1
- 102220630256 Nucleic acid dioxygenase ALKBH1_I218L_mutation Human genes 0.000 description 1
- 102220630238 Nucleic acid dioxygenase ALKBH1_K182A_mutation Human genes 0.000 description 1
- 102220630191 Nucleic acid dioxygenase ALKBH1_K241A_mutation Human genes 0.000 description 1
- 102220547866 Nucleobindin-1_N140Q_mutation Human genes 0.000 description 1
- 102220547020 Nucleobindin-1_T29A_mutation Human genes 0.000 description 1
- 102220526269 Nucleophosmin_K263A_mutation Human genes 0.000 description 1
- 102220525994 NudC domain-containing protein 1_D239N_mutation Human genes 0.000 description 1
- 102220526159 NudC domain-containing protein 1_V253I_mutation Human genes 0.000 description 1
- 102220623305 O-phosphoseryl-tRNA(Sec) selenium transferase_K173M_mutation Human genes 0.000 description 1
- 102220623303 O-phosphoseryl-tRNA(Sec) selenium transferase_Q105A_mutation Human genes 0.000 description 1
- 102220488467 Olfactory receptor 10G4_V195E_mutation Human genes 0.000 description 1
- 102220558072 Olfactory receptor 2A1/2A42_Q111E_mutation Human genes 0.000 description 1
- 102220558160 Olfactory receptor 2A1/2A42_R235M_mutation Human genes 0.000 description 1
- 102220504244 Olfactory receptor 3A2_L190V_mutation Human genes 0.000 description 1
- 102220587649 Olfactory receptor 4D5_G194S_mutation Human genes 0.000 description 1
- 102220587644 Olfactory receptor 4D5_K252Q_mutation Human genes 0.000 description 1
- 102220586524 Olfactory receptor 4D5_L89I_mutation Human genes 0.000 description 1
- 102220587622 Olfactory receptor 4D5_V129L_mutation Human genes 0.000 description 1
- 102220575848 Olfactory receptor 8A1_N143C_mutation Human genes 0.000 description 1
- 102220487037 Olfactory receptor 8H3_L47I_mutation Human genes 0.000 description 1
- 102220536416 Omega-amidase NIT2_V231A_mutation Human genes 0.000 description 1
- 102220516530 Oncostatin-M_T150Q_mutation Human genes 0.000 description 1
- 102220497089 Orexin/Hypocretin receptor type 1_K3G_mutation Human genes 0.000 description 1
- 102220497087 Orexin/Hypocretin receptor type 1_K8G_mutation Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102220467304 Otoancorin_E166Q_mutation Human genes 0.000 description 1
- 102220575407 Ovarian cancer G-protein coupled receptor 1_K241Q_mutation Human genes 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102220581192 Oxidized purine nucleoside triphosphate hydrolase_V83M_mutation Human genes 0.000 description 1
- 102220541553 PDZ domain-containing protein GIPC1_F38R_mutation Human genes 0.000 description 1
- 102220479454 PH and SEC7 domain-containing protein 1_K238V_mutation Human genes 0.000 description 1
- 102220634878 PH and SEC7 domain-containing protein 3_T186P_mutation Human genes 0.000 description 1
- 102220471023 PTEN upstream open reading frame MP31_T29V_mutation Human genes 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102220493626 Paired box protein Pax-6_G18W_mutation Human genes 0.000 description 1
- 102220578116 Palladin_L232T_mutation Human genes 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102220479493 Pantetheinase_R33N_mutation Human genes 0.000 description 1
- 241000567507 Panthea Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 101710112083 Para-Rep C1 Proteins 0.000 description 1
- 101710112078 Para-Rep C2 Proteins 0.000 description 1
- 102220493735 Parkinson disease protein 7_A104T_mutation Human genes 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- 102220511855 Peptide chain release factor 1-like, mitochondrial_L177F_mutation Human genes 0.000 description 1
- 102220578099 Peptidyl-prolyl cis-trans isomerase A-like 4F_G113C_mutation Human genes 0.000 description 1
- 102220515106 Peroxisomal sarcosine oxidase_E11V_mutation Human genes 0.000 description 1
- 102220474373 Peroxisomal trans-2-enoyl-CoA reductase_E91A_mutation Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- ULECEJGNDHWSKD-QEJZJMRPSA-N Phe-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 ULECEJGNDHWSKD-QEJZJMRPSA-N 0.000 description 1
- LDSOBEJVGGVWGD-DLOVCJGASA-N Phe-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 LDSOBEJVGGVWGD-DLOVCJGASA-N 0.000 description 1
- IEIFEYBAYFSRBQ-IHRRRGAJSA-N Phe-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IEIFEYBAYFSRBQ-IHRRRGAJSA-N 0.000 description 1
- 102220636993 Phenylalanine-4-hydroxylase_A104D_mutation Human genes 0.000 description 1
- 102220617998 Phenylalanine-4-hydroxylase_D84Y_mutation Human genes 0.000 description 1
- 102220618008 Phenylalanine-4-hydroxylase_I65T_mutation Human genes 0.000 description 1
- 102220506477 Phenylalanine-tRNA ligase, mitochondrial_P77K_mutation Human genes 0.000 description 1
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
- 102220517148 Phosphate-regulating neutral endopeptidase PHEX_D84Q_mutation Human genes 0.000 description 1
- 102220493275 Phosphate-regulating neutral endopeptidase PHEX_L160R_mutation Human genes 0.000 description 1
- 102220569028 Phosphatidylcholine translocator ABCB4_A250P_mutation Human genes 0.000 description 1
- 102220498921 Phosphatidylinositol 4-phosphate 5-kinase type-1 beta_Y242H_mutation Human genes 0.000 description 1
- 102220620755 Phosphatidylserine decarboxylase proenzyme, mitochondrial_A41N_mutation Human genes 0.000 description 1
- 102220619694 Phosphoethanolamine/phosphocholine phosphatase_D203S_mutation Human genes 0.000 description 1
- 102220566612 Phospholipase A2_I191P_mutation Human genes 0.000 description 1
- 102220488580 Phosphopantothenoylcysteine decarboxylase_I78M_mutation Human genes 0.000 description 1
- 102220473261 Photoreceptor ankyrin repeat protein_L232A_mutation Human genes 0.000 description 1
- 102220630400 Piezo-type mechanosensitive ion channel component 1_D225G_mutation Human genes 0.000 description 1
- 102220497755 Pirin_A162S_mutation Human genes 0.000 description 1
- 102220620269 Pituitary-specific positive transcription factor 1_F135C_mutation Human genes 0.000 description 1
- 102220509039 Platelet-activating factor acetylhydrolase IB subunit beta_L72A_mutation Human genes 0.000 description 1
- 102220509020 Platelet-activating factor acetylhydrolase IB subunit beta_L72E_mutation Human genes 0.000 description 1
- 102220481505 Podocan_V73F_mutation Human genes 0.000 description 1
- 102220481306 Podocan_V73I_mutation Human genes 0.000 description 1
- 102220481317 Podocan_V73S_mutation Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 102220630361 Poly(A) RNA polymerase GLD2_D215A_mutation Human genes 0.000 description 1
- 102220631416 Poly(A) RNA polymerase GLD2_F163A_mutation Human genes 0.000 description 1
- 102220635375 Polyadenylate-binding protein 4-like_D5V_mutation Human genes 0.000 description 1
- 102220630068 Polypeptide N-acetylgalactosaminyltransferase 11_D197Y_mutation Human genes 0.000 description 1
- 208000020584 Polyploidy Diseases 0.000 description 1
- 102220581264 Porphobilinogen deaminase_A31P_mutation Human genes 0.000 description 1
- 102220581436 Porphobilinogen deaminase_E80G_mutation Human genes 0.000 description 1
- 102220502606 Post-GPI attachment to proteins factor 4_M260A_mutation Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102220634882 Potassium voltage-gated channel subfamily A member 3_I108A_mutation Human genes 0.000 description 1
- 102220549832 Pre-mRNA-processing factor 39_T29K_mutation Human genes 0.000 description 1
- 102220641232 Pregnancy-specific beta-1-glycoprotein 1_T43P_mutation Human genes 0.000 description 1
- 102220644293 Prelamin-A/C_T24S_mutation Human genes 0.000 description 1
- 102220630442 Presenilin-1_G206D_mutation Human genes 0.000 description 1
- 102220621923 Pro-neuropeptide Y_L22M_mutation Human genes 0.000 description 1
- 102220549201 Probable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrial_F20L_mutation Human genes 0.000 description 1
- 102220579393 Probable ATP-dependent RNA helicase DHX37_K223V_mutation Human genes 0.000 description 1
- 102220613920 Probable E3 ubiquitin-protein ligase HERC1_L107H_mutation Human genes 0.000 description 1
- 102220512977 Probable JmjC domain-containing histone demethylation protein 2C_K124G_mutation Human genes 0.000 description 1
- 102220637940 Probable cation-transporting ATPase 13A5_S96Y_mutation Human genes 0.000 description 1
- 102220535504 Probable phospholipid-transporting ATPase IIA_A217H_mutation Human genes 0.000 description 1
- 102220535503 Probable phospholipid-transporting ATPase IIA_A217R_mutation Human genes 0.000 description 1
- 102220535502 Probable phospholipid-transporting ATPase IIA_N214H_mutation Human genes 0.000 description 1
- 102220535501 Probable phospholipid-transporting ATPase IIA_N214V_mutation Human genes 0.000 description 1
- 102220543074 Probable polypeptide N-acetylgalactosaminyltransferase 8_A41E_mutation Human genes 0.000 description 1
- 102220542213 Probable polypeptide N-acetylgalactosaminyltransferase 8_S209D_mutation Human genes 0.000 description 1
- 102220482149 Probable tRNA methyltransferase 9B_K223L_mutation Human genes 0.000 description 1
- 102220547177 Profilin-3_A41R_mutation Human genes 0.000 description 1
- 102220629705 Proheparin-binding EGF-like growth factor_D71G_mutation Human genes 0.000 description 1
- 102220628909 Proheparin-binding EGF-like growth factor_E141H_mutation Human genes 0.000 description 1
- 102220636347 Proline-rich protein 27_I44L_mutation Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102220566973 Propionyl-CoA carboxylase beta chain, mitochondrial_G198D_mutation Human genes 0.000 description 1
- 102220517103 Protease-associated domain-containing protein 1_E133Q_mutation Human genes 0.000 description 1
- 102220472877 Proteasomal ATPase-associated factor 1_L89C_mutation Human genes 0.000 description 1
- 102220474046 Protection of telomeres protein 1_P222V_mutation Human genes 0.000 description 1
- 102220556890 Protein ALEX_K16V_mutation Human genes 0.000 description 1
- 102220548924 Protein Bop_L118A_mutation Human genes 0.000 description 1
- 102220480860 Protein C-ets-1_R134K_mutation Human genes 0.000 description 1
- 102220472532 Protein ENL_S117I_mutation Human genes 0.000 description 1
- 102220472531 Protein ENL_S117V_mutation Human genes 0.000 description 1
- 102220472144 Protein ENL_S234A_mutation Human genes 0.000 description 1
- 102220472528 Protein ENL_T26E_mutation Human genes 0.000 description 1
- 102220472526 Protein ENL_T26H_mutation Human genes 0.000 description 1
- 102220531990 Protein FosB_Q63N_mutation Human genes 0.000 description 1
- 102220622450 Protein Hook homolog 3_F40Y_mutation Human genes 0.000 description 1
- 102220622911 Protein Hook homolog 3_L97T_mutation Human genes 0.000 description 1
- 102220511903 Protein MTSS 1_A207C_mutation Human genes 0.000 description 1
- 102220537280 Protein NDRG2_E172S_mutation Human genes 0.000 description 1
- 102220636365 Protein PALS2_V227G_mutation Human genes 0.000 description 1
- 102220478946 Protein WFDC9_N27T_mutation Human genes 0.000 description 1
- 102220472203 Protein Wnt-2_K237M_mutation Human genes 0.000 description 1
- 102220497213 Protein Wnt-3a_S209T_mutation Human genes 0.000 description 1
- 102220543120 Protein adenylyltransferase FICD_L258D_mutation Human genes 0.000 description 1
- 102220631802 Protein amnionless_I125M_mutation Human genes 0.000 description 1
- 102220622272 Protein farnesyltransferase subunit beta_N143K_mutation Human genes 0.000 description 1
- 102220580309 Protein fem-1 homolog B_I78A_mutation Human genes 0.000 description 1
- 102220580304 Protein fem-1 homolog B_N74A_mutation Human genes 0.000 description 1
- 102220581148 Protein fem-1 homolog C_D188K_mutation Human genes 0.000 description 1
- 102220552565 Protein kinase C and casein kinase substrate in neurons protein 1_I125E_mutation Human genes 0.000 description 1
- 102220620884 Protein pitchfork_D179R_mutation Human genes 0.000 description 1
- 102220645898 Protein pitchfork_T48Y_mutation Human genes 0.000 description 1
- 102220534647 Protein quaking_I112V_mutation Human genes 0.000 description 1
- 102220534514 Protein quaking_K90S_mutation Human genes 0.000 description 1
- 102220638260 Protein rogdi homolog_K90A_mutation Human genes 0.000 description 1
- 102220468936 Protein unc-13 homolog A_E80N_mutation Human genes 0.000 description 1
- 102220522135 Protein unc-13 homolog D_I191M_mutation Human genes 0.000 description 1
- 102220643306 Protein-glutamine gamma-glutamyltransferase 2_S171E_mutation Human genes 0.000 description 1
- 102220643305 Protein-glutamine gamma-glutamyltransferase 2_W180F_mutation Human genes 0.000 description 1
- 102220643310 Protein-glutamine gamma-glutamyltransferase 2_W180L_mutation Human genes 0.000 description 1
- 102220558516 Proteinase-activated receptor 2_Y210L_mutation Human genes 0.000 description 1
- 102220515165 Protocadherin beta-7_R69D_mutation Human genes 0.000 description 1
- 102220543892 Protocadherin-10_A39I_mutation Human genes 0.000 description 1
- 102220543869 Protocadherin-10_S42G_mutation Human genes 0.000 description 1
- 102220557328 Protocadherin-19_L190R_mutation Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 102220540789 Pterin-4-alpha-carbinolamine dehydratase_Q111P_mutation Human genes 0.000 description 1
- 102220492182 Putative HERC2-like protein 3_I191E_mutation Human genes 0.000 description 1
- 102220635458 Putative POU domain, class 5, transcription factor 1B_K182T_mutation Human genes 0.000 description 1
- 102220525017 Putative T-complex protein 1 subunit theta-like 1_L122Q_mutation Human genes 0.000 description 1
- 102220549954 Putative beta-lactamase-like 1_L258M_mutation Human genes 0.000 description 1
- 102220549953 Putative beta-lactamase-like 1_T186N_mutation Human genes 0.000 description 1
- 102220501807 Putative chemokine-related protein FP248_L246W_mutation Human genes 0.000 description 1
- 102220501816 Putative chemokine-related protein FP248_S234Y_mutation Human genes 0.000 description 1
- 102220603720 Putative dispanin subfamily A member 2d_N184D_mutation Human genes 0.000 description 1
- 102220587517 Putative uncharacterized protein FLJ13197_D60G_mutation Human genes 0.000 description 1
- 102220587527 Putative uncharacterized protein FLJ13197_K81D_mutation Human genes 0.000 description 1
- 102220587526 Putative uncharacterized protein FLJ13197_N62W_mutation Human genes 0.000 description 1
- 102220565336 Putative uncharacterized protein FRMD6-AS1_I125D_mutation Human genes 0.000 description 1
- 102220589461 Putative uncharacterized protein UNQ5830/PRO19650/PRO19816_E200S_mutation Human genes 0.000 description 1
- 102220524025 Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1_E141R_mutation Human genes 0.000 description 1
- 102220524026 Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1_E80R_mutation Human genes 0.000 description 1
- 102220516968 Pyruvate dehydrogenase phosphatase regulatory subunit, mitochondrial_S171D_mutation Human genes 0.000 description 1
- 102220536096 Quinone oxidoreductase PIG3_S151V_mutation Human genes 0.000 description 1
- 102220581886 RNA N6-adenosine-methyltransferase METTL16_N184A_mutation Human genes 0.000 description 1
- 102220610256 RNA polymerase I-specific transcription initiation factor RRN3_I19L_mutation Human genes 0.000 description 1
- 102220610245 RNA polymerase I-specific transcription initiation factor RRN3_K256E_mutation Human genes 0.000 description 1
- 102220611719 RNA polymerase I-specific transcription initiation factor RRN3_R28E_mutation Human genes 0.000 description 1
- 102220530148 RNA polymerase-associated protein LEO1_S57G_mutation Human genes 0.000 description 1
- 102220626287 RUN domain-containing protein 3B_L47M_mutation Human genes 0.000 description 1
- 102220639875 Radial spoke head protein 3 homolog_S96A_mutation Human genes 0.000 description 1
- 102220639963 Radial spoke head protein 3 homolog_T186A_mutation Human genes 0.000 description 1
- 102220639962 Radial spoke head protein 3 homolog_T186D_mutation Human genes 0.000 description 1
- 102220639957 Radial spoke head protein 3 homolog_T205A_mutation Human genes 0.000 description 1
- 102220639959 Radial spoke head protein 3 homolog_T205D_mutation Human genes 0.000 description 1
- 102220547557 Ragulator complex protein LAMTOR1_E11G_mutation Human genes 0.000 description 1
- 241000232299 Ralstonia Species 0.000 description 1
- 102220509959 Ras-related C3 botulinum toxin substrate 1_V51L_mutation Human genes 0.000 description 1
- 102220509958 Ras-related C3 botulinum toxin substrate 1_V51M_mutation Human genes 0.000 description 1
- 102220510503 Ras-related C3 botulinum toxin substrate 2_P34H_mutation Human genes 0.000 description 1
- 102220510444 Ras-related C3 botulinum toxin substrate 2_T24N_mutation Human genes 0.000 description 1
- 102220615662 Ras-related protein Rab-11A_I44A_mutation Human genes 0.000 description 1
- 102220616448 Ras-related protein Rab-11A_L229I_mutation Human genes 0.000 description 1
- 102220606957 Ras-related protein Rap-1b_Q63E_mutation Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102220630934 Receptor-interacting serine/threonine-protein kinase 1_E166S_mutation Human genes 0.000 description 1
- 102220630959 Receptor-interacting serine/threonine-protein kinase 1_R161S_mutation Human genes 0.000 description 1
- 102220512936 Receptor-interacting serine/threonine-protein kinase 2_K45M_mutation Human genes 0.000 description 1
- 102220591179 Receptor-type tyrosine-protein phosphatase kappa_H82S_mutation Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102220566606 Recombining binding protein suppressor of hairless-like protein_H82A_mutation Human genes 0.000 description 1
- 206010038063 Rectal haemorrhage Diseases 0.000 description 1
- 102220576534 Regulatory solute carrier protein family 1 member 1_Q54L_mutation Human genes 0.000 description 1
- 102220615369 Remodeling and spacing factor 1_L169S_mutation Human genes 0.000 description 1
- 102220571567 Renin_E36Q_mutation Human genes 0.000 description 1
- 102220503750 Replication factor C subunit 3_T66N_mutation Human genes 0.000 description 1
- 102220492201 Replication stress response regulator SDE2_K81L_mutation Human genes 0.000 description 1
- 102220484214 Replication stress response regulator SDE2_R192G_mutation Human genes 0.000 description 1
- 102220492229 Replication stress response regulator SDE2_R37A_mutation Human genes 0.000 description 1
- 102220492283 Replication stress response regulator SDE2_R37K_mutation Human genes 0.000 description 1
- 102220483824 Replication stress response regulator SDE2_V51E_mutation Human genes 0.000 description 1
- 102220555329 Retinal-specific phospholipid-transporting ATPase ABCA4_K223Q_mutation Human genes 0.000 description 1
- 102220531765 Retinoid-inducible serine carboxypeptidase_D244N_mutation Human genes 0.000 description 1
- 102220531760 Retinoid-inducible serine carboxypeptidase_Y210H_mutation Human genes 0.000 description 1
- 241000589180 Rhizobium Species 0.000 description 1
- 241000235527 Rhizopus Species 0.000 description 1
- 102220529486 Rho guanine nucleotide exchange factor 28_R98M_mutation Human genes 0.000 description 1
- 241000316848 Rhodococcus <scale insect> Species 0.000 description 1
- 102220485672 Rhodopsin_L176M_mutation Human genes 0.000 description 1
- 102220485513 Rhodopsin_L17F_mutation Human genes 0.000 description 1
- 102220474419 Ribitol-5-phosphate xylosyltransferase 1_R69A_mutation Human genes 0.000 description 1
- 102220644564 Ribonuclease H2 subunit A_Y210A_mutation Human genes 0.000 description 1
- 102220469278 Ribosomal RNA processing protein 1 homolog B_E138R_mutation Human genes 0.000 description 1
- 102220642708 Ribosomal biogenesis protein LAS1L_F38A_mutation Human genes 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 102220466973 Runt-related transcription factor 1_I112K_mutation Human genes 0.000 description 1
- 102220592516 Runt-related transcription factor 2_T205R_mutation Human genes 0.000 description 1
- 102220517868 SCO-spondin_N259A_mutation Human genes 0.000 description 1
- 102220514467 SERTA domain-containing protein 1_L97A_mutation Human genes 0.000 description 1
- 102220611338 SPOC domain-containing protein 1_L190W_mutation Human genes 0.000 description 1
- 102220629109 STING ER exit protein_K256H_mutation Human genes 0.000 description 1
- 102220538878 SUMO-conjugating enzyme UBC9_D127S_mutation Human genes 0.000 description 1
- 241000235343 Saccharomycetales Species 0.000 description 1
- 241000187560 Saccharopolyspora Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 241000235346 Schizosaccharomyces Species 0.000 description 1
- 102220587956 Seipin_L156D_mutation Human genes 0.000 description 1
- 102220587955 Seipin_L169D_mutation Human genes 0.000 description 1
- 102220595957 Selenoprotein S_N261A_mutation Human genes 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102220601916 Sequestosome-1_R213Q_mutation Human genes 0.000 description 1
- MMGJPDWSIOAGTH-ACZMJKKPSA-N Ser-Ala-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MMGJPDWSIOAGTH-ACZMJKKPSA-N 0.000 description 1
- JAWGSPUJAXYXJA-IHRRRGAJSA-N Ser-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)N)CC1=CC=CC=C1 JAWGSPUJAXYXJA-IHRRRGAJSA-N 0.000 description 1
- 102220547916 Serine protease HTRA2, mitochondrial_A93D_mutation Human genes 0.000 description 1
- 102220578544 Serine/threonine-protein kinase 16_K81I_mutation Human genes 0.000 description 1
- 102220483931 Serine/threonine-protein kinase Chk2_T68A_mutation Human genes 0.000 description 1
- 102220498534 Serine/threonine-protein kinase N3_A155K_mutation Human genes 0.000 description 1
- 102220585332 Serine/threonine-protein kinase STK11_L160P_mutation Human genes 0.000 description 1
- 102220541489 Serine/threonine-protein kinase WNK2_K256M_mutation Human genes 0.000 description 1
- 102220504635 Serine/threonine-protein kinase receptor R3_E59V_mutation Human genes 0.000 description 1
- 102220491164 Serpin H1_A41P_mutation Human genes 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 102220585589 Short-chain dehydrogenase/reductase family 42E member 1_Q63P_mutation Human genes 0.000 description 1
- 102220563248 Signal transducer and activator of transcription 6_M181R_mutation Human genes 0.000 description 1
- 102220612903 Small EDRK-rich factor 1_Q12A_mutation Human genes 0.000 description 1
- 102220620697 Small integral membrane protein 32_M260T_mutation Human genes 0.000 description 1
- 102220523228 Sodium channel protein type 1 subunit alpha_L61F_mutation Human genes 0.000 description 1
- 102220524196 Sodium- and chloride-dependent glycine transporter 2_A162G_mutation Human genes 0.000 description 1
- 102220493359 Sodium/calcium exchanger 3_I78F_mutation Human genes 0.000 description 1
- 102220513211 Sodium/hydrogen exchanger 1_L165C_mutation Human genes 0.000 description 1
- 102220645837 Sodium/hydrogen exchanger 1_L177C_mutation Human genes 0.000 description 1
- 102220609022 Solute carrier family 15 member 1_S117N_mutation Human genes 0.000 description 1
- 102220551043 Sonic hedgehog protein_L109F_mutation Human genes 0.000 description 1
- 241000221948 Sordaria Species 0.000 description 1
- 102220524372 Sortilin-related receptor_Q148L_mutation Human genes 0.000 description 1
- 102220524375 Sortilin-related receptor_Q148P_mutation Human genes 0.000 description 1
- 102220606500 Sorting nexin-10_F40M_mutation Human genes 0.000 description 1
- 102220606457 Sorting nexin-10_L89M_mutation Human genes 0.000 description 1
- 102220606007 Sorting nexin-10_Y32S_mutation Human genes 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 102220601606 Speckle-type POZ protein_L190D_mutation Human genes 0.000 description 1
- 102220607987 Sphingolipid delta(4)-desaturase DES1_N261I_mutation Human genes 0.000 description 1
- 102220622772 Sphingomyelin phosphodiesterase_S233A_mutation Human genes 0.000 description 1
- 102220509097 Sphingosine 1-phosphate receptor 1_E146N_mutation Human genes 0.000 description 1
- 102220509417 Src-like-adapter_L229S_mutation Human genes 0.000 description 1
- 102220541320 Steroid Delta-isomerase_P222H_mutation Human genes 0.000 description 1
- 102220563227 Stonin-1_L109D_mutation Human genes 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
- 241000194024 Streptococcus salivarius Species 0.000 description 1
- 241000194020 Streptococcus thermophilus Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 102220577394 Stromal cell-derived factor 1_K45S_mutation Human genes 0.000 description 1
- 102220623070 Structural maintenance of chromosomes flexible hinge domain-containing protein 1_E136G_mutation Human genes 0.000 description 1
- 102220601835 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial_I178V_mutation Human genes 0.000 description 1
- 102220600386 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial_K90L_mutation Human genes 0.000 description 1
- 102220607204 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial_S234R_mutation Human genes 0.000 description 1
- 102220601859 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial_T152N_mutation Human genes 0.000 description 1
- 102220495862 Succinate dehydrogenase assembly factor 3, mitochondrial_D167V_mutation Human genes 0.000 description 1
- 102220610096 Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial_L122D_mutation Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102220522155 Sulfotransferase 1C4_T205P_mutation Human genes 0.000 description 1
- 102220503468 Superoxide dismutase [Cu-Zn]_D84S_mutation Human genes 0.000 description 1
- 102220538706 Superoxide dismutase [Cu-Zn]_L9Q_mutation Human genes 0.000 description 1
- 102220616453 Superoxide dismutase [Mn], mitochondrial_L9M_mutation Human genes 0.000 description 1
- 102220608462 Suppressor of cytokine signaling 3_L22F_mutation Human genes 0.000 description 1
- 102220578492 Suppressor of fused homolog_R174E_mutation Human genes 0.000 description 1
- 102220578476 Suppressor of fused homolog_S234V_mutation Human genes 0.000 description 1
- 102220565026 Survival motor neuron protein_A46N_mutation Human genes 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 102220577078 Synapsin-1_L61A_mutation Human genes 0.000 description 1
- 102220512015 Synaptotagmin-7_Q54A_mutation Human genes 0.000 description 1
- 102220606704 Syndecan-1_T29D_mutation Human genes 0.000 description 1
- 241000192584 Synechocystis Species 0.000 description 1
- 102220493237 Syntaxin-binding protein 1_T26M_mutation Human genes 0.000 description 1
- 102220521961 THAP domain-containing protein 1_A7D_mutation Human genes 0.000 description 1
- 102220521969 THAP domain-containing protein 1_K16A_mutation Human genes 0.000 description 1
- 102220521945 THAP domain-containing protein 1_L177P_mutation Human genes 0.000 description 1
- 102220521929 THAP domain-containing protein 1_L72R_mutation Human genes 0.000 description 1
- 102220538051 TIP41-like protein_D71L_mutation Human genes 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 102220500145 Target of EGR1 protein 1_N27D_mutation Human genes 0.000 description 1
- 102220548687 Tectonin beta-propeller repeat-containing protein 1_T66P_mutation Human genes 0.000 description 1
- 102220568050 Testis-specific Y-encoded protein 1_I216F_mutation Human genes 0.000 description 1
- 241000589596 Thermus Species 0.000 description 1
- 102220610852 Thialysine N-epsilon-acetyltransferase_L72G_mutation Human genes 0.000 description 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 1
- BIENEHRYNODTLP-HJGDQZAQSA-N Thr-Glu-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)O)N)O BIENEHRYNODTLP-HJGDQZAQSA-N 0.000 description 1
- MEJHFIOYJHTWMK-VOAKCMCISA-N Thr-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)[C@@H](C)O MEJHFIOYJHTWMK-VOAKCMCISA-N 0.000 description 1
- JWQNAFHCXKVZKZ-UVOCVTCTSA-N Thr-Lys-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JWQNAFHCXKVZKZ-UVOCVTCTSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102220481580 Thymocyte selection-associated high mobility group box protein TOX_T152P_mutation Human genes 0.000 description 1
- 102220617210 Tissue factor pathway inhibitor_W199R_mutation Human genes 0.000 description 1
- 102220641736 Toll-like receptor 5_N143T_mutation Human genes 0.000 description 1
- 102220468085 Trafficking protein particle complex subunit 3_L53T_mutation Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102220590230 Transcription factor 7-like 2_T212V_mutation Human genes 0.000 description 1
- 102220593206 Transcription factor GATA-4_P226Q_mutation Human genes 0.000 description 1
- 102220604981 Transcription factor Sp2_L47Q_mutation Human genes 0.000 description 1
- 102220498152 Transcriptional adapter 2-alpha_T88E_mutation Human genes 0.000 description 1
- 102220600066 Transcriptional coactivator YAP1_W199A_mutation Human genes 0.000 description 1
- 102220561788 Transcriptional repressor NF-X1_F20A_mutation Human genes 0.000 description 1
- 102220567572 Transitional endoplasmic reticulum ATPase_K256A_mutation Human genes 0.000 description 1
- 102220633953 Translation initiation factor eIF-2B subunit epsilon_V73G_mutation Human genes 0.000 description 1
- 102220498133 Transmembrane 4 L6 family member 20_F13P_mutation Human genes 0.000 description 1
- 102220495941 Transmembrane protein 185B_F13A_mutation Human genes 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 102220478538 Tropomyosin alpha-1 chain_I191N_mutation Human genes 0.000 description 1
- 102220478576 Tropomyosin alpha-1 chain_K237A_mutation Human genes 0.000 description 1
- 102220538684 Tropomyosin beta chain_D14V_mutation Human genes 0.000 description 1
- 102220483625 Troponin I, cardiac muscle_D188A_mutation Human genes 0.000 description 1
- 102220563705 Troponin T, cardiac muscle_K263R_mutation Human genes 0.000 description 1
- 102220510420 Tubulin alpha chain-like 3_G86E_mutation Human genes 0.000 description 1
- 102220586116 Tubulin polymerization-promoting protein_S159E_mutation Human genes 0.000 description 1
- 102220529070 Tudor and KH domain-containing protein_V142N_mutation Human genes 0.000 description 1
- 102220541343 Tumor necrosis factor receptor superfamily member 6_A257D_mutation Human genes 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
- 102220586067 Two pore channel protein 2_K204A_mutation Human genes 0.000 description 1
- 102220563325 Tyrosine-protein kinase BTK_R174K_mutation Human genes 0.000 description 1
- 102220563347 Tyrosine-protein kinase BTK_R28P_mutation Human genes 0.000 description 1
- 102220573512 Tyrosine-protein kinase Fer_D70K_mutation Human genes 0.000 description 1
- 102220541383 Tyrosyl-DNA phosphodiesterase 1_K238A_mutation Human genes 0.000 description 1
- 102220618248 U2 small nuclear ribonucleoprotein A'_T68K_mutation Human genes 0.000 description 1
- 102220604918 U4/U6 small nuclear ribonucleoprotein Prp4_R192E_mutation Human genes 0.000 description 1
- 102220523925 UDP-glucose 6-dehydrogenase_A104L_mutation Human genes 0.000 description 1
- 102220613237 Ubiquinone biosynthesis protein COQ9, mitochondrial_L190E_mutation Human genes 0.000 description 1
- 102220568950 Ubiquitin thioesterase OTUB2_N184Q_mutation Human genes 0.000 description 1
- 102220568941 Ubiquitin thioesterase OTUB2_T68G_mutation Human genes 0.000 description 1
- 102220606434 Ubiquitin-conjugating enzyme E2 R1_E133R_mutation Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 102220613740 Uncharacterized protein C19orf84_L160Y_mutation Human genes 0.000 description 1
- 102220571004 Uncharacterized protein C7orf57_I44N_mutation Human genes 0.000 description 1
- 102220480901 Uncharacterized protein EXOC3-AS1_V49S_mutation Human genes 0.000 description 1
- 102220555696 Urokinase plasminogen activator surface receptor_S151W_mutation Human genes 0.000 description 1
- 102220488199 Uromodulin-like 1_I78D_mutation Human genes 0.000 description 1
- 102220581281 Uroporphyrinogen-III synthase_I219S_mutation Human genes 0.000 description 1
- 102220579876 V-type proton ATPase catalytic subunit A_K256Q_mutation Human genes 0.000 description 1
- 102220476879 Vacuolar protein sorting-associated protein 16 homolog_E200R_mutation Human genes 0.000 description 1
- 102220635556 Vacuolar protein sorting-associated protein 33A_N62I_mutation Human genes 0.000 description 1
- 102220635538 Vacuolar protein sorting-associated protein 33A_N74S_mutation Human genes 0.000 description 1
- 102220475222 Vacuolar protein sorting-associated protein 33A_R64S_mutation Human genes 0.000 description 1
- 102220635199 Vacuolar protein sorting-associated protein 33A_S117T_mutation Human genes 0.000 description 1
- 102220532651 Vacuolar protein sorting-associated protein 37A_L72H_mutation Human genes 0.000 description 1
- 102220514960 Vacuolar protein sorting-associated protein 4B_A15D_mutation Human genes 0.000 description 1
- 102220514955 Vacuolar protein sorting-associated protein 4B_I58M_mutation Human genes 0.000 description 1
- 102220634008 Vacuolar protein-sorting-associated protein 36_A202R_mutation Human genes 0.000 description 1
- 102220639683 Vacuolar-sorting protein SNF8_F6E_mutation Human genes 0.000 description 1
- 102220621588 Vacuolar-sorting protein SNF8_M87E_mutation Human genes 0.000 description 1
- 102220610585 Vasoactive intestinal polypeptide receptor 1_L122A_mutation Human genes 0.000 description 1
- 102220610602 Vasoactive intestinal polypeptide receptor 1_R64E_mutation Human genes 0.000 description 1
- 102220567331 Vasopressin V2 receptor_L53R_mutation Human genes 0.000 description 1
- 102220593177 Vasopressin-neurophysin 2-copeptin_L232S_mutation Human genes 0.000 description 1
- 102220569948 Vasorin_K119E_mutation Human genes 0.000 description 1
- 102220634407 Vitamin K epoxide reductase complex subunit 1_R98K_mutation Human genes 0.000 description 1
- 102220634593 Vitamin K epoxide reductase complex subunit 1_S57A_mutation Human genes 0.000 description 1
- 102220526967 Vitamin K-dependent protein C_A240G_mutation Human genes 0.000 description 1
- 102220512314 Vitamin K-dependent protein C_G145R_mutation Human genes 0.000 description 1
- 102220469588 Voltage-dependent L-type calcium channel subunit beta-2_D60A_mutation Human genes 0.000 description 1
- 102220469587 Voltage-dependent L-type calcium channel subunit beta-2_D60K_mutation Human genes 0.000 description 1
- 102220469752 Voltage-dependent L-type calcium channel subunit beta-2_G50D_mutation Human genes 0.000 description 1
- 102220469751 Voltage-dependent L-type calcium channel subunit beta-2_G50K_mutation Human genes 0.000 description 1
- 102220470249 Voltage-dependent L-type calcium channel subunit beta-2_R28A_mutation Human genes 0.000 description 1
- 102220497191 WD repeat domain phosphoinositide-interacting protein 4_A208D_mutation Human genes 0.000 description 1
- 102220472084 Wee1-like protein kinase 2_K8T_mutation Human genes 0.000 description 1
- 102220472159 Wilms tumor protein_E116Q_mutation Human genes 0.000 description 1
- 102220555361 X-box-binding protein 1_T212N_mutation Human genes 0.000 description 1
- 241000589634 Xanthomonas Species 0.000 description 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- 102220537408 YTH domain-containing family protein 1_A103I_mutation Human genes 0.000 description 1
- 102220477462 YY1-associated factor 2_Y242A_mutation Human genes 0.000 description 1
- 102220589754 YjeF N-terminal domain-containing protein 3_G25F_mutation Human genes 0.000 description 1
- 102220589714 YjeF N-terminal domain-containing protein 3_T24Y_mutation Human genes 0.000 description 1
- 102220477119 Zinc finger protein 280A_D101E_mutation Human genes 0.000 description 1
- 102220477401 Zinc finger protein 280A_D225A_mutation Human genes 0.000 description 1
- 102220476747 Zinc finger protein 280A_G25E_mutation Human genes 0.000 description 1
- 102220482548 Zinc finger protein 543_L246H_mutation Human genes 0.000 description 1
- 102220482616 Zinc finger protein 559_T251N_mutation Human genes 0.000 description 1
- 102220637633 Zinc finger protein 600_M2V_mutation Human genes 0.000 description 1
- 102220516515 Zinc finger protein Helios_L160A_mutation Human genes 0.000 description 1
- 102220516353 Zinc finger protein Helios_R161A_mutation Human genes 0.000 description 1
- 102220515546 Zinc finger protein Helios_R183A_mutation Human genes 0.000 description 1
- 102220594693 Zinc finger protein PLAGL1_A207M_mutation Human genes 0.000 description 1
- 241000588901 Zymomonas Species 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 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
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 229940090588 amoxil Drugs 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 229940098164 augmentin Drugs 0.000 description 1
- IWLXWEWGQZEKGZ-UHFFFAOYSA-N azane;zinc Chemical compound N.[Zn] IWLXWEWGQZEKGZ-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 1
- 229940004120 bifidobacterium infantis Drugs 0.000 description 1
- 229940009291 bifidobacterium longum Drugs 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 235000020299 breve Nutrition 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 102220370481 c.101C>G Human genes 0.000 description 1
- 102220360343 c.110G>A Human genes 0.000 description 1
- 102220358890 c.116C>A Human genes 0.000 description 1
- 102200108120 c.116C>T Human genes 0.000 description 1
- 102220360497 c.124T>A Human genes 0.000 description 1
- 102220362554 c.127A>G Human genes 0.000 description 1
- 102220395130 c.128C>G Human genes 0.000 description 1
- 102220424828 c.137C>T Human genes 0.000 description 1
- 102220346311 c.139C>T Human genes 0.000 description 1
- 102220346634 c.148G>T Human genes 0.000 description 1
- 102220356489 c.148G>T Human genes 0.000 description 1
- 102220377346 c.151G>T Human genes 0.000 description 1
- 102220368360 c.157C>G Human genes 0.000 description 1
- 102220362660 c.173T>C Human genes 0.000 description 1
- 102220350264 c.175G>A Human genes 0.000 description 1
- 102220360922 c.181C>A Human genes 0.000 description 1
- 102220362998 c.182T>C Human genes 0.000 description 1
- 102220358252 c.182T>G Human genes 0.000 description 1
- 102220362973 c.18C>A Human genes 0.000 description 1
- 102220403236 c.191G>T Human genes 0.000 description 1
- 102220348242 c.205C>G Human genes 0.000 description 1
- 102220353622 c.20C>T Human genes 0.000 description 1
- 102220359783 c.234_235invCA Human genes 0.000 description 1
- 102220414510 c.236C>T Human genes 0.000 description 1
- 102220370670 c.247G>A Human genes 0.000 description 1
- 102220431755 c.247G>C Human genes 0.000 description 1
- 102220398034 c.248T>G Human genes 0.000 description 1
- 102220412485 c.263C>T Human genes 0.000 description 1
- 102220364590 c.268A>G Human genes 0.000 description 1
- 102220355138 c.268_269delAAinsGT Human genes 0.000 description 1
- 102220366004 c.26T>C Human genes 0.000 description 1
- 102220347973 c.282C>G Human genes 0.000 description 1
- 102220388270 c.283G>A Human genes 0.000 description 1
- 102220354149 c.289C>A Human genes 0.000 description 1
- 102220360285 c.292C>G Human genes 0.000 description 1
- 102220364606 c.293G>T Human genes 0.000 description 1
- 102220360476 c.302A>G Human genes 0.000 description 1
- 102220353608 c.319C>T Human genes 0.000 description 1
- 102220358419 c.323T>A Human genes 0.000 description 1
- 102220358505 c.326T>C Human genes 0.000 description 1
- 102220406079 c.330G>C Human genes 0.000 description 1
- 102220361260 c.337G>A Human genes 0.000 description 1
- 102200091490 c.340G>A Human genes 0.000 description 1
- 102220415534 c.341G>A Human genes 0.000 description 1
- 102220370510 c.344C>A Human genes 0.000 description 1
- 102220352426 c.349T>C Human genes 0.000 description 1
- 102220385349 c.350C>T Human genes 0.000 description 1
- 102220346646 c.352C>A Human genes 0.000 description 1
- 102220361158 c.352C>T Human genes 0.000 description 1
- 102220362046 c.361G>A Human genes 0.000 description 1
- 102220365114 c.364C>G Human genes 0.000 description 1
- 102200012614 c.377G>A Human genes 0.000 description 1
- 102220383647 c.377G>T Human genes 0.000 description 1
- 102220411555 c.381C>A Human genes 0.000 description 1
- 102220431382 c.388A>T Human genes 0.000 description 1
- 102220429364 c.395C>G Human genes 0.000 description 1
- 102220355826 c.406G>C Human genes 0.000 description 1
- 102220361375 c.409C>T Human genes 0.000 description 1
- 102220348556 c.410C>A Human genes 0.000 description 1
- 102220359291 c.410C>T Human genes 0.000 description 1
- 102220354971 c.415C>A Human genes 0.000 description 1
- 102220353616 c.416T>G Human genes 0.000 description 1
- 102220358597 c.424G>C Human genes 0.000 description 1
- 102220356867 c.427A>G Human genes 0.000 description 1
- 102220355795 c.428A>G Human genes 0.000 description 1
- 102220424861 c.431C>G Human genes 0.000 description 1
- 102220361180 c.434G>T Human genes 0.000 description 1
- 102220415108 c.439A>C Human genes 0.000 description 1
- 102220392647 c.446A>T Human genes 0.000 description 1
- 102220355749 c.44C>T Human genes 0.000 description 1
- 102220354217 c.451T>C Human genes 0.000 description 1
- 102220383435 c.452C>G Human genes 0.000 description 1
- 102220414532 c.452C>T Human genes 0.000 description 1
- 102220351022 c.455C>T Human genes 0.000 description 1
- 102220358034 c.457G>T Human genes 0.000 description 1
- 102220352557 c.472A>T Human genes 0.000 description 1
- 102220432497 c.473C>T Human genes 0.000 description 1
- 102220419663 c.47A>T Human genes 0.000 description 1
- 102200091175 c.481C>G Human genes 0.000 description 1
- 102220365168 c.481C>T Human genes 0.000 description 1
- 102220363558 c.488T>G Human genes 0.000 description 1
- 102220370702 c.502A>G Human genes 0.000 description 1
- 102220353289 c.508C>A Human genes 0.000 description 1
- 102220351025 c.509C>G Human genes 0.000 description 1
- 102220361255 c.512C>T Human genes 0.000 description 1
- 102220364116 c.517A>G Human genes 0.000 description 1
- 102220352408 c.523G>C Human genes 0.000 description 1
- 102220362474 c.527T>C Human genes 0.000 description 1
- 102200162311 c.52G>A Human genes 0.000 description 1
- 102220347930 c.538T>C Human genes 0.000 description 1
- 102220402998 c.53G>A Human genes 0.000 description 1
- 102220360653 c.541A>G Human genes 0.000 description 1
- 102220412356 c.542T>C Human genes 0.000 description 1
- 102220358920 c.544A>C Human genes 0.000 description 1
- 102220348627 c.548G>A Human genes 0.000 description 1
- 102200105867 c.559G>C Human genes 0.000 description 1
- 102220359796 c.55A>G Human genes 0.000 description 1
- 102220383410 c.566C>A Human genes 0.000 description 1
- 102220354944 c.581G>A Human genes 0.000 description 1
- 102220457761 c.581G>T Human genes 0.000 description 1
- 102220354461 c.592G>A Human genes 0.000 description 1
- 102220419291 c.598G>A Human genes 0.000 description 1
- 102220429076 c.604G>T Human genes 0.000 description 1
- 102220357644 c.622G>T Human genes 0.000 description 1
- 102220362473 c.626C>T Human genes 0.000 description 1
- 102220411568 c.629A>G Human genes 0.000 description 1
- 102220358038 c.638G>A Human genes 0.000 description 1
- 102220396666 c.638G>C Human genes 0.000 description 1
- 102220417835 c.646A>T Human genes 0.000 description 1
- 102220355735 c.652A>G Human genes 0.000 description 1
- 102220355091 c.660G>T Human genes 0.000 description 1
- 102220418791 c.662C>G Human genes 0.000 description 1
- 102220414676 c.670G>A Human genes 0.000 description 1
- 102220362468 c.673G>T Human genes 0.000 description 1
- 102220347709 c.689C>G Human genes 0.000 description 1
- 102220359312 c.694C>G Human genes 0.000 description 1
- 102220361721 c.701C>T Human genes 0.000 description 1
- 102220366328 c.703C>A Human genes 0.000 description 1
- 102200093315 c.704G>A Human genes 0.000 description 1
- 102220352870 c.704G>C Human genes 0.000 description 1
- 102220360076 c.707A>T Human genes 0.000 description 1
- 102200102206 c.709A>G Human genes 0.000 description 1
- 102220359207 c.711G>C Human genes 0.000 description 1
- 102220360595 c.713A>C Human genes 0.000 description 1
- 102220418142 c.714G>C Human genes 0.000 description 1
- 102220370206 c.71C>G Human genes 0.000 description 1
- 102220389194 c.727G>T Human genes 0.000 description 1
- 102220364077 c.728A>G Human genes 0.000 description 1
- 102220346603 c.729T>G Human genes 0.000 description 1
- 102220429024 c.736C>A Human genes 0.000 description 1
- 102220383332 c.737T>C Human genes 0.000 description 1
- 102220354537 c.73G>A Human genes 0.000 description 1
- 102220346567 c.73G>T Human genes 0.000 description 1
- 102220356254 c.743C>T Human genes 0.000 description 1
- 102220347887 c.749C>A Human genes 0.000 description 1
- 102220349137 c.749C>G Human genes 0.000 description 1
- 102220421585 c.760G>A Human genes 0.000 description 1
- 102220363901 c.765G>T Human genes 0.000 description 1
- 102220403293 c.773T>C Human genes 0.000 description 1
- 102200149789 c.773T>C Human genes 0.000 description 1
- 102220354364 c.785G>A Human genes 0.000 description 1
- 102220351565 c.787A>C Human genes 0.000 description 1
- 102220353762 c.799A>G Human genes 0.000 description 1
- 102220363899 c.7A>G Human genes 0.000 description 1
- 102220364486 c.8A>T Human genes 0.000 description 1
- 102200002501 c.98G>A Human genes 0.000 description 1
- 102220347737 c.98G>T Human genes 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229940041011 carbapenems Drugs 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- FLKYBGKDCCEQQM-WYUVZMMLSA-M cefazolin sodium Chemical compound [Na+].S1C(C)=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 FLKYBGKDCCEQQM-WYUVZMMLSA-M 0.000 description 1
- 229960002129 cefixime Drugs 0.000 description 1
- 229940088508 cefizox Drugs 0.000 description 1
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical compound N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 description 1
- 229960002682 cefoxitin Drugs 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 229960005090 cefpodoxime Drugs 0.000 description 1
- LTINZAODLRIQIX-FBXRGJNPSA-N cefpodoxime proxetil Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(=O)OC(C)OC(=O)OC(C)C)C(=O)C(=N/OC)\C1=CSC(N)=N1 LTINZAODLRIQIX-FBXRGJNPSA-N 0.000 description 1
- ZCCUWMICIWSJIX-NQJJCJBVSA-N ceftaroline fosamil Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OCC)C=2N=C(NP(O)(O)=O)SN=2)CC=1SC(SC=1)=NC=1C1=CC=[N+](C)C=C1 ZCCUWMICIWSJIX-NQJJCJBVSA-N 0.000 description 1
- 229960004828 ceftaroline fosamil Drugs 0.000 description 1
- 229940047496 ceftin Drugs 0.000 description 1
- 229960001991 ceftizoxime Drugs 0.000 description 1
- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 description 1
- VOAZJEPQLGBXGO-SDAWRPRTSA-N ceftobiprole Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(\C=C/4C(N([C@H]5CNCC5)CC\4)=O)CS[C@@H]32)C(O)=O)=O)=N1 VOAZJEPQLGBXGO-SDAWRPRTSA-N 0.000 description 1
- 229940099237 cefzil Drugs 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- 125000001271 cephalosporin group Chemical group 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 229960005091 chloramphenicol Drugs 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
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229940088530 claforan Drugs 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 229960003326 cloxacillin Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- SIGZQNJITOWQEF-VICXVTCVSA-M dicloxacillin sodium monohydrate Chemical compound O.[Na+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl SIGZQNJITOWQEF-VICXVTCVSA-M 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 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
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229940099739 duricef Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229940041006 first-generation cephalosporins Drugs 0.000 description 1
- 229940063190 flagyl Drugs 0.000 description 1
- 229940009273 florajen Drugs 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229960004273 floxacillin Drugs 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 229940089936 fortaz Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940114119 gentisate Drugs 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 210000005256 gram-negative cell Anatomy 0.000 description 1
- 210000005255 gram-positive cell Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 229960002182 imipenem Drugs 0.000 description 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 229940090589 keflex Drugs 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940072205 lactobacillus plantarum Drugs 0.000 description 1
- 108010030617 leucyl-phenylalanyl-valine Proteins 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 102220602238 m7GpppX diphosphatase_P170H_mutation Human genes 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940021422 maxipime Drugs 0.000 description 1
- 229940087515 mefoxin Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 229960000198 mezlocillin Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000013365 molecular weight analysis method Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 229960000515 nafcillin Drugs 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229960001019 oxacillin Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940066843 pfizerpen Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 108010024607 phenylalanylalanine Proteins 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229940104641 piperacillin / tazobactam Drugs 0.000 description 1
- 229940099765 pipracil Drugs 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940081561 rocephin Drugs 0.000 description 1
- 102220323419 rs1002894711 Human genes 0.000 description 1
- 102220221827 rs1004988362 Human genes 0.000 description 1
- 102220230405 rs1006375117 Human genes 0.000 description 1
- 102220286810 rs1034265990 Human genes 0.000 description 1
- 102220269718 rs1037879170 Human genes 0.000 description 1
- 102220235777 rs1038990717 Human genes 0.000 description 1
- 102220276006 rs1043292415 Human genes 0.000 description 1
- 102200151999 rs1044498 Human genes 0.000 description 1
- 102220297740 rs1048525846 Human genes 0.000 description 1
- 102200025065 rs104893749 Human genes 0.000 description 1
- 102200141489 rs104893788 Human genes 0.000 description 1
- 102200141491 rs104893793 Human genes 0.000 description 1
- 102200141498 rs104893793 Human genes 0.000 description 1
- 102200089573 rs104893826 Human genes 0.000 description 1
- 102220041766 rs104893826 Human genes 0.000 description 1
- 102220003030 rs104893858 Human genes 0.000 description 1
- 102200109604 rs104894003 Human genes 0.000 description 1
- 102200015929 rs104894076 Human genes 0.000 description 1
- 102200044416 rs104894256 Human genes 0.000 description 1
- 102200147946 rs104894525 Human genes 0.000 description 1
- 102200004146 rs104894575 Human genes 0.000 description 1
- 102200072128 rs104894671 Human genes 0.000 description 1
- 102200132989 rs104894729 Human genes 0.000 description 1
- 102200074455 rs104894780 Human genes 0.000 description 1
- 102200153079 rs104894818 Human genes 0.000 description 1
- 102200009646 rs104895219 Human genes 0.000 description 1
- 102220032372 rs104895229 Human genes 0.000 description 1
- 102220032371 rs104895243 Human genes 0.000 description 1
- 102220032340 rs104895312 Human genes 0.000 description 1
- 102200078012 rs104895325 Human genes 0.000 description 1
- 102220032336 rs104895325 Human genes 0.000 description 1
- 102200071317 rs1055138 Human genes 0.000 description 1
- 102220197294 rs1057519261 Human genes 0.000 description 1
- 102220198437 rs1057520006 Human genes 0.000 description 1
- 102220198799 rs1057520183 Human genes 0.000 description 1
- 102220199766 rs1057522841 Human genes 0.000 description 1
- 102220207213 rs1057524236 Human genes 0.000 description 1
- 102220211354 rs1060499755 Human genes 0.000 description 1
- 102220315951 rs1060500234 Human genes 0.000 description 1
- 102220217549 rs1060500666 Human genes 0.000 description 1
- 102220218718 rs1060500754 Human genes 0.000 description 1
- 102220215346 rs1060501163 Human genes 0.000 description 1
- 102220214161 rs1060501307 Human genes 0.000 description 1
- 102220224536 rs1060501486 Human genes 0.000 description 1
- 102220216328 rs1060501891 Human genes 0.000 description 1
- 102220218783 rs1060502044 Human genes 0.000 description 1
- 102220223279 rs1060502343 Human genes 0.000 description 1
- 102220220268 rs1060502473 Human genes 0.000 description 1
- 102220215792 rs1060502571 Human genes 0.000 description 1
- 102220215709 rs1060502610 Human genes 0.000 description 1
- 102220224869 rs1060502717 Human genes 0.000 description 1
- 102220218282 rs1060503458 Human genes 0.000 description 1
- 102220217972 rs1060503468 Human genes 0.000 description 1
- 102220214822 rs1060503549 Human genes 0.000 description 1
- 102220214800 rs1060503568 Human genes 0.000 description 1
- 102220221476 rs1060503624 Human genes 0.000 description 1
- 102220011342 rs1063385 Human genes 0.000 description 1
- 102220227884 rs1064793082 Human genes 0.000 description 1
- 102220227713 rs1064793211 Human genes 0.000 description 1
- 102220230053 rs1064793357 Human genes 0.000 description 1
- 102220227959 rs1064793625 Human genes 0.000 description 1
- 102220226106 rs1064793655 Human genes 0.000 description 1
- 102220226177 rs1064793870 Human genes 0.000 description 1
- 102220228203 rs1064793928 Human genes 0.000 description 1
- 102220230918 rs1064794245 Human genes 0.000 description 1
- 102220228799 rs1064794568 Human genes 0.000 description 1
- 102220230930 rs1064794755 Human genes 0.000 description 1
- 102220226396 rs1064794951 Human genes 0.000 description 1
- 102220227259 rs1064795189 Human genes 0.000 description 1
- 102220225518 rs1064795294 Human genes 0.000 description 1
- 102220229126 rs1064795474 Human genes 0.000 description 1
- 102220230158 rs1064795594 Human genes 0.000 description 1
- 102200105918 rs1064795841 Human genes 0.000 description 1
- 102220230387 rs1064795842 Human genes 0.000 description 1
- 102220227966 rs1064796148 Human genes 0.000 description 1
- 102220225373 rs1064796625 Human genes 0.000 description 1
- 102200102881 rs1064796681 Human genes 0.000 description 1
- 102220232846 rs1085307645 Human genes 0.000 description 1
- 102220232511 rs1085307970 Human genes 0.000 description 1
- 102220233021 rs1085307971 Human genes 0.000 description 1
- 102200074036 rs111033551 Human genes 0.000 description 1
- 102200012475 rs111033674 Human genes 0.000 description 1
- 102200012477 rs111033675 Human genes 0.000 description 1
- 102200012531 rs111033829 Human genes 0.000 description 1
- 102220026974 rs111052004 Human genes 0.000 description 1
- 102220234106 rs1114167869 Human genes 0.000 description 1
- 102200085101 rs111887056 Human genes 0.000 description 1
- 102220124510 rs112306225 Human genes 0.000 description 1
- 102220089045 rs112344257 Human genes 0.000 description 1
- 102220234639 rs1131690962 Human genes 0.000 description 1
- 102200108475 rs1131691023 Human genes 0.000 description 1
- 102200108477 rs1131691023 Human genes 0.000 description 1
- 102200103756 rs1131691025 Human genes 0.000 description 1
- 102200109051 rs1131691037 Human genes 0.000 description 1
- 102220234991 rs1131691251 Human genes 0.000 description 1
- 102220235660 rs1131691993 Human genes 0.000 description 1
- 102220283165 rs1131692078 Human genes 0.000 description 1
- 102220030906 rs113488591 Human genes 0.000 description 1
- 102220301594 rs114443105 Human genes 0.000 description 1
- 102220311282 rs114786489 Human genes 0.000 description 1
- 102220163334 rs115335100 Human genes 0.000 description 1
- 102200090276 rs11548633 Human genes 0.000 description 1
- 102220037294 rs11549840 Human genes 0.000 description 1
- 102200143559 rs11550103 Human genes 0.000 description 1
- 102200006183 rs11552822 Human genes 0.000 description 1
- 102200011729 rs115775983 Human genes 0.000 description 1
- 102220273497 rs1162974793 Human genes 0.000 description 1
- 102220042680 rs116440799 Human genes 0.000 description 1
- 102220324094 rs1166189035 Human genes 0.000 description 1
- 102220008231 rs116840773 Human genes 0.000 description 1
- 102220008240 rs116840789 Human genes 0.000 description 1
- 102220281001 rs1169190081 Human genes 0.000 description 1
- 102220082450 rs117510230 Human genes 0.000 description 1
- 102200012978 rs11757455 Human genes 0.000 description 1
- 102200062433 rs118203345 Human genes 0.000 description 1
- 102200062437 rs118203354 Human genes 0.000 description 1
- 102200059492 rs118203951 Human genes 0.000 description 1
- 102200125453 rs118203971 Human genes 0.000 description 1
- 102200075098 rs118204108 Human genes 0.000 description 1
- 102220326435 rs1190102918 Human genes 0.000 description 1
- 102220294997 rs1198543372 Human genes 0.000 description 1
- 102200004059 rs120074179 Human genes 0.000 description 1
- 102200004060 rs120074179 Human genes 0.000 description 1
- 102220327223 rs1211622922 Human genes 0.000 description 1
- 102200121302 rs12142270 Human genes 0.000 description 1
- 102200147377 rs121434280 Human genes 0.000 description 1
- 102200001998 rs121908108 Human genes 0.000 description 1
- 102200079954 rs121908978 Human genes 0.000 description 1
- 102200008028 rs121912294 Human genes 0.000 description 1
- 102200008027 rs121912306 Human genes 0.000 description 1
- 102200131573 rs121912436 Human genes 0.000 description 1
- 102200131624 rs121912440 Human genes 0.000 description 1
- 102200108472 rs121912654 Human genes 0.000 description 1
- 102200108481 rs121912654 Human genes 0.000 description 1
- 102200107958 rs121912658 Human genes 0.000 description 1
- 102200105827 rs121912665 Human genes 0.000 description 1
- 102200094891 rs121913566 Human genes 0.000 description 1
- 102200081516 rs121913589 Human genes 0.000 description 1
- 102200081522 rs121913589 Human genes 0.000 description 1
- 102200081521 rs121913590 Human genes 0.000 description 1
- 102200081460 rs121913596 Human genes 0.000 description 1
- 102220253683 rs121913596 Human genes 0.000 description 1
- 102200081304 rs121913599 Human genes 0.000 description 1
- 102200081498 rs121913604 Human genes 0.000 description 1
- 102200067182 rs121913657 Human genes 0.000 description 1
- 102200021381 rs121917755 Human genes 0.000 description 1
- 102220276493 rs121917755 Human genes 0.000 description 1
- 102200072280 rs121917953 Human genes 0.000 description 1
- 102200056787 rs121918375 Human genes 0.000 description 1
- 102200012952 rs121918641 Human genes 0.000 description 1
- 102200012954 rs121918642 Human genes 0.000 description 1
- 102220316537 rs1220477298 Human genes 0.000 description 1
- 102220277584 rs1220529268 Human genes 0.000 description 1
- 102220341303 rs1223603615 Human genes 0.000 description 1
- 102220267191 rs1245083102 Human genes 0.000 description 1
- 102220279001 rs1271849120 Human genes 0.000 description 1
- 102220281630 rs1291378382 Human genes 0.000 description 1
- 102220289851 rs1322095182 Human genes 0.000 description 1
- 102200024624 rs132630284 Human genes 0.000 description 1
- 102200024635 rs132630289 Human genes 0.000 description 1
- 102200132802 rs132630304 Human genes 0.000 description 1
- 102200097346 rs132630309 Human genes 0.000 description 1
- 102220338085 rs1340928778 Human genes 0.000 description 1
- 102220252701 rs1343618467 Human genes 0.000 description 1
- 102200063913 rs137852243 Human genes 0.000 description 1
- 102200003905 rs137852397 Human genes 0.000 description 1
- 102200095679 rs137853003 Human genes 0.000 description 1
- 102200126635 rs137853313 Human genes 0.000 description 1
- 102220010440 rs137886900 Human genes 0.000 description 1
- 102220081458 rs138048445 Human genes 0.000 description 1
- 102220020811 rs138338446 Human genes 0.000 description 1
- 102220165692 rs138592626 Human genes 0.000 description 1
- 102220257007 rs1387584638 Human genes 0.000 description 1
- 102220126492 rs139093654 Human genes 0.000 description 1
- 102200019549 rs140075817 Human genes 0.000 description 1
- 102220057412 rs141021599 Human genes 0.000 description 1
- 102220082469 rs141066870 Human genes 0.000 description 1
- 102220073966 rs141331864 Human genes 0.000 description 1
- 102220283178 rs1417452362 Human genes 0.000 description 1
- 102220212860 rs141754300 Human genes 0.000 description 1
- 102220287501 rs1417779335 Human genes 0.000 description 1
- 102220313552 rs141793230 Human genes 0.000 description 1
- 102220103687 rs141976385 Human genes 0.000 description 1
- 102220307898 rs142045411 Human genes 0.000 description 1
- 102220037461 rs142136104 Human genes 0.000 description 1
- 102220250970 rs142153571 Human genes 0.000 description 1
- 102220036885 rs142189122 Human genes 0.000 description 1
- 102220264656 rs1422655933 Human genes 0.000 description 1
- 102220266732 rs142653301 Human genes 0.000 description 1
- 102220083213 rs143417961 Human genes 0.000 description 1
- 102220237586 rs1434289035 Human genes 0.000 description 1
- 102200128606 rs143456784 Human genes 0.000 description 1
- 102220102973 rs143525924 Human genes 0.000 description 1
- 102220294825 rs144135132 Human genes 0.000 description 1
- 102220224385 rs144221071 Human genes 0.000 description 1
- 102220075238 rs144565191 Human genes 0.000 description 1
- 102220104842 rs144980336 Human genes 0.000 description 1
- 102220395357 rs145088715 Human genes 0.000 description 1
- 102220161915 rs145252200 Human genes 0.000 description 1
- 102220238128 rs145401873 Human genes 0.000 description 1
- 102220119727 rs145524909 Human genes 0.000 description 1
- 102220265043 rs1457631500 Human genes 0.000 description 1
- 102220325069 rs145773529 Human genes 0.000 description 1
- 102220253802 rs146090744 Human genes 0.000 description 1
- 102220308083 rs1462326368 Human genes 0.000 description 1
- 102200106726 rs146340390 Human genes 0.000 description 1
- 102220322897 rs146361949 Human genes 0.000 description 1
- 102220221082 rs146387899 Human genes 0.000 description 1
- 102220270377 rs146735953 Human genes 0.000 description 1
- 102220271672 rs1468589409 Human genes 0.000 description 1
- 102200102213 rs147138516 Human genes 0.000 description 1
- 102220091021 rs147984543 Human genes 0.000 description 1
- 102220180019 rs147994543 Human genes 0.000 description 1
- 102220078461 rs148304857 Human genes 0.000 description 1
- 102220282326 rs1483962771 Human genes 0.000 description 1
- 102220057261 rs148538950 Human genes 0.000 description 1
- 102220044804 rs149101834 Human genes 0.000 description 1
- 102220095974 rs149101834 Human genes 0.000 description 1
- 102220293609 rs149245876 Human genes 0.000 description 1
- 102220050226 rs149253719 Human genes 0.000 description 1
- 102220280887 rs150113270 Human genes 0.000 description 1
- 102220040905 rs150548839 Human genes 0.000 description 1
- 102220020371 rs151020603 Human genes 0.000 description 1
- 102220319392 rs151276683 Human genes 0.000 description 1
- 102220239237 rs1553156155 Human genes 0.000 description 1
- 102220313401 rs1553255479 Human genes 0.000 description 1
- 102220332829 rs1553258115 Human genes 0.000 description 1
- 102220253605 rs1553259649 Human genes 0.000 description 1
- 102200081508 rs1553259662 Human genes 0.000 description 1
- 102220247071 rs1553259811 Human genes 0.000 description 1
- 102220292874 rs1553264656 Human genes 0.000 description 1
- 102220313393 rs1553282527 Human genes 0.000 description 1
- 102220244606 rs1553323036 Human genes 0.000 description 1
- 102220249739 rs1553338193 Human genes 0.000 description 1
- 102220257006 rs1553350075 Human genes 0.000 description 1
- 102220316056 rs1553351592 Human genes 0.000 description 1
- 102220257014 rs1553351613 Human genes 0.000 description 1
- 102220257167 rs1553408119 Human genes 0.000 description 1
- 102220277218 rs1553410216 Human genes 0.000 description 1
- 102220285274 rs1553411480 Human genes 0.000 description 1
- 102220277090 rs1553411488 Human genes 0.000 description 1
- 102220284422 rs1553431702 Human genes 0.000 description 1
- 102220257798 rs1553465460 Human genes 0.000 description 1
- 102220249588 rs1553497886 Human genes 0.000 description 1
- 102220256454 rs1553506950 Human genes 0.000 description 1
- 102220257733 rs1553518141 Human genes 0.000 description 1
- 102220308025 rs1553603146 Human genes 0.000 description 1
- 102220317569 rs1553613127 Human genes 0.000 description 1
- 102220289192 rs1553619963 Human genes 0.000 description 1
- 102220316484 rs1553619979 Human genes 0.000 description 1
- 102220316977 rs1553638767 Human genes 0.000 description 1
- 102220277461 rs1553644132 Human genes 0.000 description 1
- 102220277510 rs1553644227 Human genes 0.000 description 1
- 102220285404 rs1553644231 Human genes 0.000 description 1
- 102220258954 rs1553645702 Human genes 0.000 description 1
- 102220315613 rs1553674341 Human genes 0.000 description 1
- 102220317648 rs1553902415 Human genes 0.000 description 1
- 102220278407 rs1553997389 Human genes 0.000 description 1
- 102220286546 rs1554067157 Human genes 0.000 description 1
- 102220286589 rs1554074763 Human genes 0.000 description 1
- 102220245899 rs1554247605 Human genes 0.000 description 1
- 102220297506 rs1554258798 Human genes 0.000 description 1
- 102220278760 rs1554304012 Human genes 0.000 description 1
- 102220240095 rs1554335616 Human genes 0.000 description 1
- 102220319450 rs1554378297 Human genes 0.000 description 1
- 102220243753 rs1554379882 Human genes 0.000 description 1
- 102220263496 rs1554566720 Human genes 0.000 description 1
- 102220279010 rs1554568357 Human genes 0.000 description 1
- 102220264732 rs1554654113 Human genes 0.000 description 1
- 102220263547 rs1554731003 Human genes 0.000 description 1
- 102220279253 rs1554817407 Human genes 0.000 description 1
- 102220279258 rs1554817812 Human genes 0.000 description 1
- 102220265576 rs1554825264 Human genes 0.000 description 1
- 102200088871 rs1554884979 Human genes 0.000 description 1
- 102220322695 rs1554890769 Human genes 0.000 description 1
- 102220266667 rs1554975650 Human genes 0.000 description 1
- 102220286945 rs1555059544 Human genes 0.000 description 1
- 102220266437 rs1555066315 Human genes 0.000 description 1
- 102220324017 rs1555165872 Human genes 0.000 description 1
- 102220268225 rs1555201301 Human genes 0.000 description 1
- 102220340976 rs1555207979 Human genes 0.000 description 1
- 102220267851 rs1555230056 Human genes 0.000 description 1
- 102220280446 rs1555280374 Human genes 0.000 description 1
- 102220324621 rs1555280870 Human genes 0.000 description 1
- 102220308938 rs1555361380 Human genes 0.000 description 1
- 102220325516 rs1555375788 Human genes 0.000 description 1
- 102220325488 rs1555383695 Human genes 0.000 description 1
- 102220293716 rs1555417323 Human genes 0.000 description 1
- 102220282083 rs1555461798 Human genes 0.000 description 1
- 102220270435 rs1555462056 Human genes 0.000 description 1
- 102220270659 rs1555497043 Human genes 0.000 description 1
- 102220326945 rs1555497690 Human genes 0.000 description 1
- 102220270676 rs1555497725 Human genes 0.000 description 1
- 102200105879 rs1555525921 Human genes 0.000 description 1
- 102220282507 rs1555558583 Human genes 0.000 description 1
- 102220343082 rs1555569038 Human genes 0.000 description 1
- 102220252209 rs1555574641 Human genes 0.000 description 1
- 102220287602 rs1555593593 Human genes 0.000 description 1
- 102200062089 rs1555593767 Human genes 0.000 description 1
- 102220271671 rs1555596419 Human genes 0.000 description 1
- 102220272277 rs1555599608 Human genes 0.000 description 1
- 102220245308 rs1555601006 Human genes 0.000 description 1
- 102220246768 rs1555603936 Human genes 0.000 description 1
- 102220327699 rs1555607101 Human genes 0.000 description 1
- 102220283530 rs1555609260 Human genes 0.000 description 1
- 102220271883 rs1555611550 Human genes 0.000 description 1
- 102220273265 rs1555615732 Human genes 0.000 description 1
- 102220283875 rs1555735046 Human genes 0.000 description 1
- 102220283400 rs1555737824 Human genes 0.000 description 1
- 102220274414 rs1555789213 Human genes 0.000 description 1
- 102220274355 rs1555814427 Human genes 0.000 description 1
- 102220335304 rs1555833051 Human genes 0.000 description 1
- 102220275570 rs1555864037 Human genes 0.000 description 1
- 102220116954 rs1555865401 Human genes 0.000 description 1
- 102220238271 rs1555933860 Human genes 0.000 description 1
- 102200153174 rs1555937161 Human genes 0.000 description 1
- 102200152967 rs1555937233 Human genes 0.000 description 1
- 102220290605 rs1555954685 Human genes 0.000 description 1
- 102220312275 rs1556009247 Human genes 0.000 description 1
- 102220243050 rs1556020752 Human genes 0.000 description 1
- 102220275989 rs1556435940 Human genes 0.000 description 1
- 102200131666 rs16853238 Human genes 0.000 description 1
- 102200043387 rs17876030 Human genes 0.000 description 1
- 102200164282 rs1799977 Human genes 0.000 description 1
- 102220027111 rs1799977 Human genes 0.000 description 1
- 102200032169 rs1800973 Human genes 0.000 description 1
- 102200071354 rs1801272 Human genes 0.000 description 1
- 102220036073 rs180177086 Human genes 0.000 description 1
- 102220271065 rs180177086 Human genes 0.000 description 1
- 102220282069 rs180177086 Human genes 0.000 description 1
- 102220074294 rs180177217 Human genes 0.000 description 1
- 102200039208 rs180177258 Human genes 0.000 description 1
- 102220074330 rs180177260 Human genes 0.000 description 1
- 102220217147 rs181761362 Human genes 0.000 description 1
- 102220324113 rs182282150 Human genes 0.000 description 1
- 102200000135 rs186264635 Human genes 0.000 description 1
- 102220035901 rs187864727 Human genes 0.000 description 1
- 102220037740 rs187930476 Human genes 0.000 description 1
- 102220066135 rs192628905 Human genes 0.000 description 1
- 102200079952 rs193302877 Human genes 0.000 description 1
- 102200079945 rs193302882 Human genes 0.000 description 1
- 102200079946 rs193302889 Human genes 0.000 description 1
- 102200079940 rs193302894 Human genes 0.000 description 1
- 102200080086 rs193302902 Human genes 0.000 description 1
- 102220008872 rs193921400 Human genes 0.000 description 1
- 102220008873 rs193921400 Human genes 0.000 description 1
- 102220008750 rs193922210 Human genes 0.000 description 1
- 102220008853 rs193922308 Human genes 0.000 description 1
- 102220008516 rs193922432 Human genes 0.000 description 1
- 102220009294 rs193922491 Human genes 0.000 description 1
- 102220025181 rs199469695 Human genes 0.000 description 1
- 102200004212 rs199472697 Human genes 0.000 description 1
- 102220071776 rs199472697 Human genes 0.000 description 1
- 102200004238 rs199472698 Human genes 0.000 description 1
- 102220024756 rs199472705 Human genes 0.000 description 1
- 102220024880 rs199472854 Human genes 0.000 description 1
- 102220024935 rs199473369 Human genes 0.000 description 1
- 102220088170 rs199473369 Human genes 0.000 description 1
- 102220024893 rs199473498 Human genes 0.000 description 1
- 102220024959 rs199473657 Human genes 0.000 description 1
- 102200004176 rs199473671 Human genes 0.000 description 1
- 102220034801 rs199475630 Human genes 0.000 description 1
- 102200027762 rs199475643 Human genes 0.000 description 1
- 102220034839 rs199475681 Human genes 0.000 description 1
- 102220167669 rs199515173 Human genes 0.000 description 1
- 102220123679 rs199536893 Human genes 0.000 description 1
- 102220042718 rs199651600 Human genes 0.000 description 1
- 102220198682 rs199699339 Human genes 0.000 description 1
- 102200017278 rs199768005 Human genes 0.000 description 1
- 102220044946 rs199845467 Human genes 0.000 description 1
- 102220061207 rs200048921 Human genes 0.000 description 1
- 102220087240 rs200048921 Human genes 0.000 description 1
- 102220271089 rs200048921 Human genes 0.000 description 1
- 102200148728 rs200185747 Human genes 0.000 description 1
- 102200029475 rs200313585 Human genes 0.000 description 1
- 102220056354 rs200336608 Human genes 0.000 description 1
- 102220249137 rs200418115 Human genes 0.000 description 1
- 102220054556 rs200529550 Human genes 0.000 description 1
- 102200104301 rs200579969 Human genes 0.000 description 1
- 102220197616 rs200703101 Human genes 0.000 description 1
- 102220270309 rs200756519 Human genes 0.000 description 1
- 102220074061 rs200820631 Human genes 0.000 description 1
- 102220044467 rs201141645 Human genes 0.000 description 1
- 102220247068 rs201156403 Human genes 0.000 description 1
- 102200060691 rs201258663 Human genes 0.000 description 1
- 102200114508 rs201382018 Human genes 0.000 description 1
- 102200114509 rs201382018 Human genes 0.000 description 1
- 102220456152 rs201393279 Human genes 0.000 description 1
- 102200098614 rs201431517 Human genes 0.000 description 1
- 102220058701 rs201486221 Human genes 0.000 description 1
- 102220074523 rs201622476 Human genes 0.000 description 1
- 102220233036 rs201692151 Human genes 0.000 description 1
- 102220147996 rs201710684 Human genes 0.000 description 1
- 102220313038 rs201782441 Human genes 0.000 description 1
- 102220065400 rs201820268 Human genes 0.000 description 1
- 102220259476 rs201826605 Human genes 0.000 description 1
- 102220316409 rs201834175 Human genes 0.000 description 1
- 102220176291 rs201872851 Human genes 0.000 description 1
- 102220075487 rs201956727 Human genes 0.000 description 1
- 102220111772 rs202004658 Human genes 0.000 description 1
- 102220236081 rs202058544 Human genes 0.000 description 1
- 102220288413 rs202127496 Human genes 0.000 description 1
- 102200057448 rs202194596 Human genes 0.000 description 1
- 102220285721 rs202194596 Human genes 0.000 description 1
- 102200148712 rs202247819 Human genes 0.000 description 1
- 102220011364 rs267606561 Human genes 0.000 description 1
- 102200017291 rs267606664 Human genes 0.000 description 1
- 102220002037 rs267607102 Human genes 0.000 description 1
- 102200115309 rs267607160 Human genes 0.000 description 1
- 102200027627 rs267607259 Human genes 0.000 description 1
- 102200071435 rs267607269 Human genes 0.000 description 1
- 102200131367 rs267607560 Human genes 0.000 description 1
- 102220024646 rs267607611 Human genes 0.000 description 1
- 102200164285 rs267607776 Human genes 0.000 description 1
- 102220027788 rs267607927 Human genes 0.000 description 1
- 102220026503 rs267608038 Human genes 0.000 description 1
- 102220022000 rs273901743 Human genes 0.000 description 1
- 102220019759 rs276174893 Human genes 0.000 description 1
- 102200068666 rs281865237 Human genes 0.000 description 1
- 102200076845 rs281865496 Human genes 0.000 description 1
- 102200068297 rs281875289 Human genes 0.000 description 1
- 102200068107 rs281875292 Human genes 0.000 description 1
- 102200067064 rs28897675 Human genes 0.000 description 1
- 102200028426 rs28934906 Human genes 0.000 description 1
- 102200148949 rs28936686 Human genes 0.000 description 1
- 102220056660 rs28936686 Human genes 0.000 description 1
- 102200077865 rs28936687 Human genes 0.000 description 1
- 102200087500 rs28937575 Human genes 0.000 description 1
- 102200087826 rs3212723 Human genes 0.000 description 1
- 102220005387 rs33910377 Human genes 0.000 description 1
- 102200117902 rs33910475 Human genes 0.000 description 1
- 102200117906 rs33910475 Human genes 0.000 description 1
- 102200118188 rs33913712 Human genes 0.000 description 1
- 102200118190 rs33917785 Human genes 0.000 description 1
- 102200118191 rs33917785 Human genes 0.000 description 1
- 102200071414 rs33933481 Human genes 0.000 description 1
- 102220005349 rs33933481 Human genes 0.000 description 1
- 102200118192 rs33940204 Human genes 0.000 description 1
- 102220005187 rs33941844 Human genes 0.000 description 1
- 102220005194 rs33941844 Human genes 0.000 description 1
- 102220005249 rs33941844 Human genes 0.000 description 1
- 102200082933 rs33968721 Human genes 0.000 description 1
- 102200082938 rs33968721 Human genes 0.000 description 1
- 102200118172 rs33993568 Human genes 0.000 description 1
- 102200118173 rs33993568 Human genes 0.000 description 1
- 102200135483 rs34047482 Human genes 0.000 description 1
- 102200117905 rs34240441 Human genes 0.000 description 1
- 102220005287 rs34407387 Human genes 0.000 description 1
- 102220005526 rs34410516 Human genes 0.000 description 1
- 102200092878 rs34420481 Human genes 0.000 description 1
- 102220005522 rs34472107 Human genes 0.000 description 1
- 102200118229 rs34665886 Human genes 0.000 description 1
- 102200067482 rs34817956 Human genes 0.000 description 1
- 102200092884 rs34933313 Human genes 0.000 description 1
- 102200118189 rs35002698 Human genes 0.000 description 1
- 102220005182 rs35068498 Human genes 0.000 description 1
- 102220005451 rs35317336 Human genes 0.000 description 1
- 102200118175 rs35553496 Human genes 0.000 description 1
- 102220091419 rs35765893 Human genes 0.000 description 1
- 102200118179 rs35914488 Human genes 0.000 description 1
- 102200155456 rs35947557 Human genes 0.000 description 1
- 102220005293 rs35960772 Human genes 0.000 description 1
- 102220005481 rs36024711 Human genes 0.000 description 1
- 102200118233 rs36081208 Human genes 0.000 description 1
- 102220221195 rs367797765 Human genes 0.000 description 1
- 102220237891 rs367797765 Human genes 0.000 description 1
- 102220324957 rs368645130 Human genes 0.000 description 1
- 102220323432 rs368945911 Human genes 0.000 description 1
- 102220057359 rs369120013 Human genes 0.000 description 1
- 102220118939 rs369186379 Human genes 0.000 description 1
- 102220222493 rs370082083 Human genes 0.000 description 1
- 102220324108 rs370268888 Human genes 0.000 description 1
- 102220245491 rs370404701 Human genes 0.000 description 1
- 102220235295 rs370411488 Human genes 0.000 description 1
- 102220056150 rs371142225 Human genes 0.000 description 1
- 102220114727 rs372166877 Human genes 0.000 description 1
- 102220023765 rs372321790 Human genes 0.000 description 1
- 102220013610 rs372825868 Human genes 0.000 description 1
- 102220401156 rs372844636 Human genes 0.000 description 1
- 102220058531 rs373000587 Human genes 0.000 description 1
- 102220244279 rs373241693 Human genes 0.000 description 1
- 102220097952 rs373648967 Human genes 0.000 description 1
- 102200019315 rs3737084 Human genes 0.000 description 1
- 102200076039 rs3738766 Human genes 0.000 description 1
- 102220093396 rs375336614 Human genes 0.000 description 1
- 102220238039 rs375646186 Human genes 0.000 description 1
- 102220191051 rs376230028 Human genes 0.000 description 1
- 102200078653 rs376371866 Human genes 0.000 description 1
- 102220277413 rs377430566 Human genes 0.000 description 1
- 102220273860 rs377605009 Human genes 0.000 description 1
- 102220078387 rs377724143 Human genes 0.000 description 1
- 102200027051 rs3824874 Human genes 0.000 description 1
- 102220011910 rs386134124 Human genes 0.000 description 1
- 102220028414 rs386352335 Human genes 0.000 description 1
- 102220054119 rs386789728 Human genes 0.000 description 1
- 102200049497 rs386833427 Human genes 0.000 description 1
- 102200010981 rs386833663 Human genes 0.000 description 1
- 102200022447 rs386833730 Human genes 0.000 description 1
- 102220227596 rs386834128 Human genes 0.000 description 1
- 102200017870 rs387906615 Human genes 0.000 description 1
- 102200126044 rs387907039 Human genes 0.000 description 1
- 102220023086 rs387907440 Human genes 0.000 description 1
- 102220009473 rs397507189 Human genes 0.000 description 1
- 102200067525 rs397507873 Human genes 0.000 description 1
- 102220089991 rs397507881 Human genes 0.000 description 1
- 102220020679 rs397508609 Human genes 0.000 description 1
- 102220020769 rs397508723 Human genes 0.000 description 1
- 102220020778 rs397508736 Human genes 0.000 description 1
- 102220021057 rs397508897 Human genes 0.000 description 1
- 102220021058 rs397508898 Human genes 0.000 description 1
- 102220021458 rs397509053 Human genes 0.000 description 1
- 102220021592 rs397509071 Human genes 0.000 description 1
- 102220022222 rs397509306 Human genes 0.000 description 1
- 102200150161 rs397514728 Human genes 0.000 description 1
- 102200105357 rs397516436 Human genes 0.000 description 1
- 102220013071 rs397516447 Human genes 0.000 description 1
- 102220013090 rs397516461 Human genes 0.000 description 1
- 102220013967 rs397516849 Human genes 0.000 description 1
- 102220014681 rs397517221 Human genes 0.000 description 1
- 102220016949 rs397517895 Human genes 0.000 description 1
- 102220016983 rs397517907 Human genes 0.000 description 1
- 102220288940 rs398122368 Human genes 0.000 description 1
- 102200147376 rs398123074 Human genes 0.000 description 1
- 102200030302 rs398124656 Human genes 0.000 description 1
- 102220392937 rs41273533 Human genes 0.000 description 1
- 102220019324 rs41293469 Human genes 0.000 description 1
- 102200134447 rs41295338 Human genes 0.000 description 1
- 102220159804 rs41307461 Human genes 0.000 description 1
- 102200062393 rs45517109 Human genes 0.000 description 1
- 102220036288 rs45525839 Human genes 0.000 description 1
- 102200075747 rs4685076 Human genes 0.000 description 1
- 102220039653 rs483353047 Human genes 0.000 description 1
- 102200112962 rs4904210 Human genes 0.000 description 1
- 102200089632 rs5030807 Human genes 0.000 description 1
- 102200089633 rs5030807 Human genes 0.000 description 1
- 102200091511 rs5030830 Human genes 0.000 description 1
- 102200091512 rs5030830 Human genes 0.000 description 1
- 102220269956 rs530722554 Human genes 0.000 description 1
- 102220168071 rs532180601 Human genes 0.000 description 1
- 102220074042 rs533405046 Human genes 0.000 description 1
- 102220103882 rs534158221 Human genes 0.000 description 1
- 102220059243 rs534184145 Human genes 0.000 description 1
- 102220204947 rs534473091 Human genes 0.000 description 1
- 102220159710 rs535143891 Human genes 0.000 description 1
- 102220057651 rs539285592 Human genes 0.000 description 1
- 102220283403 rs540627331 Human genes 0.000 description 1
- 102220075323 rs540745201 Human genes 0.000 description 1
- 102220223172 rs542193901 Human genes 0.000 description 1
- 102220174076 rs548909101 Human genes 0.000 description 1
- 102220324097 rs555774342 Human genes 0.000 description 1
- 102220040697 rs55755457 Human genes 0.000 description 1
- 102220142620 rs558211174 Human genes 0.000 description 1
- 102220019757 rs55854959 Human genes 0.000 description 1
- 102220288781 rs571490973 Human genes 0.000 description 1
- 102220288357 rs572035776 Human genes 0.000 description 1
- 102220024449 rs57286292 Human genes 0.000 description 1
- 102220258802 rs574777861 Human genes 0.000 description 1
- 102200053926 rs58163069 Human genes 0.000 description 1
- 102220075174 rs58528748 Human genes 0.000 description 1
- 102220047375 rs587776489 Human genes 0.000 description 1
- 102200077463 rs587777147 Human genes 0.000 description 1
- 102200075810 rs587777232 Human genes 0.000 description 1
- 102220039980 rs587778115 Human genes 0.000 description 1
- 102220097487 rs587778115 Human genes 0.000 description 1
- 102220222915 rs587778115 Human genes 0.000 description 1
- 102220040727 rs587778447 Human genes 0.000 description 1
- 102220041145 rs587778638 Human genes 0.000 description 1
- 102200105308 rs587778720 Human genes 0.000 description 1
- 102200105309 rs587778720 Human genes 0.000 description 1
- 102200105349 rs587778720 Human genes 0.000 description 1
- 102220026037 rs587778876 Human genes 0.000 description 1
- 102220027000 rs587779003 Human genes 0.000 description 1
- 102220027715 rs587779154 Human genes 0.000 description 1
- 102220257279 rs587779154 Human genes 0.000 description 1
- 102220036482 rs587779842 Human genes 0.000 description 1
- 102220036700 rs587779970 Human genes 0.000 description 1
- 102220036814 rs587780060 Human genes 0.000 description 1
- 102220037012 rs587780164 Human genes 0.000 description 1
- 102220037053 rs587780187 Human genes 0.000 description 1
- 102220041685 rs587780689 Human genes 0.000 description 1
- 102220041841 rs587780779 Human genes 0.000 description 1
- 102220041920 rs587780816 Human genes 0.000 description 1
- 102200086453 rs587780911 Human genes 0.000 description 1
- 102220044720 rs587781513 Human genes 0.000 description 1
- 102220324861 rs587781513 Human genes 0.000 description 1
- 102220198353 rs587781525 Human genes 0.000 description 1
- 102220044776 rs587781563 Human genes 0.000 description 1
- 102220044907 rs587781670 Human genes 0.000 description 1
- 102220045186 rs587781895 Human genes 0.000 description 1
- 102220045433 rs587782104 Human genes 0.000 description 1
- 102200109057 rs587782160 Human genes 0.000 description 1
- 102220045520 rs587782176 Human genes 0.000 description 1
- 102220059790 rs587782176 Human genes 0.000 description 1
- 102220045819 rs587782411 Human genes 0.000 description 1
- 102200108188 rs587782423 Human genes 0.000 description 1
- 102220045989 rs587782546 Human genes 0.000 description 1
- 102220046285 rs587782804 Human genes 0.000 description 1
- 102220330649 rs587782813 Human genes 0.000 description 1
- 102220047659 rs587783138 Human genes 0.000 description 1
- 102220048830 rs587783741 Human genes 0.000 description 1
- 102200132794 rs587783796 Human genes 0.000 description 1
- 102220049946 rs587783796 Human genes 0.000 description 1
- 102200132812 rs587783836 Human genes 0.000 description 1
- 102200132778 rs587783848 Human genes 0.000 description 1
- 102200132775 rs587783850 Human genes 0.000 description 1
- 102200131520 rs58917027 Human genes 0.000 description 1
- 102220087848 rs58917027 Human genes 0.000 description 1
- 102200081810 rs5952410 Human genes 0.000 description 1
- 102200131344 rs59914820 Human genes 0.000 description 1
- 102200076409 rs60551555 Human genes 0.000 description 1
- 102200004679 rs61540016 Human genes 0.000 description 1
- 102200028427 rs61748411 Human genes 0.000 description 1
- 102200110496 rs61748530 Human genes 0.000 description 1
- 102220078415 rs61750441 Human genes 0.000 description 1
- 102200100804 rs61751277 Human genes 0.000 description 1
- 102200047049 rs61753163 Human genes 0.000 description 1
- 102220033243 rs61753173 Human genes 0.000 description 1
- 102200028554 rs61754421 Human genes 0.000 description 1
- 102220206132 rs61755047 Human genes 0.000 description 1
- 102220046737 rs61755760 Human genes 0.000 description 1
- 102220046818 rs63485860 Human genes 0.000 description 1
- 102200027528 rs63749936 Human genes 0.000 description 1
- 102200163542 rs63749994 Human genes 0.000 description 1
- 102220032618 rs63750082 Human genes 0.000 description 1
- 102220215401 rs63750085 Human genes 0.000 description 1
- 102220026637 rs63750098 Human genes 0.000 description 1
- 102200027519 rs63750255 Human genes 0.000 description 1
- 102220005506 rs63750467 Human genes 0.000 description 1
- 102200163563 rs63750648 Human genes 0.000 description 1
- 102200163547 rs63750706 Human genes 0.000 description 1
- 102220027108 rs63750706 Human genes 0.000 description 1
- 102220104430 rs63750821 Human genes 0.000 description 1
- 102200058169 rs63750907 Human genes 0.000 description 1
- 102220257305 rs63750913 Human genes 0.000 description 1
- 102220276879 rs63750913 Human genes 0.000 description 1
- 102220005476 rs63750950 Human genes 0.000 description 1
- 102220027732 rs63751040 Human genes 0.000 description 1
- 102200164344 rs63751661 Human genes 0.000 description 1
- 102220316828 rs63751661 Human genes 0.000 description 1
- 102200148399 rs672601366 Human genes 0.000 description 1
- 102220032082 rs67890094 Human genes 0.000 description 1
- 102200101903 rs72556259 Human genes 0.000 description 1
- 102220032073 rs72556261 Human genes 0.000 description 1
- 102220032083 rs72556268 Human genes 0.000 description 1
- 102200101662 rs72558416 Human genes 0.000 description 1
- 102220032115 rs72558424 Human genes 0.000 description 1
- 102220051104 rs727503347 Human genes 0.000 description 1
- 102220054254 rs727503499 Human genes 0.000 description 1
- 102220055109 rs727503935 Human genes 0.000 description 1
- 102220051010 rs727504245 Human genes 0.000 description 1
- 102220054396 rs727504591 Human genes 0.000 description 1
- 102220256604 rs73003124 Human genes 0.000 description 1
- 102220056393 rs730880039 Human genes 0.000 description 1
- 102220056210 rs730880065 Human genes 0.000 description 1
- 102220056149 rs730880232 Human genes 0.000 description 1
- 102220057201 rs730880397 Human genes 0.000 description 1
- 102220057214 rs730880408 Human genes 0.000 description 1
- 102220056935 rs730880464 Human genes 0.000 description 1
- 102220056648 rs730881059 Human genes 0.000 description 1
- 102220056644 rs730881062 Human genes 0.000 description 1
- 102220057295 rs730881073 Human genes 0.000 description 1
- 102200115281 rs730881163 Human genes 0.000 description 1
- 102220058400 rs730881695 Human genes 0.000 description 1
- 102220057450 rs730881811 Human genes 0.000 description 1
- 102220057451 rs730881811 Human genes 0.000 description 1
- 102220286181 rs730881811 Human genes 0.000 description 1
- 102220057679 rs730881861 Human genes 0.000 description 1
- 102200091177 rs730882035 Human genes 0.000 description 1
- 102220058441 rs730882127 Human genes 0.000 description 1
- 102220243370 rs730882127 Human genes 0.000 description 1
- 102220249585 rs745528957 Human genes 0.000 description 1
- 102220102435 rs745802492 Human genes 0.000 description 1
- 102220058914 rs746259256 Human genes 0.000 description 1
- 102220263662 rs746487281 Human genes 0.000 description 1
- 102220247730 rs746913146 Human genes 0.000 description 1
- 102220158453 rs747515126 Human genes 0.000 description 1
- 102220252563 rs747522089 Human genes 0.000 description 1
- 102220279085 rs747536732 Human genes 0.000 description 1
- 102220261303 rs747727711 Human genes 0.000 description 1
- 102220267366 rs748554882 Human genes 0.000 description 1
- 102220062433 rs748636216 Human genes 0.000 description 1
- 102220224466 rs748636216 Human genes 0.000 description 1
- 102220237415 rs748654930 Human genes 0.000 description 1
- 102220250587 rs748964205 Human genes 0.000 description 1
- 102220093316 rs749037674 Human genes 0.000 description 1
- 102220094427 rs749037674 Human genes 0.000 description 1
- 102220226502 rs749671520 Human genes 0.000 description 1
- 102200087919 rs749780769 Human genes 0.000 description 1
- 102220242548 rs750080180 Human genes 0.000 description 1
- 102220267142 rs750386693 Human genes 0.000 description 1
- 102220216166 rs750821213 Human genes 0.000 description 1
- 102220270280 rs750928338 Human genes 0.000 description 1
- 102220064637 rs750955319 Human genes 0.000 description 1
- 102200027760 rs75193786 Human genes 0.000 description 1
- 102200027761 rs75193786 Human genes 0.000 description 1
- 102220149644 rs752540751 Human genes 0.000 description 1
- 102220149517 rs752723849 Human genes 0.000 description 1
- 102220285380 rs752793866 Human genes 0.000 description 1
- 102220272204 rs753085009 Human genes 0.000 description 1
- 102220324299 rs753101641 Human genes 0.000 description 1
- 102220323131 rs753389706 Human genes 0.000 description 1
- 102220330076 rs753472058 Human genes 0.000 description 1
- 102220188063 rs753646145 Human genes 0.000 description 1
- 102220095360 rs754033733 Human genes 0.000 description 1
- 102200121588 rs754036398 Human genes 0.000 description 1
- 102220266379 rs754283907 Human genes 0.000 description 1
- 102220214707 rs754478179 Human genes 0.000 description 1
- 102220317291 rs754699919 Human genes 0.000 description 1
- 102220196873 rs755382547 Human genes 0.000 description 1
- 102220271085 rs756856792 Human genes 0.000 description 1
- 102220277494 rs758040210 Human genes 0.000 description 1
- 102220287908 rs758642067 Human genes 0.000 description 1
- 102220285402 rs758802692 Human genes 0.000 description 1
- 102220316349 rs759171890 Human genes 0.000 description 1
- 102220330781 rs759734429 Human genes 0.000 description 1
- 102220212669 rs759829161 Human genes 0.000 description 1
- 102220067289 rs761359362 Human genes 0.000 description 1
- 102220216205 rs761954026 Human genes 0.000 description 1
- 102220316268 rs762400168 Human genes 0.000 description 1
- 102220264454 rs762630679 Human genes 0.000 description 1
- 102220102929 rs762648754 Human genes 0.000 description 1
- 102220080892 rs762874073 Human genes 0.000 description 1
- 102220098936 rs763547482 Human genes 0.000 description 1
- 102220140231 rs764125735 Human genes 0.000 description 1
- 102220198342 rs764146326 Human genes 0.000 description 1
- 102220198349 rs764146326 Human genes 0.000 description 1
- 102220214871 rs764149433 Human genes 0.000 description 1
- 102220318009 rs764280416 Human genes 0.000 description 1
- 102220223523 rs764312409 Human genes 0.000 description 1
- 102220274487 rs764641221 Human genes 0.000 description 1
- 102220315544 rs764764823 Human genes 0.000 description 1
- 102220185333 rs765090704 Human genes 0.000 description 1
- 102220267891 rs765898876 Human genes 0.000 description 1
- 102220242265 rs765921870 Human genes 0.000 description 1
- 102220139542 rs765931092 Human genes 0.000 description 1
- 102220268380 rs766131342 Human genes 0.000 description 1
- 102220086575 rs766203500 Human genes 0.000 description 1
- 102220254294 rs766907690 Human genes 0.000 description 1
- 102220285557 rs767157505 Human genes 0.000 description 1
- 102220058931 rs767371843 Human genes 0.000 description 1
- 102220194786 rs767371843 Human genes 0.000 description 1
- 102200114115 rs767564684 Human genes 0.000 description 1
- 102220258442 rs767581059 Human genes 0.000 description 1
- 102220226395 rs767780451 Human genes 0.000 description 1
- 102220326201 rs768526036 Human genes 0.000 description 1
- 102220330850 rs768542145 Human genes 0.000 description 1
- 102220261694 rs768911543 Human genes 0.000 description 1
- 102220214341 rs769061878 Human genes 0.000 description 1
- 102200067148 rs769650474 Human genes 0.000 description 1
- 102220104792 rs769882912 Human genes 0.000 description 1
- 102200115480 rs76992529 Human genes 0.000 description 1
- 102220231914 rs770020244 Human genes 0.000 description 1
- 102220224231 rs770503805 Human genes 0.000 description 1
- 102220245078 rs771011731 Human genes 0.000 description 1
- 102200057225 rs771170000 Human genes 0.000 description 1
- 102220227468 rs771300829 Human genes 0.000 description 1
- 102220222910 rs771332058 Human genes 0.000 description 1
- 102220205737 rs771543236 Human genes 0.000 description 1
- 102220215245 rs771612764 Human genes 0.000 description 1
- 102220246476 rs772347588 Human genes 0.000 description 1
- 102220069971 rs773503933 Human genes 0.000 description 1
- 102220216713 rs773580818 Human genes 0.000 description 1
- 102220251947 rs773916549 Human genes 0.000 description 1
- 102220084102 rs773998134 Human genes 0.000 description 1
- 102220213091 rs774237159 Human genes 0.000 description 1
- 102220095999 rs774521832 Human genes 0.000 description 1
- 102220227720 rs775217949 Human genes 0.000 description 1
- 102220264024 rs776810966 Human genes 0.000 description 1
- 102220251723 rs776827432 Human genes 0.000 description 1
- 102220323207 rs777016570 Human genes 0.000 description 1
- 102220128569 rs777178486 Human genes 0.000 description 1
- 102220245898 rs777266582 Human genes 0.000 description 1
- 102220280607 rs777373591 Human genes 0.000 description 1
- 102220219601 rs777689913 Human genes 0.000 description 1
- 102220095092 rs777845808 Human genes 0.000 description 1
- 102220316816 rs777965976 Human genes 0.000 description 1
- 102220141930 rs778259023 Human genes 0.000 description 1
- 102220215248 rs778528329 Human genes 0.000 description 1
- 102220240379 rs780178733 Human genes 0.000 description 1
- 102220273022 rs780581573 Human genes 0.000 description 1
- 102220292648 rs780774076 Human genes 0.000 description 1
- 102220340038 rs782167890 Human genes 0.000 description 1
- 102220266138 rs782308530 Human genes 0.000 description 1
- 102200009423 rs78408272 Human genes 0.000 description 1
- 102220330013 rs78488639 Human genes 0.000 description 1
- 102220059857 rs786201252 Human genes 0.000 description 1
- 102220198398 rs786201419 Human genes 0.000 description 1
- 102220059035 rs786201910 Human genes 0.000 description 1
- 102220062241 rs786201968 Human genes 0.000 description 1
- 102220062242 rs786201968 Human genes 0.000 description 1
- 102220316041 rs786202335 Human genes 0.000 description 1
- 102220061993 rs786202533 Human genes 0.000 description 1
- 102220061705 rs786202993 Human genes 0.000 description 1
- 102220058942 rs786203108 Human genes 0.000 description 1
- 102220058894 rs786203226 Human genes 0.000 description 1
- 102220062461 rs786203283 Human genes 0.000 description 1
- 102220061992 rs786203319 Human genes 0.000 description 1
- 102220061202 rs786203440 Human genes 0.000 description 1
- 102220061417 rs786203607 Human genes 0.000 description 1
- 102220062554 rs786204153 Human genes 0.000 description 1
- 102220062805 rs786204222 Human genes 0.000 description 1
- 102220064548 rs786205494 Human genes 0.000 description 1
- 102200007405 rs794727239 Human genes 0.000 description 1
- 102200121587 rs794727484 Human genes 0.000 description 1
- 102220069100 rs794727615 Human genes 0.000 description 1
- 102220069311 rs794727654 Human genes 0.000 description 1
- 102220069943 rs794727777 Human genes 0.000 description 1
- 102220072097 rs794728201 Human genes 0.000 description 1
- 102220070991 rs794728711 Human genes 0.000 description 1
- 102220072442 rs794728978 Human genes 0.000 description 1
- 102220075990 rs796052481 Human genes 0.000 description 1
- 102220076551 rs796052528 Human genes 0.000 description 1
- 102220076765 rs796052619 Human genes 0.000 description 1
- 102220074729 rs796053206 Human genes 0.000 description 1
- 102220075553 rs796053359 Human genes 0.000 description 1
- 102220077423 rs797044950 Human genes 0.000 description 1
- 102200018967 rs79761867 Human genes 0.000 description 1
- 102220319678 rs79761867 Human genes 0.000 description 1
- 102200147926 rs80338704 Human genes 0.000 description 1
- 102200040544 rs80356525 Human genes 0.000 description 1
- 102220009454 rs80356863 Human genes 0.000 description 1
- 102220028143 rs80356864 Human genes 0.000 description 1
- 102220020965 rs80356883 Human genes 0.000 description 1
- 102220009472 rs80357084 Human genes 0.000 description 1
- 102220028139 rs80357084 Human genes 0.000 description 1
- 102200067143 rs80357438 Human genes 0.000 description 1
- 102200058482 rs80358202 Human genes 0.000 description 1
- 102200083967 rs80358210 Human genes 0.000 description 1
- 102220019141 rs80358660 Human genes 0.000 description 1
- 102220019199 rs80358691 Human genes 0.000 description 1
- 102220019329 rs80358747 Human genes 0.000 description 1
- 102220019742 rs80358956 Human genes 0.000 description 1
- 102220096029 rs80358956 Human genes 0.000 description 1
- 102200067655 rs80358961 Human genes 0.000 description 1
- 102220019752 rs80358962 Human genes 0.000 description 1
- 102220005617 rs80359822 Human genes 0.000 description 1
- 102220081831 rs863223983 Human genes 0.000 description 1
- 102200152969 rs863224471 Human genes 0.000 description 1
- 102220083649 rs863224573 Human genes 0.000 description 1
- 102220083467 rs863224774 Human genes 0.000 description 1
- 102220084260 rs863224855 Human genes 0.000 description 1
- 102220084370 rs863224907 Human genes 0.000 description 1
- 102220084710 rs863225120 Human genes 0.000 description 1
- 102220085804 rs864321637 Human genes 0.000 description 1
- 102200102904 rs864622115 Human genes 0.000 description 1
- 102220087254 rs864622284 Human genes 0.000 description 1
- 102200091488 rs869025636 Human genes 0.000 description 1
- 102220090326 rs869069617 Human genes 0.000 description 1
- 102220089254 rs869312808 Human genes 0.000 description 1
- 102220090408 rs876657989 Human genes 0.000 description 1
- 102220096730 rs876658359 Human genes 0.000 description 1
- 102220095190 rs876658581 Human genes 0.000 description 1
- 102220095943 rs876659107 Human genes 0.000 description 1
- 102220094426 rs876659274 Human genes 0.000 description 1
- 102220097494 rs876659315 Human genes 0.000 description 1
- 102220095237 rs876659353 Human genes 0.000 description 1
- 102220097491 rs876659614 Human genes 0.000 description 1
- 102220094219 rs876659637 Human genes 0.000 description 1
- 102220095374 rs876659832 Human genes 0.000 description 1
- 102220096878 rs876659849 Human genes 0.000 description 1
- 102220285791 rs876660173 Human genes 0.000 description 1
- 102220095063 rs876660196 Human genes 0.000 description 1
- 102220095998 rs876660440 Human genes 0.000 description 1
- 102220094084 rs876660490 Human genes 0.000 description 1
- 102220097528 rs876660641 Human genes 0.000 description 1
- 102220094411 rs876660926 Human genes 0.000 description 1
- 102220093431 rs876661010 Human genes 0.000 description 1
- 102220093681 rs876661079 Human genes 0.000 description 1
- 102200153173 rs876661119 Human genes 0.000 description 1
- 102220093558 rs876661210 Human genes 0.000 description 1
- 102220093421 rs876661239 Human genes 0.000 description 1
- 102220093170 rs876661257 Human genes 0.000 description 1
- 102220098054 rs876661376 Human genes 0.000 description 1
- 102220099580 rs878853748 Human genes 0.000 description 1
- 102220099568 rs878853751 Human genes 0.000 description 1
- 102220103815 rs878853956 Human genes 0.000 description 1
- 102220100740 rs878854050 Human genes 0.000 description 1
- 102220100724 rs878854056 Human genes 0.000 description 1
- 102220098981 rs878854155 Human genes 0.000 description 1
- 102220103616 rs878854701 Human genes 0.000 description 1
- 102220103944 rs878854923 Human genes 0.000 description 1
- 102220103151 rs878854946 Human genes 0.000 description 1
- 102220105566 rs879254627 Human genes 0.000 description 1
- 102200121015 rs879255632 Human genes 0.000 description 1
- 102220267843 rs879762286 Human genes 0.000 description 1
- 102220089103 rs886037806 Human genes 0.000 description 1
- 102220285718 rs886037806 Human genes 0.000 description 1
- 102220114396 rs886039195 Human genes 0.000 description 1
- 102220115424 rs886039513 Human genes 0.000 description 1
- 102220118474 rs886042066 Human genes 0.000 description 1
- 102220121960 rs886042965 Human genes 0.000 description 1
- 102220122509 rs886043109 Human genes 0.000 description 1
- 102220123508 rs886043429 Human genes 0.000 description 1
- 102220125666 rs886044042 Human genes 0.000 description 1
- 102220125918 rs886044113 Human genes 0.000 description 1
- 102220226059 rs886044113 Human genes 0.000 description 1
- 102220126814 rs886044376 Human genes 0.000 description 1
- 102220175451 rs886049644 Human genes 0.000 description 1
- 102220430129 rs886051892 Human genes 0.000 description 1
- 102220186141 rs886053030 Human genes 0.000 description 1
- 102220133422 rs886054767 Human genes 0.000 description 1
- 102220145201 rs886059686 Human genes 0.000 description 1
- 102220155715 rs886062788 Human genes 0.000 description 1
- 102220324277 rs889470853 Human genes 0.000 description 1
- 102220318824 rs904474688 Human genes 0.000 description 1
- 102220313220 rs915794675 Human genes 0.000 description 1
- 102220329489 rs923000484 Human genes 0.000 description 1
- 102200160773 rs934996 Human genes 0.000 description 1
- 102220328780 rs947488726 Human genes 0.000 description 1
- 102220270665 rs955754399 Human genes 0.000 description 1
- 102220214799 rs963501454 Human genes 0.000 description 1
- 102220278116 rs977002306 Human genes 0.000 description 1
- 102220290163 rs978623916 Human genes 0.000 description 1
- 102220276450 rs978988174 Human genes 0.000 description 1
- 102220287825 rs990737815 Human genes 0.000 description 1
- 102220284165 rs999812302 Human genes 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000002579 sigmoidoscopy Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 229940082787 spirulina Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229940072226 suprax Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 102220482183 tRNA pseudouridine synthase A_E11S_mutation Human genes 0.000 description 1
- 102220482685 tRNA pseudouridine synthase A_P226A_mutation Human genes 0.000 description 1
- 102220532864 tRNA wybutosine-synthesizing protein 3 homolog_I58Q_mutation Human genes 0.000 description 1
- 102220532847 tRNA wybutosine-synthesizing protein 3 homolog_K8L_mutation Human genes 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 101150032575 tcdA gene Proteins 0.000 description 1
- 101150089436 tcdB gene Proteins 0.000 description 1
- 229960001114 temocillin Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- KTAVBOYXMBQFGR-MAODNAKNSA-J tetrasodium;(6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-1-oxidoethylidene]amino]-3-[(2-methyl-5,6-dioxo-1h-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C KTAVBOYXMBQFGR-MAODNAKNSA-J 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940054969 vantin Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 102220503108 von Hippel-Lindau disease tumor suppressor_G114C_mutation Human genes 0.000 description 1
- 102220503201 von Hippel-Lindau disease tumor suppressor_N131T_mutation Human genes 0.000 description 1
- 102220503018 von Hippel-Lindau disease tumor suppressor_R161P_mutation Human genes 0.000 description 1
- 102220588469 von Willebrand factor A domain-containing protein 5B1_S96D_mutation Human genes 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- C12N9/86—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides, e.g. penicillinase (3.5.2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/02—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amides (3.5.2)
- C12Y305/02006—Beta-lactamase (3.5.2.6)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
本出願は、2014年4月17日に出願された米国特許仮出願第61/980,844号、および2014年9月5日に出願された米国特許仮出願第62/046,627号の利益を主張する。これら両仮出願は、参照によりその全体が本明細書に組み込まれる。
発明の分野
配列番号:1
Glu Met Lys Asp Asp Phe Ala Lys Leu Glu Glu Gln Phe Asp Ala Lys Leu Gly Ile Phe Ala Leu Asp Thr Gly Thr Asn Arg Thr Val Ala Tyr Arg Pro Asp Glu Arg Phe Ala Phe Ala Ser Thr Ile Lys Ala Leu Thr Val Gly Val Leu Leu Gln Gln Lys Ser Ile Glu Asp Leu Asn Gln Arg Ile Thr Tyr Thr Arg Asp Asp Leu Val Asn Tyr Asn Pro Ile Thr Glu Lys His Val Asp Thr Gly Met Thr Leu Lys Glu Leu Ala Asp Ala Ser Leu Arg Tyr Ser Asp Asn Ala Ala Gln Asn Leu Ile Leu Lys Gln Ile Gly Gly Pro Glu Ser Leu Lys Lys Glu Leu Arg Lys Ile Gly Asp Glu Val Thr Asn Pro Glu Arg Phe Glu Pro Glu Leu Asn Glu Val Asn Pro Gly Glu Thr Gln Asp Thr Ser Thr Ala Arg Ala Leu Val Thr Ser Leu Arg Ala Phe Ala Leu Glu Asp Lys Leu Pro Ser Glu Lys Arg Glu Leu Leu Ile Asp Trp Met Lys Arg Asn Thr Thr Gly Asp Ala Leu Ile Arg Ala Gly Val Pro Asp Gly Trp Glu Val Ala Asp Lys Thr Gly Ala Ala Ser Tyr Gly Thr Arg Asn Asp Ile Ala Ile Ile Trp Pro Pro Lys Gly Asp Pro Val Val Leu Ala Val Leu Ser Ser Arg Asp Lys Lys Asp Ala Lys Tyr Asp Asp Lys Leu Ile Ala Glu Ala Thr Lys Val Val Met Lys Ala Leu Asn Met Asn Gly Lys.
配列番号:3
Met Ile Gln Lys Arg Lys Arg Thr Val Ser Phe Arg Leu Val Leu Met Cys Thr Leu Leu Phe Val Ser Leu Pro Ile Thr Lys Thr Ser Ala Gln Ala Ser Lys Thr Glu Met Lys Asp Asp Phe Ala Lys Leu Glu Glu Gln Phe Asp Ala Lys Leu Gly Ile Phe Ala Leu Asp Thr Gly Thr Asn Arg Thr Val Ala Tyr Arg Pro Asp Glu Arg Phe Ala Phe Ala Ser Thr Ile Lys Ala Leu Thr Val Gly Val Leu Leu Gln Gln Lys Ser Ile Glu Asp Leu Asn Gln Arg Ile Thr Tyr Thr Arg Asp Asp Leu Val Asn Tyr Asn Pro Ile Thr Glu Lys His Val Asp Thr Gly Met Thr Leu Lys Glu Leu Ala Asp Ala Ser Leu Arg Tyr Ser Asp Asn Ala Ala Gln Asn Leu Ile Leu Lys Gln Ile Gly Gly Pro Glu Ser Leu Lys Lys Glu Leu Arg Lys Ile Gly Asp Glu Val Thr Asn Pro Glu Arg Phe Glu Pro Glu Leu Asn Glu Val Asn Pro Gly Glu Thr Gln Asp Thr Ser Thr Ala Arg Ala Leu Val Thr Ser Leu Arg Ala Phe Ala Leu Glu Asp Lys Leu Pro Ser Glu Lys Arg Glu Leu Leu Ile Asp Trp Met Lys Arg Asn Thr Thr Gly Asp Ala Leu Ile Arg Ala Gly Val Pro Asp Gly Trp Glu Val Ala Asp Lys Thr Gly Ala Ala Ser Tyr Gly Thr Arg Asn Asp Ile Ala Ile Ile Trp Pro Pro Lys Gly Asp Pro Val Val Leu Ala Val Leu Ser Ser Arg Asp Lys Lys Asp Ala Lys Tyr Asp Asp Lys Leu Ile Ala Glu Ala Thr Lys Val Val Met Lys Ala Leu Asn Met Asn Gly Lys
配列番号:2
gagatgaaagatgattttgcaaaacttgaggaacaatttgatgcaaaactcgggatctttgcattggatacaggtacaaaccggacggtagcgtatcggccggatgagcgttttgcttttgcttcgacgattaaggctttaactgtaggcgtgcttttgcaacagaaatcaatagaagatctgaaccagagaataacatatacacgtgatgatcttgtaaactacaacccgattacggaaaagcacgttgatacgggaatgacgctcaaagagcttgcggatgcttcgcttcgatatagtgacaatgcggcacagaatctcattcttaaacaaattggcggacctgaaagtttgaaaaaggaactgaggaagattggtgatgaggttacaaatcccgaacgattcgaaccagagttaaatgaagtgaatccgggtgaaactcaggataccagtacagcaagagcacttgtcacaagccttcgagcctttgctcttgaagataaacttccaagtgaaaaacgcgagcttttaatcgattggatgaaacgaaataccactggagacgccttaatccgtgccggtgtgccggacggttgggaagtggctgataaaactggagcggcatcatatggaacccggaatgacattgccatcatttggccgccaaaaggagatcctgtcgttcttgcagtattatccagcagggataaaaaggacgccaagtatgatgataaacttattgcagaggcaacaaaggtggtaatgaaagccttaaacatgaacggcaaataa
配列番号:4
atgattcaaaaacgaaagcggacagtttcgttcagacttgtgcttatgtgcacgctgttatttgtcagtttgccgattacaaaaacatcagcgcaagcttccaagacggagatgaaagatgattttgcaaaacttgaggaacaatttgatgcaaaactcgggatctttgcattggatacaggtacaaaccggacggtagcgtatcggccggatgagcgttttgcttttgcttcgacgattaaggctttaactgtaggcgtgcttttgcaacagaaatcaatagaagatctgaaccagagaataacatatacacgtgatgatcttgtaaactacaacccgattacggaaaagcacgttgatacgggaatgacgctcaaagagcttgcggatgcttcgcttcgatatagtgacaatgcggcacagaatctcattcttaaacaaattggcggacctgaaagtttgaaaaaggaactgaggaagattggtgatgaggttacaaatcccgaacgattcgaaccagagttaaatgaagtgaatccgggtgaaactcaggataccagtacagcaagagcacttgtcacaagccttcgagcctttgctcttgaagataaacttccaagtgaaaaacgcgagcttttaatcgattggatgaaacgaaataccactggagacgccttaatccgtgccggtgtgccggacggttgggaagtggctgataaaactggagcggcatcatatggaacccggaatgacattgccatcatttggccgccaaaaggagatcctgtcgttcttgcagtattatccagcagggataaaaaggacgccaagtatgatgataaacttattgcagaggcaacaaaggtggtaatgaaagccttaaacatgaacggcaaataa
Glu1Ala; Glu1Cys; Glu1Asp; Glu1Phe; Glu1Gly; Glu1His; Glu1Ile; Met1Lys; Glu1Leu; Glu1Met; Glu1Asn; Glu1Pro; Glu1Gln; Glu1Arg; Glu1Ser; Glu1Thr; Glu1Val; Glu1Trp; Glu1Tyr; Met2Ala; Met2Cys; Met2Asp; Met2Glu; Met2Phe; Met2Gly; Met2His; Met2Ile; Met1Lys; Met2Leu; Met2Asn; Met2Pro; Met2Gln; Met2Arg; Met2Ser; Met2Thr; Met2Val; Met2Trp; Met2Tyr; Lys3Ala; Lys3Cys; Lys3Asp; Lys3Glu; Lys3Phe; Lys3Gly; Lys3His; Lys3Ile; Lys3Leu; Lys3Met; Lys3Asn; Lys3Pro; Lys3Gln; Lys3Arg; Lys3Ser; Lys3Thr; Lys3Val; Lys3Trp; Lys3Tyr; Asp4Ala; Asp4Cys; Asp4Glu; Asp4Phe; Asp4Gly; Asp4His; Asp4Ile; Asp4Lys; Asp4Leu; Asp4Met; Asp4Asn; Asp4Pro; Asp4Gln; Asp4Arg; Asp4Ser; Asp4Thr; Asp4Val; Asp4Trp; Asp4Tyr; Asp5Ala; Asp5Cys; Asp5Glu; Asp5Phe; Asp5Gly; Asp5His; Asp5Ile; Asp5Lys; Asp5Leu; Asp5Met; Asp5Asn; Asp5Pro; Asp5Gln; Asp5Arg; Asp5Ser; Asp5Thr; Asp5Val; Asp5Trp; Asp5Tyr; Phe6Ala; Phe6Cys; Phe6Asp; Phe6Glu; Phe6Gly; Phe6His; Phe6Ile; Phe6Lys; Phe6Leu; Phe6Met; Phe6Asn; Phe6Pro; Phe6Gln; Phe6Arg; Phe6Ser; Phe6Thr; Phe6Val; Phe6Trp; Phe6Tyr; Ala7Cys; Ala7Asp; Ala7Glu; Ala7Phe; Ala7Gly; Ala7His; Ala7Ile; Ala7Lys; Ala7Leu; Ala7Met; Ala7Asn; Ala7Pro; Ala7Gln; Ala7Arg; Ala7Ser; Ala7Thr; Ala7Val; Ala7Trp; Ala7Tyr; Lys8Ala; Lys8Cys; Lys8Asp; Lys8Glu; Lys8Phe; Lys8Gly; Lys8His; Lys8Ile; Lys8Leu; Lys8Met; Lys8Asn; Lys8Pro; Lys8Gln; Lys8Arg; Lys8Ser; Lys8Thr; Lys8Val; Lys8Trp; Lys8Tyr; Leu9Ala; Leu9Cys; Leu9Asp; Leu9Glu; Leu9Phe; Leu9Gly; Leu9His; Leu9Ile; Leu9Lys; Leu9Met; Leu9Asn; Leu9Pro; Leu9Gln; Leu9Arg; Leu9Ser; Leu9Thr; Leu9Val; Leu9Trp; Leu9Tyr; Glu10Ala; Glu10Cys; Glu10Asp; Glu10Phe; Glu10Gly; Glu10His; Glu10Ile; Glu10Lys; Glu10Leu; Glu10Met; Glu10Asn; Glu10Pro; Glu10Gln; Glu10Arg; Glu10Ser; Glu10Thr; Glu10Val; Glu10Trp; Glu10Tyr; Glu11Ala; Glu11Cys; Glu11Asp; Glu11Phe; Glu11Gly; Glu11His; Glu11Ile; Glu11Lys; Glu11Leu; Glu11Met; Glu11Asn; Glu11Pro; Glu11Gln; Glu11Arg; Glu11Ser; Glu11Thr; Glu11Val; Glu11Trp; Glu11Tyr; Gln12Ala; Gln12Cys; Gln12Asp; Gln12Glu; Gln12Phe; Gln12Gly; Gln12His; Gln12Ile; Gln12Lys; Gln12Leu; Gln12Met; Gln12Asn; Gln12Pro; Gln12Arg; Gln12Ser; Gln12Thr; Gln12Val; Gln12Trp; Gln12Tyr; Phe13Ala; Phe13Cys; Phe13Asp; Phe13Glu; Phe13Gly; Phe13His; Phe13Ile; Phe13Lys; Phe13Leu; Phe13Met; Phe13Asn; Phe13Pro; Phe13Gln; Phe13Arg; Phe13Ser; Phe13Thr; Phe13Val; Phe13Trp; Phe13Tyr; Asp14Ala; Asp14Cys; Asp14Glu; Asp14Phe; Asp14Gly; Asp14His; Asp14Ile; Asp14Lys; Asp14Leu; Asp14Met; Asp14Asn; Asp14Pro; Asp14Gln; Asp14Arg; Asp14Ser; Asp14Thr; Asp14Val; Asp14Trp; Asp14Tyr; Ala15Cys; Ala15Asp; Ala15Glu; Ala15Phe; Ala15Gly; Ala15His; Ala15Ile; Ala15Lys; Ala15Leu; Ala15Met; Ala15Asn; Ala15Pro; Ala15Gln; Ala15Arg; Ala15Ser; Ala15Thr; Ala15Val; Ala15Trp; Ala15Tyr; Lys16Ala; Lys16Cys; Lys16Asp; Lys16Glu; Lys16Phe; Lys16Gly; Lys16His; Lys16Ile; Lys16Leu; Lys16Met; Lys16Asn; Lys16Pro; Lys16Gln; Lys16Arg; Lys16Ser; Lys16Thr; Lys16Val; Lys16Trp; Lys16Tyr; Leu17Ala; Leu17Cys; Leu17Asp; Leu17Glu; Leu17Phe; Leu17Gly; Leu17His; Leu17Ile; Leu17Lys; Leu17Met; Leu17Asn; Leu17Pro; Leu17Gln; Leu17Arg; Leu17Ser; Leu17Thr; Leu17Val; Leu17Trp; Leu17Tyr; Gly18Ala; Gly18Cys; Gly18Asp; Gly18Glu; Gly18Phe; Gly18His; Gly18Ile; Gly18Lys; Gly18Leu; Gly18Met; Gly18Asn; Gly18Pro; Gly18Gln; Gly18Arg; Gly18Ser; Gly18Thr; Gly18Val; Gly18Trp; Gly18Tyr; Ile19Ala; Ile19Cys; Ile19Asp; Ile19Glu; Ile19Phe; Ile19Gly; Ile19His; Ile19Lys; Ile19Leu; Ile19Met; Ile19Asn; Ile19Pro; Ile19Gln; Ile19Arg; Ile19Ser; Ile19Thr; Ile19Val; Ile19Trp; Ile19Tyr; Phe20Ala; Phe20Cys; Phe20Asp; Phe20Glu; Phe20Gly; Phe20His; Phe20Ile; Phe20Lys; Phe20Leu; Phe20Met; Phe20Asn; Phe20Pro; Phe20Gln; Phe20Arg; Phe20Ser; Phe20Thr; Phe20Val; Phe20Trp; Phe20Tyr; Ala21Cys; Ala21Asp; Ala21Glu; Ala21Phe; Ala21Gly; Ala21His; Ala21Ile; Ala21Lys; Ala21Leu; Ala21Met; Ala21Asn; Ala21Pro; Ala21Gln; Ala21Arg; Ala21Ser; Ala21Thr; Ala21Val; Ala21Trp; Ala21Tyr; Leu22Ala; Leu22Cys; Leu22Asp; Leu22Glu; Leu22Phe; Leu22Gly; Leu22His; Leu22Ile; Leu22Lys; Leu22Met; Leu22Asn; Leu22Pro; Leu22Gln; Leu22Arg; Leu22Ser; Leu22Thr; Leu22Val; Leu22Trp; Leu22Tyr; Asp23Ala; Asp23Cys; Asp23Glu; Asp23Phe; Asp23Gly; Asp23His; Asp23Ile; Asp23Lys; Asp23Leu; Asp23Met; Asp23Asn; Asp23Pro; Asp23Gln; Asp23Arg; Asp23Ser; Asp23Thr; Asp23Val; Asp23Trp; Asp23Tyr; Thr24Ala; Thr24Cys; Thr24Asp; Thr24Glu; Thr24Phe; Thr24Gly; Thr24His; Thr24Ile; Thr24Lys; Thr24Leu; Thr24Met; Thr24Asn; Thr24Pro; Thr24Gln; Thr24Arg; Thr24Ser; Thr24Val; Thr24Trp; Thr24Tyr; Gly25Ala; Gly25Cys; Gly25Asp; Gly25Glu; Gly25Phe; Gly25His; Gly25Ile; Gly25Lys; Gly25Leu; Gly25Met; Gly25Asn; Gly25Pro; Gly25Gln; Gly25Arg; Gly25Ser; Gly25Thr; Gly25Val; Gly25Trp; Gly25Tyr; Thr26Ala; Thr26Cys; Thr26Asp; Thr26Glu; Thr26Phe; Thr26Gly; Thr26His; Thr26Ile; Thr26Lys; Thr26Leu; Thr26Met; Thr26Asn; Thr26Pro; Thr26Gln; Thr26Arg; Thr26Ser; Thr26Val; Thr26Trp; Thr26Tyr; Asn27Ala; Asn27Cys; Asn27Asp; Asn27Glu; Asn27Phe; Asn27Gly; Asn27His; Asn27Ile; Asn27Lys; Asn27Leu; Asn27Met; Asn27Pro; Asn27Gln; Asn27Arg; Asn27Ser; Asn27Thr; Asn27Val; Asn27Trp; Asn27Tyr; Arg28Ala; Arg28Cys; Arg28Asp; Arg28Glu; Arg28Phe; Arg28Gly; Arg28His; Arg28Ile; Arg28Lys; Arg28Leu; Arg28Met; Arg28Asn; Arg28Pro; Arg28Gln; Arg28Ser; Arg28Thr; Ar
g28Val; Arg28Trp; Arg28Tyr; Thr29Ala; Thr29Cys; Thr29Asp; Thr29Glu; Thr29Phe; Thr29Gly; Thr29His; Thr29Ile; Thr29Lys; Thr29Leu; Thr29Met; Thr29Asn; Thr29Pro; Thr29Gln; Thr29Arg; Thr29Ser; Thr29Val; Thr29Trp; Thr29Tyr; Val30Ala; Val30Cys; Val30Asp; Val30Glu; Val30Phe; Val30Gly; Val30His; Val30Ile; Val30Lys; Val30Leu; Val30Met; Val30Asn; Val30Pro; Val30Gln; Val30Arg; Val30Ser; Val30Thr; Val30Trp; Val30Tyr; Ala31Ala; Ala31Cys; Ala31Asp; Ala31Glu; Ala31Phe; Ala31Gly; Ala31His; Ala31Ile; Ala31Lys; Ala31Leu; Ala31Met; Ala31Asn; Ala31Pro; Ala31Gln; Ala31Arg; Ala31Ser; Ala31Thr; Ala31Val; Ala31Trp; Ala31Tyr; Tyr32Ala; Tyr32Cys; Tyr32Asp; Tyr32Glu; Tyr32Phe; Tyr32Gly; Tyr32His; Tyr32Ile; Tyr32Lys; Tyr32Leu; Tyr32Met; Tyr32Asn; Tyr32Pro; Tyr32Gln; Tyr32Arg; Tyr32Ser; Tyr32Thr; Tyr32Val; Tyr32Trp; Arg33Ala; Arg33Cys; Arg33Asp; Arg33Glu; Arg33Phe; Arg33Gly; Arg33His; Arg33Ile; Arg33Lys; Arg33Leu; Arg33Met; Arg33Asn; Arg33Pro; Arg33Gln; Arg33Ser; Arg33Thr; Arg33Val; Arg33Trp; Arg33Tyr; Pro34Ala; Pro34Cys; Pro34Asp; Pro34Glu; Pro34Phe; Pro34Gly; Pro34His; Pro34Ile; Pro34Lys; Pro34Leu; Pro34Met; Pro34Asn; Pro34Gln; Pro34Arg; Pro34Ser; Pro34Thr; Pro34Val; Pro34Trp; Pro34Tyr; Asp35Ala; Asp35Cys; Asp35Glu; Asp35Phe; Asp35Gly; Asp35His; Asp35Ile; Asp35Lys; Asp35Leu; Asp35Met; Asp35Asn; Asp35Pro; Asp35Gln; Asp35Arg; Asp35Ser; Asp35Thr; Asp35Val; Asp35Trp; Asp35Tyr; Glu36Ala; Glu36Cys; Glu36Asp; Glu36Phe; Glu36Gly; Glu36His; Glu36Ile; Glu36Lys; Glu36Leu; Glu36Met; Glu36Asn; Glu36Pro; Glu36Gln; Glu36Arg; Glu36Ser; Glu36Thr; Glu36Val; Glu36Trp; Glu36Tyr; Arg37Ala; Arg37Cys; Arg37Asp; Arg37Glu; Arg37Phe; Arg37Gly; Arg37His; Arg37Ile; Arg37Lys; Arg37Leu; Arg37Met; Arg37Asn; Arg37Pro; Arg37Gln; Arg37Ser; Arg37Thr; Arg37Val; Arg37Trp; Arg37Tyr; Phe38Ala; Phe38Cys; Phe38Asp; Phe38Glu; Phe38Gly; Phe38His; Phe38Ile; Phe38Lys; Phe38Leu; Phe38Met; Phe38Asn; Phe38Pro; Phe38Gln; Phe38Arg; Phe38Ser; Phe38Thr; Phe38Val; Phe38Trp; Phe38Tyr; Ala39Cys; Ala39Asp; Ala39Glu; Ala39Phe; Ala39Gly; Ala39His; Ala39Ile; Ala39Lys; Ala39Leu; Ala39Met; Ala39Asn; Ala39Pro; Ala39Gln; Ala39Arg; Ala39Ser; Ala39Thr; Ala39Val; Ala39Trp; Ala39Tyr; Phe40Ala; Phe40Cys; Phe40Asp; Phe40Glu; Phe40Gly; Phe40His; Phe40Ile; Phe40Lys; Phe40Leu; Phe40Met; Phe40Asn; Phe40Pro; Phe40Gln; Phe40Arg; Phe40Ser; Phe40Thr; Phe40Val; Phe40Trp; Phe40Tyr; Ala41Cys; Ala41Asp; Ala41Glu; Ala41Phe; Ala41Gly; Ala41His; Ala41Ile; Ala41Lys; Ala41Leu; Ala41Met; Ala41Asn; Ala41Pro; Ala41Gln; Ala41Arg; Ala41Ser; Ala41Thr; Ala41Val; Ala41Trp; Ala41Tyr; Ser42Ala; Ser42Cys; Ser42Asp; Ser42Glu; Ser42Phe; Ser42Gly; Ser42His; Ser42Ile; Ser42Lys; Ser42Leu; Ser42Met; Ser42Asn; Ser42Pro; Ser42Gln; Ser42Arg; Ser42Thr; Ser42Val; Ser42Trp; Ser42Tyr; Thr43Ala; Thr43Cys; Thr43Asp; Thr43Glu; Thr43Phe; Thr43Gly; Thr43His; Thr43Ile; Thr43Lys; Thr43Leu; Thr43Met; Thr43Asn; Thr43Pro; Thr43Gln; Thr43Arg; Thr43Ser; Thr43Val; Thr43Trp; Thr43Tyr; Ile44Ala; Ile44Cys; Ile44Asp; Ile44Glu; Ile44Phe; Ile44Gly; Ile44His; Ile44Lys; Ile44Leu; Ile44Met; Ile44Asn; Ile44Pro; Ile44Gln; Ile44Arg; Ile44Ser; Ile44Thr; Ile44Val; Ile44Trp; Ile44Tyr; Lys45Ala; Lys45Cys; Lys45Asp; Lys45Glu; Lys45Phe; Lys45Gly; Lys45His; Lys45Ile; Lys45Leu; Lys45Met; Lys45Asn; Lys45Pro; Lys45Gln; Lys45Arg; Lys45Ser; Lys45Thr; Lys45Val; Lys45Trp; Lys45Tyr; Ala46Cys; Ala46Asp; Ala46Glu; Ala46Phe; Ala46Gly; Ala46His; Ala46Ile; Ala46Lys; Ala46Leu; Ala46Met; Ala46Asn; Ala46Pro; Ala46Gln; Ala46Arg; Ala46Ser; Ala46Thr; Ala46Val; Ala46Trp; Ala46Tyr; Leu47Ala; Leu47Cys; Leu47Asp; Leu47Glu; Leu47Phe; Leu47Gly; Leu47His; Leu47Ile; Leu47Lys; Leu47Met; Leu47Asn; Leu47Pro; Leu47Gln; Leu47Arg; Leu47Ser; Leu47Thr; Leu47Val; Leu47Trp; Leu47Tyr; Thr48Ala; Thr48Cys; Thr48Asp; Thr48Glu; Thr48Phe; Thr48Gly; Thr48His; Thr48Ile; Thr48Lys; Thr48Leu; Thr48Met; Thr48Asn; Thr48Pro; Thr48Gln; Thr48Arg; Thr48Ser; Thr48Val; Thr48Trp; Thr48Tyr; Val49Ala; Val49Cys; Val49Asp; Val49Glu; Val49Phe; Val49Gly; Val49His; Val49Ile; Val49Lys; Val49Leu; Val49Met; Val49Asn; Val49Pro; Val49Gln; Val49Arg; Val49Ser; Val49Thr; Val49Trp; Val49Tyr; Gly50Ala; Gly50Cys; Gly50Asp; Gly50Glu; Gly50Phe; Gly50His; Gly50Ile; Gly50Lys; Gly50Leu; Gly50Met; Gly50Asn; Gly50Pro; Gly50Gln; Gly50Arg; Gly50Ser; Gly50Thr; Gly50Val; Gly50Trp; Gly50Tyr; Val51Ala; Val51Cys; Val51Asp; Val51Glu; Val51Phe; Val51Gly; Val51His; Val51Ile; Val51Lys; Val51Leu; Val51Met; Val51Asn; Val51Pro; Val51Gln; Val51Arg; Val51Ser; Val51Thr; Val51Trp; Val51Tyr; Leu52Ala; Leu52Cys; Leu52Asp; Leu52Glu; Leu52Phe; Leu52Gly; Leu52His; Leu52Ile; Leu52Lys; Leu52Met; Leu52Asn; Leu52Pro; Leu52Gln; Leu52Arg; Leu52Ser; Leu52Thr; Leu52Val; Leu52Trp; Leu52Tyr; Leu53Ala; Leu53Cys; Leu53Asp; Leu53Glu; Leu53Phe; Leu53Gly; Leu53His; Leu53Ile; Leu53Lys; Leu53Met; Leu53Asn; Leu53Pro; Leu53Gln; Leu53Arg; Leu53Ser; Leu53Thr; Leu53Val; Leu53Trp; Leu53Tyr; Gln54Ala; Gln54Cys; Gln54Asp; Gln54Glu; Gln54Phe; Gln54Gly; Gln54His; Gln54Ile; Gln54Lys; Gln54Leu; Gln54Met; Gln54Asn; Gln54Pro; Gln54Arg; Gln54Ser; Gln54Thr; Gln54Val; Gln54Trp; Gln54Tyr; Gln55Ala; Gln55Cys; Gln55Asp; Gln55Glu; Gln55Phe; Gln55Gly; Gln55His; Gln55Ile; Gln55Lys; Gln55Leu; Gln55Met; Gln55Asn; Gln55Pro; Gln55Arg; Gln
55Ser; Gln55Thr; Gln55Val; Gln55Trp; Gln55Tyr; Lys56Ala; Lys56Cys; Lys56Asp; Lys56Glu; Lys56Phe; Lys56Gly; Lys56His; Lys56Ile; Lys56Leu; Lys56Met; Lys56Asn; Lys56Pro; Lys56Gln; Lys56Arg; Lys56Ser; Lys56Thr; Lys56Val; Lys56Trp; Lys56Tyr; Ser57Ala; Ser57Cys; Ser57Asp; Ser57Glu; Ser57Phe; Ser57Gly; Ser57His; Ser57Ile; Ser57Lys; Ser57Leu; Ser57Met; Ser57Asn; Ser57Pro; Ser57Gln; Ser57Arg; Ser57Thr; Ser57Val; Ser57Trp; Ser57Tyr; Ile58Ala; Ile58Cys; Ile58Asp; Ile58Glu; Ile58Phe; Ile58Gly; Ile58His; Ile58Lys; Ile58Leu; Ile58Met; Ile58Asn; Ile58Pro; Ile58Gln; Ile58Arg; Ile58Ser; Ile58Thr; Ile58Val; Ile58Trp; Ile58Tyr; Glu59Ala; Glu59Cys; Glu59Asp; Glu59Phe; Glu59Gly; Glu59His; Glu59Ile; Glu59Lys; Glu59Leu; Glu59Met; Glu59Asn; Glu59Pro; Glu59Gln; Glu59Arg; Glu59Ser; Glu59Thr; Glu59Val; Glu59Trp; Glu59Tyr; Asp60Ala; Asp60Cys; Asp60Glu; Asp60Phe; Asp60Gly; Asp60His; Asp60Ile; Asp60Lys; Asp60Leu; Asp60Met; Asp60Asn; Asp60Pro; Asp60Gln; Asp60Arg; Asp60Ser; Asp60Thr; Asp60Val; Asp60Trp; Asp60Tyr; Leu61Ala; Leu61Cys; Leu61Asp; Leu61Glu; Leu61Phe; Leu61Gly; Leu61His; Leu61Ile; Leu61Lys; Leu61Met; Leu61Asn; Leu61Pro; Leu61Gln; Leu61Arg; Leu61Ser; Leu61Thr; Leu61Val; Leu61Trp; Leu61Tyr; Asn62Ala; Asn62Cys; Asn62Asp; Asn62Glu; Asn62Phe; Asn62Gly; Asn62His; Asn62Ile; Asn62Lys; Asn62Leu; Asn62Met; Asn62Pro; Asn62Gln; Asn62Arg; Asn62Ser; Asn62Thr; Asn62Val; Asn62Trp; Asn62Tyr; Gln63Ala; Gln63Cys; Gln63Asp; Gln63Glu; Gln63Phe; Gln63Gly; Gln63His; Gln63Ile; Gln63Lys; Gln63Leu; Gln63Met; Gln63Asn; Gln63Pro; Gln63Arg; Gln63Ser; Gln63Thr; Gln63Val; Gln63Trp; Gln63Tyr; Arg64Ala; Arg64Cys; Arg64Asp; Arg64Glu; Arg64Phe; Arg64Gly; Arg64His; Arg64Ile; Arg64Lys; Arg64Leu; Arg64Met; Arg64Asn; Arg64Pro; Arg64Gln; Arg64Ser; Arg64Thr; Arg64Val; Arg64Trp; Arg64Tyr; Ile65Ala; Ile65Cys; Ile65Asp; Ile65Glu; Ile65Phe; Ile65Gly; Ile65His; Ile65Lys; Ile65Leu; Ile65Met; Ile65Asn; Ile65Pro; Ile65Gln; Ile65Arg; Ile65Ser; Ile65Thr; Ile65Val; Ile65Trp; Ile65Tyr; Thr66Ala; Thr66Cys; Thr66Asp; Thr66Glu; Thr66Phe; Thr66Gly; Thr66His; Thr66Ile; Thr66Lys; Thr66Leu; Thr66Met; Thr66Asn; Thr66Pro; Thr66Gln; Thr66Arg; Thr66Ser; Thr66Val; Thr66Trp; Thr66Tyr; Tyr67Ala; Tyr67Cys; Tyr67Asp; Tyr67Glu; Tyr67Phe; Tyr67Gly; Tyr67His; Tyr67Ile; Tyr67Lys; Tyr67Leu; Tyr67Met; Tyr67Asn; Tyr67Pro; Tyr67Gln; Tyr67Arg; Tyr67Ser; Tyr67Thr; Tyr67Val; Tyr67Trp; Thr68Ala; Thr68Cys; Thr68Asp; Thr68Glu; Thr68Phe; Thr68Gly; Thr68His; Thr68Ile; Thr68Lys; Thr68Leu; Thr68Met; Thr68Asn; Thr68Pro; Thr68Gln; Thr68Arg; Thr68Ser; Thr68Val; Thr68Trp; Thr68Tyr; Arg69Ala; Arg69Cys; Arg69Asp; Arg69Glu; Arg69Phe; Arg69Gly; Arg69His; Arg69Ile; Arg69Lys; Arg69Leu; Arg69Met; Arg69Asn; Arg69Pro; Arg69Gln; Arg69Ser; Arg69Thr; Arg69Val; Arg69Trp; Arg69Tyr; Asp70Ala; Asp70Cys; Asp70Glu; Asp70Phe; Asp70Gly; Asp70His; Asp70Ile; Asp70Lys; Asp70Leu; Asp70Met; Asp70Asn; Asp70Pro; Asp70Gln; Asp70Arg; Asp70Ser; Asp70Thr; Asp70Val; Asp70Trp; Asp70Tyr; Asp71Ala; Asp71Cys; Asp71Glu; Asp71Phe; Asp71Gly; Asp71His; Asp71Ile; Asp71Lys; Asp71Leu; Asp71Met; Asp71Asn; Asp71Pro; Asp71Gln; Asp71Arg; Asp71Ser; Asp71Thr; Asp71Val; Asp71Trp; Asp71Tyr; Leu72Ala; Leu72Cys; Leu72Asp; Leu72Glu; Leu72Phe; Leu72Gly; Leu72His; Leu72Ile; Leu72Lys; Leu72Met; Leu72Asn; Leu72Pro; Leu72Gln; Leu72Arg; Leu72Ser; Leu72Thr; Leu72Val; Leu72Trp; Leu72Tyr; Val73Ala; Val73Cys; Val73Asp; Val73Glu; Val73Phe; Val73Gly; Val73His; Val73Ile; Val73Lys; Val73Leu; Val73Met; Val73Asn; Val73Pro; Val73Gln; Val73Arg; Val73Ser; Val73Thr; Val73Trp; Val73Tyr; Asn74Ala; Asn74Cys; Asn74Asp; Asn74Glu; Asn74Phe; Asn74Gly; Asn74His; Asn74Ile; Asn74Lys; Asn74Leu; Asn74Met; Asn74Pro; Asn74Gln; Asn74Arg; Asn74Ser; Asn74Thr; Asn74Val; Asn74Trp; Asn74Tyr; Tyr75Ala; Tyr75Cys; Tyr75Asp; Tyr75Glu; Tyr75Phe; Tyr75Gly; Tyr75His; Tyr75Ile; Tyr75Lys; Tyr75Leu; Tyr75Met; Tyr75Asn; Tyr75Pro; Tyr75Gln; Tyr75Arg; Tyr75Ser; Tyr75Thr; Tyr75Val; Tyr75Trp; Asn76Ala; Asn76Cys; Asn76Asp; Asn76Glu; Asn76Phe; Asn76Gly; Asn76His; Asn76Ile; Asn76Lys; Asn76Leu; Asn76Met; Asn76Pro; Asn76Gln; Asn76Arg; Asn76Ser; Asn76Thr; Asn76Val; Asn76Trp; Asn76Tyr; Pro77Ala; Pro77Cys; Pro77Asp; Pro77Glu; Pro77Phe; Pro77Gly; Pro77His; Pro77Ile; Pro77Lys; Pro77Leu; Pro77Met; Pro77Asn; Pro77Gln; Pro77Arg; Pro77Ser; Pro77Thr; Pro77Val; Pro77Trp; Pro77Tyr; Ile78Ala; Ile78Cys; Ile78Asp; Ile78Glu; Ile78Phe; Ile78Gly; Ile78His; Ile78Lys; Ile78Leu; Ile78Met; Ile78Asn; Ile78Pro; Ile78Gln; Ile78Arg; Ile78Ser; Ile78Thr; Ile78Val; Ile78Trp; Ile78Tyr; Thr79Ala; Thr79Cys; Thr79Asp; Thr79Glu; Thr79Phe; Thr79Gly; Thr79His; Thr79Ile; Thr79Lys; Thr79Leu; Thr79Met; Thr79Asn; Thr79Pro; Thr79Gln; Thr79Arg; Thr79Ser; Thr79Val; Thr79Trp; Thr79Tyr; Glu80Ala; Glu80Cys; Glu80Asp; Glu80Phe; Glu80Gly; Glu80His; Glu80Ile; Glu80Lys; Glu80Leu; Glu80Met; Glu80Asn; Glu80Pro; Glu80Gln; Glu80Arg; Glu80Ser; Glu80Thr; Glu80Val; Glu80Trp; Glu80Tyr; Lys81Ala; Lys81Cys; Lys81Asp; Lys81Glu; Lys81Phe; Lys81Gly; Lys81His; Lys81Ile; Lys81Leu; Lys81Met; Lys81Asn; Lys81Pro; Lys81Gln; Lys81Arg; Lys81Ser; Lys81Thr; Lys81Val; Lys81Trp; Lys81Tyr; His82Ala; His82Cys; His82Asp; His82Glu; His82Phe; His82Gly; His82Ile; His82Lys; His82Leu; His82Met; His82Asn; His82Pro; His82Gln; His8
2Arg; His82Ser; His82Thr; His82Val; His82Trp; His82Tyr; Val83Ala; Val83Cys; Val83Asp; Val83Glu; Val83Phe; Val83Gly; Val83His; Val83Ile; Val83Lys; Val83Leu; Val83Met; Val83Asn; Val83Pro; Val83Gln; Val83Arg; Val83Ser; Val83Thr; Val83Trp; Val83Tyr; Asp84Ala; Asp84Cys; Asp84Glu; Asp84Phe; Asp84Gly; Asp84His; Asp84Ile; Asp84Lys; Asp84Leu; Asp84Met; Asp84Asn; Asp84Pro; Asp84Gln; Asp84Arg; Asp84Ser; Asp84Thr; Asp84Val; Asp84Trp; Asp84Tyr; Thr85Ala; Thr85Cys; Thr85Asp; Thr85Glu; Thr85Phe; Thr85Gly; Thr85His; Thr85Ile; Thr85Lys; Thr85Leu; Thr85Met; Thr85Asn; Thr85Pro; Thr85Gln; Thr85Arg; Thr85Ser; Thr85Val; Thr85Trp; Thr85Tyr; Gly86Ala; Gly86Cys; Gly86Asp; Gly86Glu; Gly86Phe; Gly86His; Gly86Ile; Gly86Lys; Gly86Leu; Gly86Met; Gly86Asn; Gly86Pro; Gly86Gln; Gly86Arg; Gly86Ser; Gly86Thr; Gly86Val; Gly86Trp; Gly86Tyr; Met87Ala; Met87Cys; Met87Asp; Met87Glu; Met87Phe; Met87Gly; Met87His; Met87Ile; Met87Lys; Met87Leu; Met87Asn; Met87Pro; Met87Gln; Met87Arg; Met87Ser; Met87Thr; Met87Val; Met87Trp; Met87Tyr; Thr88Ala; Thr88Cys; Thr88Asp; Thr88Glu; Thr88Phe; Thr88Gly; Thr88His; Thr88Ile; Thr88Lys; Thr88Leu; Thr88Met; Thr88Asn; Thr88Pro; Thr88Gln; Thr88Arg; Thr88Ser; Thr88Val; Thr88Trp; Thr88Tyr; Leu89Ala; Leu89Cys; Leu89Asp; Leu89Glu; Leu89Phe; Leu89Gly; Leu89His; Leu89Ile; Leu89Lys; Leu89Met; Leu89Asn; Leu89Pro; Leu89Gln; Leu89Arg; Leu89Ser; Leu89Thr; Leu89Val; Leu89Trp; Leu89Tyr; Lys90Ala; Lys90Cys; Lys90Asp; Lys90Glu; Lys90Phe; Lys90Gly; Lys90His; Lys90Ile; Lys90Leu; Lys90Met; Lys90Asn; Lys90Pro; Lys90Gln; Lys90Arg; Lys90Ser; Lys90Thr; Lys90Val; Lys90Trp; Lys90Tyr; Glu91Ala; Glu91Cys; Glu91Asp; Glu91Phe; Glu91Gly; Glu91His; Glu91Ile; Glu91Lys; Glu91Leu; Glu91Met; Glu91Asn; Glu91Pro; Glu91Gln; Glu91Arg; Glu91Ser; Glu91Thr; Glu91Val; Glu91Trp; Glu91Tyr; Leu92Ala; Leu92Cys; Leu92Asp; Leu92Glu; Leu92Phe; Leu92Gly; Leu92His; Leu92Ile; Leu92Lys; Leu92Met; Leu92Asn; Leu92Pro; Leu92Gln; Leu92Arg; Leu92Ser; Leu92Thr; Leu92Val; Leu92Trp; Leu92Tyr; Ala93Cys; Ala93Asp; Ala93Glu; Ala93Phe; Ala93Gly; Ala93His; Ala93Ile; Ala93Lys; Ala93Leu; Ala93Met; Ala93Asn; Ala93Pro; Ala93Gln; Ala93Arg; Ala93Ser; Ala93Thr; Ala93Val; Ala93Trp; Ala93Tyr; Asp94Ala; Asp94Cys; Asp94Glu; Asp94Phe; Asp94Gly; Asp94His; Asp94Ile; Asp94Lys; Asp94Leu; Asp94Met; Asp94Asn; Asp94Pro; Asp94Gln; Asp94Arg; Asp94Ser; Asp94Thr; Asp94Val; Asp94Trp; Asp94Tyr; Ala95Cys; Ala95Asp; Ala95Glu; Ala95Phe; Ala95Gly; Ala95His; Ala95Ile; Ala95Lys; Ala95Leu; Ala95Met; Ala95Asn; Ala95Pro; Ala95Gln; Ala95Arg; Ala95Ser; Ala95Thr; Ala95Val; Ala95Trp; Ala95Tyr; Ser96Ala; Ser96Cys; Ser96Asp; Ser96Glu; Ser96Phe; Ser96Gly; Ser96His; Ser96Ile; Ser96Lys; Ser96Leu; Ser96Met; Ser96Asn; Ser96Pro; Ser96Gln; Ser96Arg; Ser96Thr; Ser96Val; Ser96Trp; Ser96Tyr; Leu97Ala; Leu97Cys; Leu97Asp; Leu97Glu; Leu97Phe; Leu97Gly; Leu97His; Leu97Ile; Leu97Lys; Leu97Met; Leu97Asn; Leu97Pro; Leu97Gln; Leu97Arg; Leu97Ser; Leu97Thr; Leu97Val; Leu97Trp; Leu97Tyr; Arg98Ala; Arg98Cys; Arg98Asp; Arg98Glu; Arg98Phe; Arg98Gly; Arg98His; Arg98Ile; Arg98Lys; Arg98Leu; Arg98Met; Arg98Asn; Arg98Pro; Arg98Gln; Arg98Ser; Arg98Thr; Arg98Val; Arg98Trp; Arg98Tyr; Tyr99Ala; Tyr99Cys; Tyr99Asp; Tyr99Glu; Tyr99Phe; Tyr99Gly; Tyr99His; Tyr99Ile; Tyr99Lys; Tyr99Leu; Tyr99Met; Tyr99Asn; Tyr99Pro; Tyr99Gln; Tyr99Arg; Tyr99Ser; Tyr99Thr; Tyr99Val; Tyr99Trp; Ser100Ala; Ser100Cys; Ser100Asp; Ser100Glu; Ser100Phe; Ser100Gly; Ser100His; Ser100Ile; Ser100Lys; Ser100Leu; Ser100Met; Ser100Asn; Ser100Pro; Ser100Gln; Ser100Arg; Ser100Thr; Ser100Val; Ser100Trp; Ser100Tyr; Asp101Ala; Asp101Cys; Asp101Glu; Asp101Phe; Asp101Gly; Asp101His; Asp101Ile; Asp101Lys; Asp101Leu; Asp101Met; Asp101Asn; Asp101Pro; Asp101Gln; Asp101Arg; Asp101Ser; Asp101Thr; Asp101Val; Asp101Trp; Asp101Tyr; Asn102Ala; Asn102Cys; Asn102Asp; Asn102Glu; Asn102Phe; Asn102Gly; Asn102His; Asn102Ile; Asn102Lys; Asn102Leu; Asn102Met; Asn102Pro; Asn102Gln; Asn102Arg; Asn102Ser; Asn102Thr; Asn102Val; Asn102Trp; Asn102Tyr; Ala103Cys; Ala103Asp; Ala103Glu; Ala103Phe; Ala103Gly; Ala103His; Ala103Ile; Ala103Lys; Ala103Leu; Ala103Met; Ala103Asn; Ala103Pro; Ala103Gln; Ala103Arg; Ala103Ser; Ala103Thr; Ala103Val; Ala103Trp; Ala103Tyr; Ala104Cys; Ala104Asp; Ala104Glu; Ala104Phe; Ala104Gly; Ala104His; Ala104Ile; Ala104Lys; Ala104Leu; Ala104Met; Ala104Asn; Ala104Pro; Ala104Gln; Ala104Arg; Ala104Ser; Ala104Thr; Ala104Val; Ala104Trp; Ala104Tyr; Gln105Ala; Gln105Cys; Gln105Asp; Gln105Glu; Gln105Phe; Gln105Gly; Gln105His; Gln105Ile; Gln105Lys; Gln105Leu; Gln105Met; Gln105Asn; Gln105Pro; Gln105Arg; Gln105Ser; Gln105Thr; Gln105Val; Gln105Trp; Gln105Tyr; Asn106Ala; Asn106Cys; Asn106Asp; Asn106Glu; Asn106Phe; Asn106Gly; Asn106His; Asn106Ile; Asn106Lys; Asn106Leu; Asn106Met; Asn106Pro; Asn106Gln; Asn106Arg; Asn106Ser; Asn106Thr; Asn106Val; Asn106Trp; Asn106Tyr; Leu107Ala; Leu107Cys; Leu107Asp; Leu107Glu; Leu107Phe; Leu107Gly; Leu107His; Leu107Ile; Leu107Lys; Leu107Met; Leu107Asn; Leu107Pro; Leu107Gln; Leu107Arg; Leu107Ser; Leu107Thr; Leu107Val; Leu107Trp; Leu107Tyr; Ile108Ala; Ile108Cys; Ile108Asp; Ile108Glu; Ile108Phe; Ile108Gly; Ile108His; Ile108Lys; Ile108Leu; Ile108Met; Ile108Asn; Ile108Pro; Ile108Gln; Ile108Arg; Ile108Ser
; Ile108Thr; Ile108Val; Ile108Trp; Ile108Tyr; Leu109Ala; Leu109Cys; Leu109Asp; Leu109Glu; Leu109Phe; Leu109Gly; Leu109His; Leu109Ile; Leu109Lys; Leu109Met; Leu109Asn; Leu109Pro; Leu109Gln; Leu109Arg; Leu109Ser; Leu109Thr; Leu109Val; Leu109Trp; Leu109Tyr; Lys110Ala; Lys110Cys; Lys110Asp; Lys110Glu; Lys110Phe; Lys110Gly; Lys110His; Lys110Ile; Lys110Leu; Lys110Met; Lys110Asn; Lys110Pro; Lys110Gln; Lys110Arg; Lys110Ser; Lys110Thr; Lys110Val; Lys110Trp; Lys110Tyr; Gln111Ala; Gln111Cys; Gln111Asp; Gln111Glu; Gln111Phe; Gln111Gly; Gln111His; Gln111Ile; Gln111Lys; Gln111Leu; Gln111Met; Gln111Asn; Gln111Pro; Gln111Arg; Gln111Ser; Gln111Thr; Gln111Val; Gln111Trp; Gln111Tyr; Ile112Ala; Ile112Cys; Ile112Asp; Ile112Glu; Ile112Phe; Ile112Gly; Ile112His; Ile112Lys; Ile112Leu; Ile112Met; Ile112Asn; Ile112Pro; Ile112Gln; Ile112Arg; Ile112Ser; Ile112Thr; Ile112Val; Ile112Trp; Ile112Tyr; Gly113Ala; Gly113Cys; Gly113Asp; Gly113Glu; Gly113Phe; Gly113His; Gly113Ile; Gly113Lys; Gly113Leu; Gly113Met; Gly113Asn; Gly113Pro; Gly113Gln; Gly113Arg; Gly113Ser; Gly113Thr; Gly113Val; Gly113Trp; Gly113Tyr; Gly114Ala; Gly114Cys; Gly114Asp; Gly114Glu; Gly114Phe; Gly114His; Gly114Ile; Gly114Lys; Gly114Leu; Gly114Met; Gly114Asn; Gly114Pro; Gly114Gln; Gly114Arg; Gly114Ser; Gly114Thr; Gly114Val; Gly114Trp; Gly114Tyr; Pro115Ala; Pro115Cys; Pro115Asp; Pro115Glu; Pro115Phe; Pro115Gly; Pro115His; Pro115Ile; Pro115Lys; Pro115Leu; Pro115Met; Pro115Asn; Pro115Gln; Pro115Arg; Pro115Ser; Pro115Thr; Pro115Val; Pro115Trp; Pro115Tyr; Glu116Ala; Glu116Cys; Glu116Asp; Glu116Phe; Glu116Gly; Glu116His; Glu116Ile; Glu116Lys; Glu116Leu; Glu116Met; Glu116Asn; Glu116Pro; Glu116Gln; Glu116Arg; Glu116Ser; Glu116Thr; Glu116Val; Glu116Trp; Glu116Tyr; Ser117Ala; Ser117Cys; Ser117Asp; Ser117Glu; Ser117Phe; Ser117Gly; Ser117His; Ser117Ile; Ser117Lys; Ser117Leu; Ser117Met; Ser117Asn; Ser117Pro; Ser117Gln; Ser117Arg; Ser117Thr; Ser117Val; Ser117Trp; Ser117Tyr; Leu118Ala; Leu118Cys; Leu118Asp; Leu118Glu; Leu118Phe; Leu118Gly; Leu118His; Leu118Ile; Leu118Lys; Leu118Met; Leu118Asn; Leu118Pro; Leu118Gln; Leu118Arg; Leu118Ser; Leu118Thr; Leu118Val; Leu118Trp; Leu118Tyr; Lys119Ala; Lys119Cys; Lys119Asp; Lys119Glu; Lys119Phe; Lys119Gly; Lys119His; Lys119Ile; Lys119Leu; Lys119Met; Lys119Asn; Lys119Pro; Lys119Gln; Lys119Arg; Lys119Ser; Lys119Thr; Lys119Val; Lys119Trp; Lys119Tyr; Lys120Ala; Lys120Cys; Lys120Asp; Lys120Glu; Lys120Phe; Lys120Gly; Lys120His; Lys120Ile; Lys120Leu; Lys120Met; Lys120Asn; Lys120Pro; Lys120Gln; Lys120Arg; Lys120Ser; Lys120Thr; Lys120Val; Lys120Trp; Lys120Tyr; Glu121Ala; Glu121Cys; Glu121Asp; Glu121Phe; Glu121Gly; Glu121His; Glu121Ile; Glu121Lys; Glu121Leu; Glu121Met; Glu121Asn; Glu121Pro; Glu121Gln; Glu121Arg; Glu121Ser; Glu121Thr; Glu121Val; Glu121Trp; Glu121Tyr; Leu122Ala; Leu122Cys; Leu122Asp; Leu122Glu; Leu122Phe; Leu122Gly; Leu122His; Leu122Ile; Leu122Lys; Leu122Met; Leu122Asn; Leu122Pro; Leu122Gln; Leu122Arg; Leu122Ser; Leu122Thr; Leu122Val; Leu122Trp; Leu122Tyr; Arg123Ala; Arg123Cys; Arg123Asp; Arg123Glu; Arg123Phe; Arg123Gly; Arg123His; Arg123Ile; Arg123Lys; Arg123Leu; Arg123Met; Arg123Asn; Arg123Pro; Arg123Gln; Arg123Ser; Arg123Thr; Arg123Val; Arg123Trp; Arg123Tyr; Lys124Ala; Lys124Cys; Lys124Asp; Lys124Glu; Lys124Phe; Lys124Gly; Lys124His; Lys124Ile; Lys124Leu; Lys124Met; Lys124Asn; Lys124Pro; Lys124Gln; Lys124Arg; Lys124Ser; Lys124Thr; Lys124Val; Lys124Trp; Lys124Tyr; Ile125Ala; Ile125Cys; Ile125Asp; Ile125Glu; Ile125Phe; Ile125Gly; Ile125His; Ile125Lys; Ile125Leu; Ile125Met; Ile125Asn; Ile125Pro; Ile125Gln; Ile125Arg; Ile125Ser; Ile125Thr; Ile125Val; Ile125Trp; Ile125Tyr; Gly126Ala; Gly126Cys; Gly126Asp; Gly126Glu; Gly126Phe; Gly126His; Gly126Ile; Gly126Lys; Gly126Leu; Gly126Met; Gly126Asn; Gly126Pro; Gly126Gln; Gly126Arg; Gly126Ser; Gly126Thr; Gly126Val; Gly126Trp; Gly126Tyr; Asp127Ala; Asp127Cys; Asp127Glu; Asp127Phe; Asp127Gly; Asp127His; Asp127Ile; Asp127Lys; Asp127Leu; Asp127Met; Asp127Asn; Asp127Pro; Asp127Gln; Asp127Arg; Asp127Ser; Asp127Thr; Asp127Val; Asp127Trp; Asp127Tyr; Glu128Ala; Glu128Cys; Glu128Asp; Glu128Phe; Glu128Gly; Glu128His; Glu128Ile; Glu128Lys; Glu128Leu; Glu128Met; Glu128Asn; Glu128Pro; Glu128Gln; Glu128Arg; Glu128Ser; Glu128Thr; Glu128Val; Glu128Trp; Glu128Tyr; Val129Ala; Val129Cys; Val129Asp; Val129Glu; Val129Phe; Val129Gly; Val129His; Val129Ile; Val129Lys; Val129Leu; Val129Met; Val129Asn; Val129Pro; Val129Gln; Val129Arg; Val129Ser; Val129Thr; Val129Trp; Val129Tyr; Thr130Ala; Thr130Cys; Thr130Asp; Thr130Glu; Thr130Phe; Thr130Gly; Thr130His; Thr130Ile; Thr130Lys; Thr130Leu; Thr130Met; Thr130Asn; Thr130Pro; Thr130Gln; Thr130Arg; Thr130Ser; Thr130Val; Thr130Trp; Thr130Tyr; Asn131Ala; Asn131Cys; Asn131Asp; Asn131Glu; Asn131Phe; Asn131Gly; Asn131His; Asn131Ile; Asn131Lys; Asn131Leu; Asn131Met; Asn131Pro; Asn131Gln; Asn131Arg; Asn131Ser; Asn131Thr; Asn131Val; Asn131Trp; Asn131Tyr; Pro132Ala; Pro132Cys; Pro132Asp; Pro132Glu; Pro132Phe; Pro132Gly; Pro132His; Pro132Ile; Pro132Lys; Pro132Leu; Pro132Met; Pro132Asn; Pro132Gln; Pro132Arg; Pro132Ser; Pro132Thr; Pro132Val; Pro132Trp; Pro132Tyr; Glu133Ala; Glu133Cys; Glu133Asp; Glu133Phe; Glu133Gly; Glu1
33His; Glu133Ile; Glu133Lys; Glu133Leu; Glu133Met; Glu133Asn; Glu133Pro; Glu133Gln; Glu133Arg; Glu133Ser; Glu133Thr; Glu133Val; Glu133Trp; Glu133Tyr; Arg134Ala; Arg134Cys; Arg134Asp; Arg134Glu; Arg134Phe; Arg134Gly; Arg134His; Arg134Ile; Arg134Lys; Arg134Leu; Arg134Met; Arg134Asn; Arg134Pro; Arg134Gln; Arg134Ser; Arg134Thr; Arg134Val; Arg134Trp; Arg134Tyr; Phe135Ala; Phe135Cys; Phe135Asp; Phe135Glu; Phe135Gly; Phe135His; Phe135Ile; Phe135Lys; Phe135Leu; Phe135Met; Phe135Asn; Phe135Pro; Phe135Gln; Phe135Arg; Phe135Ser; Phe135Thr; Phe135Val; Phe135Trp; Phe135Tyr; Glu136Ala; Glu136Cys; Glu136Asp; Glu136Phe; Glu136Gly; Glu136His; Glu136Ile; Glu136Lys; Glu136Leu; Glu136Met; Glu136Asn; Glu136Pro; Glu136Gln; Glu136Arg; Glu136Ser; Glu136Thr; Glu136Val; Glu136Trp; Glu136Tyr; Pro137Ala; Pro137Cys; Pro137Asp; Pro137Glu; Pro137Phe; Pro137Gly; Pro137His; Pro137Ile; Pro137Lys; Pro137Leu; Pro137Met; Pro137Asn; Pro137Gln; Pro137Arg; Pro137Ser; Pro137Thr; Pro137Val; Pro137Trp; Pro137Tyr; Glu138Ala; Glu138Cys; Glu138Asp; Glu138Phe; Glu138Gly; Glu138His; Glu138Ile; Glu138Lys; Glu138Leu; Glu138Met; Glu138Asn; Glu138Pro; Glu138Gln; Glu138Arg; Glu138Ser; Glu138Thr; Glu138Val; Glu138Trp; Glu138Tyr; Leu139Ala; Leu139Cys; Leu139Asp; Leu139Glu; Leu139Phe; Leu139Gly; Leu139His; Leu139Ile; Leu139Lys; Leu139Met; Leu139Asn; Leu139Pro; Leu139Gln; Leu139Arg; Leu139Ser; Leu139Thr; Leu139Val; Leu139Trp; Leu139Tyr; Asn140Ala; Asn140Cys; Asn140Asp; Asn140Glu; Asn140Phe; Asn140Gly; Asn140His; Asn140Ile; Asn140Lys; Asn140Leu; Asn140Met; Asn140Pro; Asn140Gln; Asn140Arg; Asn140Ser; Asn140Thr; Asn140Val; Asn140Trp; Asn140Tyr; Glu141Ala; Glu141Cys; Glu141Asp; Glu141Phe; Glu141Gly; Glu141His; Glu141Ile; Glu141Lys; Glu141Leu; Glu141Met; Glu141Asn; Glu141Pro; Glu141Gln; Glu141Arg; Glu141Ser; Glu141Thr; Glu141Val; Glu141Trp; Glu141Tyr; Val142Ala; Val142Cys; Val142Asp; Val142Glu; Val142Phe; Val142Gly; Val142His; Val142Ile; Val142Lys; Val142Leu; Val142Met; Val142Asn; Val142Pro; Val142Gln; Val142Arg; Val142Ser; Val142Thr; Val142Trp; Val142Tyr; Asn143Ala; Asn143Cys; Asn143Asp; Asn143Glu; Asn143Phe; Asn143Gly; Asn143His; Asn143Ile; Asn143Lys; Asn143Leu; Asn143Met; Asn143Pro; Asn143Gln; Asn143Arg; Asn143Ser; Asn143Thr; Asn143Val; Asn143Trp; Asn143Tyr; Pro144Ala; Pro144Cys; Pro144Asp; Pro144Glu; Pro144Phe; Pro144Gly; Pro144His; Pro144Ile; Pro144Lys; Pro144Leu; Pro144Met; Pro144Asn; Pro144Gln; Pro144Arg; Pro144Ser; Pro144Thr; Pro144Val; Pro144Trp; Pro144Tyr; Gly145Ala; Gly145Cys; Gly145Asp; Gly145Glu; Gly145Phe; Gly145His; Gly145Ile; Gly145Lys; Gly145Leu; Gly145Met; Gly145Asn; Gly145Pro; Gly145Gln; Gly145Arg; Gly145Ser; Gly145Thr; Gly145Val; Gly145Trp; Gly145Tyr; Glu146Ala; Glu146Cys; Glu146Asp; Glu146Phe; Glu146Gly; Glu146His; Glu146Ile; Glu146Lys; Glu146Leu; Glu146Met; Glu146Asn; Glu146Pro; Glu146Gln; Glu146Arg; Glu146Ser; Glu146Thr; Glu146Val; Glu146Trp; Glu146Tyr; Thr147Ala; Thr147Cys; Thr147Asp; Thr147Glu; Thr147Phe; Thr147Gly; Thr147His; Thr147Ile; Thr147Lys; Thr147Leu; Thr147Met; Thr147Asn; Thr147Pro; Thr147Gln; Thr147Arg; Thr147Ser; Thr147Val; Thr147Trp; Thr147Tyr; Gln148Ala; Gln148Cys; Gln148Asp; Gln148Glu; Gln148Phe; Gln148Gly; Gln148His; Gln148Ile; Gln148Lys; Gln148Leu; Gln148Met; Gln148Asn; Gln148Pro; Gln148Arg; Gln148Ser; Gln148Thr; Gln148Val; Gln148Trp; Gln148Tyr; Asp149Ala; Asp149Cys; Asp149Glu; Asp149Phe; Asp149Gly; Asp149His; Asp149Ile; Asp149Lys; Asp149Leu; Asp149Met; Asp149Asn; Asp149Pro; Asp149Gln; Asp149Arg; Asp149Ser; Asp149Thr; Asp149Val; Asp149Trp; Asp149Tyr; Thr150Ala; Thr150Cys; Thr150Asp; Thr150Glu; Thr150Phe; Thr150Gly; Thr150His; Thr150Ile; Thr150Lys; Thr150Leu; Thr150Met; Thr150Asn; Thr150Pro; Thr150Gln; Thr150Arg; Thr150Ser; Thr150Val; Thr150Trp; Thr150Tyr; Ser151Ala; Ser151Cys; Ser151Asp; Ser151Glu; Ser151Phe; Ser151Gly; Ser151His; Ser151Ile; Ser151Lys; Ser151Leu; Ser151Met; Ser151Asn; Ser151Pro; Ser151Gln; Ser151Arg; Ser151Thr; Ser151Val; Ser151Trp; Ser151Tyr; Thr152Ala; Thr152Cys; Thr152Asp; Thr152Glu; Thr152Phe; Thr152Gly; Thr152His; Thr152Ile; Thr152Lys; Thr152Leu; Thr152Met; Thr152Asn; Thr152Pro; Thr152Gln; Thr152Arg; Thr152Ser; Thr152Val; Thr152Trp; Thr152Tyr; Ala153Cys; Ala153Asp; Ala153Glu; Ala153Phe; Ala153Gly; Ala153His; Ala153Ile; Ala153Lys; Ala153Leu; Ala153Met; Ala153Asn; Ala153Pro; Ala153Gln; Ala153Arg; Ala153Ser; Ala153Thr; Ala153Val; Ala153Trp; Ala153Tyr; Arg154Ala; Arg154Cys; Arg154Asp; Arg154Glu; Arg154Phe; Arg154Gly; Arg154His; Arg154Ile; Arg154Lys; Arg154Leu; Arg154Met; Arg154Asn; Arg154Pro; Arg154Gln; Arg154Ser; Arg154Thr; Arg154Val; Arg154Trp; Arg154Tyr; Ala155Cys; Ala155Asp; Ala155Glu; Ala155Phe; Ala155Gly; Ala155His; Ala155Ile; Ala155Lys; Ala155Leu; Ala155Met; Ala155Asn; Ala155Pro; Ala155Gln; Ala155Arg; Ala155Ser; Ala155Thr; Ala155Val; Ala155Trp; Ala155Tyr; Leu156Ala; Leu156Cys; Leu156Asp; Leu156Glu; Leu156Phe; Leu156Gly; Leu156His; Leu156Ile; Leu156Lys; Leu156Met; Leu156Asn; Leu156Pro; Leu156Gln; Leu156Arg; Leu156Ser; Leu156Thr; Leu156Val; Leu156Trp; Leu156Tyr; Val157Ala; Val157Cys; Val157Asp; Val157Glu; Val157Phe; Val157Gly; Val157His; Val157Ile; Val157Lys; Val157Leu; Val157Met; Val157Asn; Val157Pro; Val157Gln; Val157Arg;
Val157Ser; Val157Thr; Val157Trp; Val157Tyr; Thr158Ala; Thr158Cys; Thr158Asp; Thr158Glu; Thr158Phe; Thr158Gly; Thr158His; Thr158Ile; Thr158Lys; Thr158Leu; Thr158Met; Thr158Asn; Thr158Pro; Thr158Gln; Thr158Arg; Thr158Ser; Thr158Val; Thr158Trp; Thr158Tyr; Ser159Ala; Ser159Cys; Ser159Asp; Ser159Glu; Ser159Phe; Ser159Gly; Ser159His; Ser159Ile; Ser159Lys; Ser159Leu; Ser159Met; Ser159Asn; Ser159Pro; Ser159Gln; Ser159Arg; Ser159Thr; Ser159Val; Ser159Trp; Ser159Tyr; Leu160Ala; Leu160Cys; Leu160Asp; Leu160Glu; Leu160Phe; Leu160Gly; Leu160His; Leu160Ile; Leu160Lys; Leu160Met; Leu160Asn; Leu160Pro; Leu160Gln; Leu160Arg; Leu160Ser; Leu160Thr; Leu160Val; Leu160Trp; Leu160Tyr; Arg161Ala; Arg161Cys; Arg161Asp; Arg161Glu; Arg161Phe; Arg161Gly; Arg161His; Arg161Ile; Arg161Lys; Arg161Leu; Arg161Met; Arg161Asn; Arg161Pro; Arg161Gln; Arg161Ser; Arg161Thr; Arg161Val; Arg161Trp; Arg161Tyr; Ala162Cys; Ala162Asp; Ala162Glu; Ala162Phe; Ala162Gly; Ala162His; Ala162Ile; Ala162Lys; Ala162Leu; Ala162Met; Ala162Asn; Ala162Pro; Ala162Gln; Ala162Arg; Ala162Ser; Ala162Thr; Ala162Val; Ala162Trp; Ala162Tyr; Phe163Ala; Phe163Cys; Phe163Asp; Phe163Glu; Phe163Gly; Phe163His; Phe163Ile; Phe163Lys; Phe163Leu; Phe163Met; Phe163Asn; Phe163Pro; Phe163Gln; Phe163Arg; Phe163Ser; Phe163Thr; Phe163Val; Phe163Trp; Phe163Tyr; Ala164Cys; Ala164Asp; Ala164Glu; Ala164Phe; Ala164Gly; Ala164His; Ala164Ile; Ala164Lys; Ala164Leu; Ala164Met; Ala164Asn; Ala164Pro; Ala164Gln; Ala164Arg; Ala164Ser; Ala164Thr; Ala164Val; Ala164Trp; Ala164Tyr; Leu165Ala; Leu165Cys; Leu165Asp; Leu165Glu; Leu165Phe; Leu165Gly; Leu165His; Leu165Ile; Leu165Lys; Leu165Met; Leu165Asn; Leu165Pro; Leu165Gln; Leu165Arg; Leu165Ser; Leu165Thr; Leu165Val; Leu165Trp; Leu165Tyr; Glu166Ala; Glu166Cys; Glu166Asp; Glu166Phe; Glu166Gly; Glu166His; Glu166Ile; Glu166Lys; Glu166Leu; Glu166Met; Glu166Asn; Glu166Pro; Glu166Gln; Glu166Arg; Glu166Ser; Glu166Thr; Glu166Val; Glu166Trp; Glu166Tyr; Asp167Ala; Asp167Cys; Asp167Glu; Asp167Phe; Asp167Gly; Asp167His; Asp167Ile; Asp167Lys; Asp167Leu; Asp167Met; Asp167Asn; Asp167Pro; Asp167Gln; Asp167Arg; Asp167Ser; Asp167Thr; Asp167Val; Asp167Trp; Asp167Tyr; Lys168Ala; Lys168Cys; Lys168Asp; Lys168Glu; Lys168Phe; Lys168Gly; Lys168His; Lys168Ile; Lys168Leu; Lys168Met; Lys168Asn; Lys168Pro; Lys168Gln; Lys168Arg; Lys168Ser; Lys168Thr; Lys168Val; Lys168Trp; Lys168Tyr; Leu169Ala; Leu169Cys; Leu169Asp; Leu169Glu; Leu169Phe; Leu169Gly; Leu169His; Leu169Ile; Leu169Lys; Leu169Met; Leu169Asn; Leu169Pro; Leu169Gln; Leu169Arg; Leu169Ser; Leu169Thr; Leu169Val; Leu169Trp; Leu169Tyr; Pro170Ala; Pro170Cys; Pro170Asp; Pro170Glu; Pro170Phe; Pro170Gly; Pro170His; Pro170Ile; Pro170Lys; Pro170Leu; Pro170Met; Pro170Asn; Pro170Gln; Pro170Arg; Pro170Ser; Pro170Thr; Pro170Val; Pro170Trp; Pro170Tyr; Ser171Ala; Ser171Cys; Ser171Asp; Ser171Glu; Ser171Phe; Ser171Gly; Ser171His; Ser171Ile; Ser171Lys; Ser171Leu; Ser171Met; Ser171Asn; Ser171Pro; Ser171Gln; Ser171Arg; Ser171Thr; Ser171Val; Ser171Trp; Ser171Tyr; Glu172Ala; Glu172Cys; Glu172Asp; Glu172Phe; Glu172Gly; Glu172His; Glu172Ile; Glu172Lys; Glu172Leu; Glu172Met; Glu172Asn; Glu172Pro; Glu172Gln; Glu172Arg; Glu172Ser; Glu172Thr; Glu172Val; Glu172Trp; Glu172Tyr; Lys173Ala; Lys173Cys; Lys173Asp; Lys173Glu; Lys173Phe; Lys173Gly; Lys173His; Lys173Ile; Lys173Leu; Lys173Met; Lys173Asn; Lys173Pro; Lys173Gln; Lys173Arg; Lys173Ser; Lys173Thr; Lys173Val; Lys173Trp; Lys173Tyr; Arg174Ala; Arg174Cys; Arg174Asp; Arg174Glu; Arg174Phe; Arg174Gly; Arg174His; Arg174Ile; Arg174Lys; Arg174Leu; Arg174Met; Arg174Asn; Arg174Pro; Arg174Gln; Arg174Ser; Arg174Thr; Arg174Val; Arg174Trp; Arg174Tyr; Glu175Ala; Glu175Cys; Glu175Asp; Glu175Phe; Glu175Gly; Glu175His; Glu175Ile; Glu175Lys; Glu175Leu; Glu175Met; Glu175Asn; Glu175Pro; Glu175Gln; Glu175Arg; Glu175Ser; Glu175Thr; Glu175Val; Glu175Trp; Glu175Tyr; Leu176Ala; Leu176Cys; Leu176Asp; Leu176Glu; Leu176Phe; Leu176Gly; Leu176His; Leu176Ile; Leu176Lys; Leu176Met; Leu176Asn; Leu176Pro; Leu176Gln; Leu176Arg; Leu176Ser; Leu176Thr; Leu176Val; Leu176Trp; Leu176Tyr; Leu177Ala; Leu177Cys; Leu177Asp; Leu177Glu; Leu177Phe; Leu177Gly; Leu177His; Leu177Ile; Leu177Lys; Leu177Met; Leu177Asn; Leu177Pro; Leu177Gln; Leu177Arg; Leu177Ser; Leu177Thr; Leu177Val; Leu177Trp; Leu177Tyr; Ile178Ala; Ile178Cys; Ile178Asp; Ile178Glu; Ile178Phe; Ile178Gly; Ile178His; Ile178Lys; Ile178Leu; Ile178Met; Ile178Asn; Ile178Pro; Ile178Gln; Ile178Arg; Ile178Ser; Ile178Thr; Ile178Val; Ile178Trp; Ile178Tyr; Asp179Ala; Asp179Cys; Asp179Glu; Asp179Phe; Asp179Gly; Asp179His; Asp179Ile; Asp179Lys; Asp179Leu; Asp179Met; Asp179Asn; Asp179Pro; Asp179Gln; Asp179Arg; Asp179Ser; Asp179Thr; Asp179Val; Asp179Trp; Asp179Tyr; Trp180Ala; Trp180Cys; Trp180Asp; Trp180Glu; Trp180Phe; Trp180Gly; Trp180His; Trp180Ile; Trp180Lys; Trp180Leu; Trp180Met; Trp180Asn; Trp180Pro; Trp180Gln; Trp180Arg; Trp180Ser; Trp180Thr; Trp180Val; Trp180Tyr; Met181Ala; Met181Cys; Met181Asp; Met181Glu; Met181Phe; Met181Gly; Met181His; Met181Ile; Met181Lys; Met181Leu; Met181Asn; Met181Pro; Met181Gln; Met181Arg; Met181Ser; Met181Thr; Met181Val; Met181Trp; Met181Tyr; Lys182Ala; Lys182Cys; Lys182Asp; Lys182Glu; Lys182Phe; Lys18
2Gly; Lys182His; Lys182Ile; Lys182Leu; Lys182Met; Lys182Asn; Lys182Pro; Lys182Gln; Lys182Arg; Lys182Ser; Lys182Thr; Lys182Val; Lys182Trp; Lys182Tyr; Arg183Ala; Arg183Cys; Arg183Asp; Arg183Glu; Arg183Phe; Arg183Gly; Arg183His; Arg183Ile; Arg183Lys; Arg183Leu; Arg183Met; Arg183Asn; Arg183Pro; Arg183Gln; Arg183Ser; Arg183Thr; Arg183Val; Arg183Trp; Arg183Tyr; Asn184Ala; Asn184Cys; Asn184Asp; Asn184Glu; Asn184Phe; Asn184Gly; Asn184His; Asn184Ile; Asn184Lys; Asn184Leu; Asn184Met; Asn184Pro; Asn184Gln; Asn184Arg; Asn184Ser; Asn184Thr; Asn184Val; Asn184Trp; Asn184Tyr; Thr185Ala; Thr185Cys; Thr185Asp; Thr185Glu; Thr185Phe; Thr185Gly; Thr185His; Thr185Ile; Thr185Lys; Thr185Leu; Thr185Met; Thr185Asn; Thr185Pro; Thr185Gln; Thr185Arg; Thr185Ser; Thr185Val; Thr185Trp; Thr185Tyr; Thr186Ala; Thr186Cys; Thr186Asp; Thr186Glu; Thr186Phe; Thr186Gly; Thr186His; Thr186Ile; Thr186Lys; Thr186Leu; Thr186Met; Thr186Asn; Thr186Pro; Thr186Gln; Thr186Arg; Thr186Ser; Thr186Val; Thr186Trp; Thr186Tyr; Gly187Ala; Gly187Cys; Gly187Asp; Gly187Glu; Gly187Phe; Gly187His; Gly187Ile; Gly187Lys; Gly187Leu; Gly187Met; Gly187Asn; Gly187Pro; Gly187Gln; Gly187Arg; Gly187Ser; Gly187Thr; Gly187Val; Gly187Trp; Gly187Tyr; Asp188Ala; Asp188Cys; Asp188Glu; Asp188Phe; Asp188Gly; Asp188His; Asp188Ile; Asp188Lys; Asp188Leu; Asp188Met; Asp188Asn; Asp188Pro; Asp188Gln; Asp188Arg; Asp188Ser; Asp188Thr; Asp188Val; Asp188Trp; Asp188Tyr; Ala189Cys; Ala189Asp; Ala189Glu; Ala189Phe; Ala189Gly; Ala189His; Ala189Ile; Ala189Lys; Ala189Leu; Ala189Met; Ala189Asn; Ala189Pro; Ala189Gln; Ala189Arg; Ala189Ser; Ala189Thr; Ala189Val; Ala189Trp; Ala189Tyr; Leu190Ala; Leu190Cys; Leu190Asp; Leu190Glu; Leu190Phe; Leu190Gly; Leu190His; Leu190Ile; Leu190Lys; Leu190Met; Leu190Asn; Leu190Pro; Leu190Gln; Leu190Arg; Leu190Ser; Leu190Thr; Leu190Val; Leu190Trp; Leu190Tyr; Ile191Ala; Ile191Cys; Ile191Asp; Ile191Glu; Ile191Phe; Ile191Gly; Ile191His; Ile191Lys; Ile191Leu; Ile191Met; Ile191Asn; Ile191Pro; Ile191Gln; Ile191Arg; Ile191Ser; Ile191Thr; Ile191Val; Ile191Trp; Ile191Tyr; Arg192Ala; Arg192Cys; Arg192Asp; Arg192Glu; Arg192Phe; Arg192Gly; Arg192His; Arg192Ile; Arg192Lys; Arg192Leu; Arg192Met; Arg192Asn; Arg192Pro; Arg192Gln; Arg192Ser; Arg192Thr; Arg192Val; Arg192Trp; Arg192Tyr; Ala193Cys; Ala193Asp; Ala193Glu; Ala193Phe; Ala193Gly; Ala193His; Ala193Ile; Ala193Lys; Ala193Leu; Ala193Met; Ala193Asn; Ala193Pro; Ala193Gln; Ala193Arg; Ala193Ser; Ala193Thr; Ala193Val; Ala193Trp; Ala193Tyr; Gly194Ala; Gly194Cys; Gly194Asp; Gly194Glu; Gly194Phe; Gly194His; Gly194Ile; Gly194Lys; Gly194Leu; Gly194Met; Gly194Asn; Gly194Pro; Gly194Gln; Gly194Arg; Gly194Ser; Gly194Thr; Gly194Val; Gly194Trp; Gly194Tyr; Val195Ala; Val195Cys; Val195Asp; Val195Glu; Val195Phe; Val195Gly; Val195His; Val195Ile; Val195Lys; Val195Leu; Val195Met; Val195Asn; Val195Pro; Val195Gln; Val195Arg; Val195Ser; Val195Thr; Val195Trp; Val195Tyr; Pro196Ala; Pro196Cys; Pro196Asp; Pro196Glu; Pro196Phe; Pro196Gly; Pro196His; Pro196Ile; Pro196Lys; Pro196Leu; Pro196Met; Pro196Asn; Pro196Gln; Pro196Arg; Pro196Ser; Pro196Thr; Pro196Val; Pro196Trp; Pro196Tyr; Asp197Ala; Asp197Cys; Asp197Glu; Asp197Phe; Asp197Gly; Asp197His; Asp197Ile; Asp197Lys; Asp197Leu; Asp197Met; Asp197Asn; Asp197Pro; Asp197Gln; Asp197Arg; Asp197Ser; Asp197Thr; Asp197Val; Asp197Trp; Asp197Tyr; Gly198Ala; Gly198Cys; Gly198Asp; Gly198Glu; Gly198Phe; Gly198His; Gly198Ile; Gly198Lys; Gly198Leu; Gly198Met; Gly198Asn; Gly198Pro; Gly198Gln; Gly198Arg; Gly198Ser; Gly198Thr; Gly198Val; Gly198Trp; Gly198Tyr; Trp199Ala; Trp199Cys; Trp199Asp; Trp199Glu; Trp199Phe; Trp199Gly; Trp199His; Trp199Ile; Trp199Lys; Trp199Leu; Trp199Met; Trp199Asn; Trp199Pro; Trp199Gln; Trp199Arg; Trp199Ser; Trp199Thr; Trp199Val; Trp199Tyr; Glu200Ala; Glu200Cys; Glu200Asp; Glu200Phe; Glu200Gly; Glu200His; Glu200Ile; Glu200Lys; Glu200Leu; Glu200Met; Glu200Asn; Glu200Pro; Glu200Gln; Glu200Arg; Glu200Ser; Glu200Thr; Glu200Val; Glu200Trp; Glu200Tyr; Val201Ala; Val201Cys; Val201Asp; Val201Glu; Val201Phe; Val201Gly; Val201His; Val201Ile; Val201Lys; Val201Leu; Val201Met; Val201Asn; Val201Pro; Val201Gln; Val201Arg; Val201Ser; Val201Thr; Val201Trp; Val201Tyr; Ala202Cys; Ala202Asp; Ala202Glu; Ala202Phe; Ala202Gly; Ala202His; Ala202Ile; Ala202Lys; Ala202Leu; Ala202Met; Ala202Asn; Ala202Pro; Ala202Gln; Ala202Arg; Ala202Ser; Ala202Thr; Ala202Val; Ala202Trp; Ala202Tyr; Asp203Ala; Asp203Cys; Asp203Glu; Asp203Phe; Asp203Gly; Asp203His; Asp203Ile; Asp203Lys; Asp203Leu; Asp203Met; Asp203Asn; Asp203Pro; Asp203Gln; Asp203Arg; Asp203Ser; Asp203Thr; Asp203Val; Asp203Trp; Asp203Tyr; Lys204Ala; Lys204Cys; Lys204Asp; Lys204Glu; Lys204Phe; Lys204Gly; Lys204His; Lys204Ile; Lys204Leu; Lys204Met; Lys204Asn; Lys204Pro; Lys204Gln; Lys204Arg; Lys204Ser; Lys204Thr; Lys204Val; Lys204Trp; Lys204Tyr; Thr205Ala; Thr205Cys; Thr205Asp; Thr205Glu; Thr205Phe; Thr205Gly; Thr205His; Thr205Ile; Thr205Lys; Thr205Leu; Thr205Met; Thr205Asn; Thr205Pro; Thr205Gln; Thr205Arg; Thr205Ser; Thr205Val; Thr205Trp; Thr205Tyr; Gly206Ala; Gly206Cys; Gly206Asp; Gly206Glu; Gly206Phe; Gly206His; Gly206Ile; Gly206Lys; Gly206Leu; Gly206Met; Gly206Asn; Gly206Pro; Gly206Gln; Gly206Arg; Gly206Ser;
Gly206Thr; Gly206Val; Gly206Trp; Gly206Tyr; Ala207Cys; Ala207Asp; Ala207Glu; Ala207Phe; Ala207Gly; Ala207His; Ala207Ile; Ala207Lys; Ala207Leu; Ala207Met; Ala207Asn; Ala207Pro; Ala207Gln; Ala207Arg; Ala207Ser; Ala207Thr; Ala207Val; Ala207Trp; Ala207Tyr; Ala208Cys; Ala208Asp; Ala208Glu; Ala208Phe; Ala208Gly; Ala208His; Ala208Ile; Ala208Lys; Ala208Leu; Ala208Met; Ala208Asn; Ala208Pro; Ala208Gln; Ala208Arg; Ala208Ser; Ala208Thr; Ala208Val; Ala208Trp; Ala208Tyr; Ser209Ala; Ser209Cys; Ser209Asp; Ser209Glu; Ser209Phe; Ser209Gly; Ser209His; Ser209Ile; Ser209Lys; Ser209Leu; Ser209Met; Ser209Asn; Ser209Pro; Ser209Gln; Ser209Arg; Ser209Thr; Ser209Val; Ser209Trp; Ser209Tyr; Tyr210Ala; Tyr210Cys; Tyr210Asp; Tyr210Glu; Tyr210Phe; Tyr210Gly; Tyr210His; Tyr210Ile; Tyr210Lys; Tyr210Leu; Tyr210Met; Tyr210Asn; Tyr210Pro; Tyr210Gln; Tyr210Arg; Tyr210Ser; Tyr210Thr; Tyr210Val; Tyr210Trp; Gly211Ala; Gly211Cys; Gly211Asp; Gly211Glu; Gly211Phe; Gly211His; Gly211Ile; Gly211Lys; Gly211Leu; Gly211Met; Gly211Asn; Gly211Pro; Gly211Gln; Gly211Arg; Gly211Ser; Gly211Thr; Gly211Val; Gly211Trp; Gly211Tyr; Thr212Ala; Thr212Cys; Thr212Asp; Thr212Glu; Thr212Phe; Thr212Gly; Thr212His; Thr212Ile; Thr212Lys; Thr212Leu; Thr212Met; Thr212Asn; Thr212Pro; Thr212Gln; Thr212Arg; Thr212Ser; Thr212Val; Thr212Trp; Thr212Tyr; Arg213Ala; Arg213Cys; Arg213Asp; Arg213Glu; Arg213Phe; Arg213Gly; Arg213His; Arg213Ile; Arg213Lys; Arg213Leu; Arg213Met; Arg213Asn; Arg213Pro; Arg213Gln; Arg213Ser; Arg213Thr; Arg213Val; Arg213Trp; Arg213Tyr; Asn214Ala; Asn214Cys; Asn214Asp; Asn214Glu; Asn214Phe; Asn214Gly; Asn214His; Asn214Ile; Asn214Lys; Asn214Leu; Asn214Met; Asn214Pro; Asn214Gln; Asn214Arg; Asn214Ser; Asn214Thr; Asn214Val; Asn214Trp; Asn214Tyr; Asp215Ala; Asp215Cys; Asp215Glu; Asp215Phe; Asp215Gly; Asp215His; Asp215Ile; Asp215Lys; Asp215Leu; Asp215Met; Asp215Asn; Asp215Pro; Asp215Gln; Asp215Arg; Asp215Ser; Asp215Thr; Asp215Val; Asp215Trp; Asp215Tyr; Ile216Ala; Ile216Cys; Ile216Asp; Ile216Glu; Ile216Phe; Ile216Gly; Ile216His; Ile216Lys; Ile216Leu; Ile216Met; Ile216Asn; Ile216Pro; Ile216Gln; Ile216Arg; Ile216Ser; Ile216Thr; Ile216Val; Ile216Trp; Ile216Tyr; Ala217Cys; Ala217Asp; Ala217Glu; Ala217Phe; Ala217Gly; Ala217His; Ala217Ile; Ala217Lys; Ala217Leu; Ala217Met; Ala217Asn; Ala217Pro; Ala217Gln; Ala217Arg; Ala217Ser; Ala217Thr; Ala217Val; Ala217Trp; Ala217Tyr; Ile218Ala; Ile218Cys; Ile218Asp; Ile218Glu; Ile218Phe; Ile218Gly; Ile218His; Ile218Lys; Ile218Leu; Ile218Met; Ile218Asn; Ile218Pro; Ile218Gln; Ile218Arg; Ile218Ser; Ile218Thr; Ile218Val; Ile218Trp; Ile218Tyr; Ile219Ala; Ile219Cys; Ile219Asp; Ile219Glu; Ile219Phe; Ile219Gly; Ile219His; Ile219Lys; Ile219Leu; Ile219Met; Ile219Asn; Ile219Pro; Ile219Gln; Ile219Arg; Ile219Ser; Ile219Thr; Ile219Val; Ile219Trp; Ile219Tyr; Trp220Ala; Trp220Cys; Trp220Asp; Trp220Glu; Trp220Phe; Trp220Gly; Trp220His; Trp220Ile; Trp220Lys; Trp220Leu; Trp220Met; Trp220Asn; Trp220Pro; Trp220Gln; Trp220Arg; Trp220Ser; Trp220Thr; Trp220Val; Trp220Tyr; Pro221Ala; Pro221Cys; Pro221Asp; Pro221Glu; Pro221Phe; Pro221Gly; Pro221His; Pro221Ile; Pro221Lys; Pro221Leu; Pro221Met; Pro221Asn; Pro221Gln; Pro221Arg; Pro221Ser; Pro221Thr; Pro221Val; Pro221Trp; Pro221Tyr; Pro222Ala; Pro222Cys; Pro222Asp; Pro222Glu; Pro222Phe; Pro222Gly; Pro222His; Pro222Ile; Pro222Lys; Pro222Leu; Pro222Met; Pro222Asn; Pro222Gln; Pro222Arg; Pro222Ser; Pro222Thr; Pro222Val; Pro222Trp; Pro222Tyr; Lys223Ala; Lys223Cys; Lys223Asp; Lys223Glu; Lys223Phe; Lys223Gly; Lys223His; Lys223Ile; Lys223Leu; Lys223Met; Lys223Asn; Lys223Pro; Lys223Gln; Lys223Arg; Lys223Ser; Lys223Thr; Lys223Val; Lys223Trp; Lys223Tyr; Gly224Ala; Gly224Cys; Gly224Asp; Gly224Glu; Gly224Phe; Gly224His; Gly224Ile; Gly224Lys; Gly224Leu; Gly224Met; Gly224Asn; Gly224Pro; Gly224Gln; Gly224Arg; Gly224Ser; Gly224Thr; Gly224Val; Gly224Trp; Gly224Tyr; Asp225Ala; Asp225Cys; Asp225Glu; Asp225Phe; Asp225Gly; Asp225His; Asp225Ile; Asp225Lys; Asp225Leu; Asp225Met; Asp225Asn; Asp225Pro; Asp225Gln; Asp225Arg; Asp225Ser; Asp225Thr; Asp225Val; Asp225Trp; Asp225Tyr; Pro226Ala; Pro226Cys; Pro226Asp; Pro226Glu; Pro226Phe; Pro226Gly; Pro226His; Pro226Ile; Pro226Lys; Pro226Leu; Pro226Met; Pro226Asn; Pro226Gln; Pro226Arg; Pro226Ser; Pro226Thr; Pro226Val; Pro226Trp; Pro226Tyr; Val227Ala; Val227Cys; Val227Asp; Val227Glu; Val227Phe; Val227Gly; Val227His; Val227Ile; Val227Lys; Val227Leu; Val227Met; Val227Asn; Val227Pro; Val227Gln; Val227Arg; Val227Ser; Val227Thr; Val227Trp; Val227Tyr; Val228Ala; Val228Cys; Val228Asp; Val228Glu; Val228Phe; Val228Gly; Val228His; Val228Ile; Val228Lys; Val228Leu; Val228Met; Val228Asn; Val228Pro; Val228Gln; Val228Arg; Val228Ser; Val228Thr; Val228Trp; Val228Tyr; Leu229Ala; Leu229Cys; Leu229Asp; Leu229Glu; Leu229Phe; Leu229Gly; Leu229His; Leu229Ile; Leu229Lys; Leu229Met; Leu229Asn; Leu229Pro; Leu229Gln; Leu229Arg; Leu229Ser; Leu229Thr; Leu229Val; Leu229Trp; Leu229Tyr; Ala230Cys; Ala230Asp; Ala230Glu; Ala230Phe; Ala230Gly; Ala230His; Ala230Ile; Ala230Lys; Ala230Leu; Ala230Met; Ala230Asn; Ala230Pro; Ala230Gln; Ala230Arg; Ala230Ser; Ala230Thr; Ala230Val; Ala230Trp; Ala230Tyr; Val231Ala; Val231Cys; Val231Asp; Val231Glu; Val231Phe; Val231
Gly; Val231His; Val231Ile; Val231Lys; Val231Leu; Val231Met; Val231Asn; Val231Pro; Val231Gln; Val231Arg; Val231Ser; Val231Thr; Val231Trp; Val231Tyr; Leu232Ala; Leu232Cys; Leu232Asp; Leu232Glu; Leu232Phe; Leu232Gly; Leu232His; Leu232Ile; Leu232Lys; Leu232Met; Leu232Asn; Leu232Pro; Leu232Gln; Leu232Arg; Leu232Ser; Leu232Thr; Leu232Val; Leu232Trp; Leu232Tyr; Ser233Ala; Ser233Cys; Ser233Asp; Ser233Glu; Ser233Phe; Ser233Gly; Ser233His; Ser233Ile; Ser233Lys; Ser233Leu; Ser233Met; Ser233Asn; Ser233Pro; Ser233Gln; Ser233Arg; Ser233Thr; Ser233Val; Ser233Trp; Ser233Tyr; Ser234Ala; Ser234Cys; Ser234Asp; Ser234Glu; Ser234Phe; Ser234Gly; Ser234His; Ser234Ile; Ser234Lys; Ser234Leu; Ser234Met; Ser234Asn; Ser234Pro; Ser234Gln; Ser234Arg; Ser234Thr; Ser234Val; Ser234Trp; Ser234Tyr; Arg235Ala; Arg235Cys; Arg235Asp; Arg235Glu; Arg235Phe; Arg235Gly; Arg235His; Arg235Ile; Arg235Lys; Arg235Leu; Arg235Met; Arg235Asn; Arg235Pro; Arg235Gln; Arg235Ser; Arg235Thr; Arg235Val; Arg235Trp; Arg235Tyr; Asp236Ala; Asp236Cys; Asp236Glu; Asp236Phe; Asp236Gly; Asp236His; Asp236Ile; Asp236Lys; Asp236Leu; Asp236Met; Asp236Asn; Asp236Pro; Asp236Gln; Asp236Arg; Asp236Ser; Asp236Thr; Asp236Val; Asp236Trp; Asp236Tyr; Lys237Ala; Lys237Cys; Lys237Asp; Lys237Glu; Lys237Phe; Lys237Gly; Lys237His; Lys237Ile; Lys237Leu; Lys237Met; Lys237Asn; Lys237Pro; Lys237Gln; Lys237Arg; Lys237Ser; Lys237Thr; Lys237Val; Lys237Trp; Lys237Tyr; Lys238Ala; Lys238Cys; Lys238Asp; Lys238Glu; Lys238Phe; Lys238Gly; Lys238His; Lys238Ile; Lys238Leu; Lys238Met; Lys238Asn; Lys238Pro; Lys238Gln; Lys238Arg; Lys238Ser; Lys238Thr; Lys238Val; Lys238Trp; Lys238Tyr; Asp239Ala; Asp239Cys; Asp239Glu; Asp239Phe; Asp239Gly; Asp239His; Asp239Ile; Asp239Lys; Asp239Leu; Asp239Met; Asp239Asn; Asp239Pro; Asp239Gln; Asp239Arg; Asp239Ser; Asp239Thr; Asp239Val; Asp239Trp; Asp239Tyr; Ala240Cys; Ala240Asp; Ala240Glu; Ala240Phe; Ala240Gly; Ala240His; Ala240Ile; Ala240Lys; Ala240Leu; Ala240Met; Ala240Asn; Ala240Pro; Ala240Gln; Ala240Arg; Ala240Ser; Ala240Thr; Ala240Val; Ala240Trp; Ala240Tyr; Lys241Ala; Lys241Cys; Lys241Asp; Lys241Glu; Lys241Phe; Lys241Gly; Lys241His; Lys241Ile; Lys241Leu; Lys241Met; Lys241Asn; Lys241Pro; Lys241Gln; Lys241Arg; Lys241Ser; Lys241Thr; Lys241Val; Lys241Trp; Lys241Tyr; Tyr242Ala; Tyr242Cys; Tyr242Asp; Tyr242Glu; Tyr242Phe; Tyr242Gly; Tyr242His; Tyr242Ile; Tyr242Lys; Tyr242Leu; Tyr242Met; Tyr242Asn; Tyr242Pro; Tyr242Gln; Tyr242Arg; Tyr242Ser; Tyr242Thr; Tyr242Val; Tyr242Trp; Asp243Ala; Asp243Cys; Asp243Glu; Asp243Phe; Asp243Gly; Asp243His; Asp243Ile; Asp243Lys; Asp243Leu; Asp243Met; Asp243Asn; Asp243Pro; Asp243Gln; Asp243Arg; Asp243Ser; Asp243Thr; Asp243Val; Asp243Trp; Asp243Tyr; Asp244Ala; Asp244Cys; Asp244Glu; Asp244Phe; Asp244Gly; Asp244His; Asp244Ile; Asp244Lys; Asp244Leu; Asp244Met; Asp244Asn; Asp244Pro; Asp244Gln; Asp244Arg; Asp244Ser; Asp244Thr; Asp244Val; Asp244Trp; Asp244Tyr; Lys245Ala; Lys245Cys; Lys245Asp; Lys245Glu; Lys245Phe; Lys245Gly; Lys245His; Lys245Ile; Lys245Leu; Lys245Met; Lys245Asn; Lys245Pro; Lys245Gln; Lys245Arg; Lys245Ser; Lys245Thr; Lys245Val; Lys245Trp; Lys245Tyr; Leu246Ala; Leu246Cys; Leu246Asp; Leu246Glu; Leu246Phe; Leu246Gly; Leu246His; Leu246Ile; Leu246Lys; Leu246Met; Leu246Asn; Leu246Pro; Leu246Gln; Leu246Arg; Leu246Ser; Leu246Thr; Leu246Val; Leu246Trp; Leu246Tyr; Ile247Ala; Ile247Cys; Ile247Asp; Ile247Glu; Ile247Phe; Ile247Gly; Ile247His; Ile247Lys; Ile247Leu; Ile247Met; Ile247Asn; Ile247Pro; Ile247Gln; Ile247Arg; Ile247Ser; Ile247Thr; Ile247Val; Ile247Trp; Ile247Tyr; Ala248Cys; Ala248Asp; Ala248Glu; Ala248Phe; Ala248Gly; Ala248His; Ala248Ile; Ala248Lys; Ala248Leu; Ala248Met; Ala248Asn; Ala248Pro; Ala248Gln; Ala248Arg; Ala248Ser; Ala248Thr; Ala248Val; Ala248Trp; Ala248Tyr; Glu249Ala; Glu249Cys; Glu249Asp; Glu249Phe; Glu249Gly; Glu249His; Glu249Ile; Glu249Lys; Glu249Leu; Glu249Met; Glu249Asn; Glu249Pro; Glu249Gln; Glu249Arg; Glu249Ser; Glu249Thr; Glu249Val; Glu249Trp; Glu249Tyr; Ala250Cys; Ala250Asp; Ala250Glu; Ala250Phe; Ala250Gly; Ala250His; Ala250Ile; Ala250Lys; Ala250Leu; Ala250Met; Ala250Asn; Ala250Pro; Ala250Gln; Ala250Arg; Ala250Ser; Ala250Thr; Ala250Val; Ala250Trp; Ala250Tyr; Thr251Ala; Thr251Cys; Thr251Asp; Thr251Glu; Thr251Phe; Thr251Gly; Thr251His; Thr251Ile; Thr251Lys; Thr251Leu; Thr251Met; Thr251Asn; Thr251Pro; Thr251Gln; Thr251Arg; Thr251Ser; Thr251Val; Thr251Trp; Thr251Tyr; Lys252Ala; Lys252Cys; Lys252Asp; Lys252Glu; Lys252Phe; Lys252Gly; Lys252His; Lys252Ile; Lys252Leu; Lys252Met; Lys252Asn; Lys252Pro; Lys252Gln; Lys252Arg; Lys252Ser; Lys252Thr; Lys252Val; Lys252Trp; Lys252Tyr; Val253Ala; Val253Cys; Val253Asp; Val253Glu; Val253Phe; Val253Gly; Val253His; Val253Ile; Val253Lys; Val253Leu; Val253Met; Val253Asn; Val253Pro; Val253Gln; Val253Arg; Val253Ser; Val253Thr; Val253Trp; Val253Tyr; Val254Ala; Val254Cys; Val254Asp; Val254Glu; Val254Phe; Val254Gly; Val254His; Val254Ile; Val254Lys; Val254Leu; Val254Met; Val254Asn; Val254Pro; Val254Gln; Val254Arg; Val254Ser; Val254Thr; Val254Trp; Val254Tyr; Met255Ala; Met255Cys; Met255Asp; Met255Glu; Met255Phe; Met255Gly; Met255His; Met255Ile; Met255Lys; Met255Leu; Met255Asn; Met255Pro; Met255Gln; Met255Arg; Met255Ser; M
et255Thr; Met255Val; Met255Trp; Met255Tyr; Lys256Ala; Lys256Cys; Lys256Asp; Lys256Glu; Lys256Phe; Lys256Gly; Lys256His; Lys256Ile; Lys256Leu; Lys256Met; Lys256Asn; Lys256Pro; Lys256Gln; Lys256Arg; Lys256Ser; Lys256Thr; Lys256Val; Lys256Trp; Lys256Tyr; Ala257Cys; Ala257Asp; Ala257Glu; Ala257Phe; Ala257Gly; Ala257His; Ala257Ile; Ala257Lys; Ala257Leu; Ala257Met; Ala257Asn; Ala257Pro; Ala257Gln; Ala257Arg; Ala257Ser; Ala257Thr; Ala257Val; Ala257Trp; Ala257Tyr; Leu258Ala; Leu258Cys; Leu258Asp; Leu258Glu; Leu258Phe; Leu258Gly; Leu258His; Leu258Ile; Leu258Lys; Leu258Met; Leu258Asn; Leu258Pro; Leu258Gln; Leu258Arg; Leu258Ser; Leu258Thr; Leu258Val; Leu258Trp; Leu258Tyr; Asn259Ala; Asn259Cys; Asn259Asp; Asn259Glu; Asn259Phe; Asn259Gly; Asn259His; Asn259Ile; Asn259Lys; Asn259Leu; Asn259Met; Asn259Pro; Asn259Gln; Asn259Arg; Asn259Ser; Asn259Thr; Asn259Val; Asn259Trp; Asn259Tyr; Met260Ala; Met260Cys; Met260Asp; Met260Glu; Met260Phe; Met260Gly; Met260His; Met260Ile; Met260Lys; Met260Leu; Met260Asn; Met260Pro; Met260Gln; Met260Arg; Met260Ser; Met260Thr; Met260Val; Met260Trp; Met260Tyr; Asn261Ala; Asn261Cys; Asn261Asp; Asn261Glu; Asn261Phe; Asn261Gly; Asn261His; Asn261Ile; Asn261Lys; Asn261Leu; Asn261Met; Asn261Pro; Asn261Gln; Asn261Arg; Asn261Ser; Asn261Thr; Asn261Val; Asn261Trp; Asn261Tyr; Gly262Ala; Gly262Cys; Gly262Asp; Gly262Glu; Gly262Phe; Gly262His; Gly262Ile; Gly262Lys; Gly262Leu; Gly262Met; Gly262Asn; Gly262Pro; Gly262Gln; Gly262Arg; Gly262Ser; Gly262Thr; Gly262Val; Gly262Trp; Gly262Tyr; Lys263Ala; Lys263Cys; Lys263Asp; Lys263Glu; Lys263Phe; Lys263Gly; Lys263His; Lys263Ile; Lys263Leu; Lys263Met; Lys263Asn; Lys263Pro; Lys263Gln; Lys263Arg; Lys263Ser; Lys263Thr; Lys263Val; Lys263Trp; Lys263Tyr; Met 264Ala; Met 264Cys; Met 264Asp; Met 264Glu; Met 264Phe; Met 264Gly; Met 264His; Met 264Ile; Met 264Lys; Met 264Leu; Met 264Asn; Met 264Pro; Met 264Gln; Met 264Arg; Met 264Ser; Met 264Thr; Met 264Val; Met 264Trp; Met 264Tyr; Asn 265Ala; Asn 265Cys; Asn 265Asp; Asn 265Glu; Asn 265Phe; Asn 265Gly; Asn 265His; Asn 265Ile; Asn 265Lys; Asn 265Leu; Asn 265Met; ; Asn 265Pro; Asn 265Gln; Asn 265Arg; Asn 265Ser; Asn 265Thr; Asn 265Val; Asn 265Trp; Asn 265Tyr; Gly 266Ala; Gly 266Cys; Gly 266Asp; Gly 266Glu; Gly 266Phe; ; Gly 266His; Gly 266Ile; Gly 266Lys; Gly 266Leu; Gly 266Met; Gly 266Asn; Gly 266Pro; Gly 266Gln; Gly 266Arg; Gly 266Ser; Gly 266Thr; Gly 266Val; Gly 266Trp; Gly 266Tyr; Lys267Ala; Lys267Cys; Lys267Asp; Lys267Glu; Lys267Phe; Lys267Gly; Lys267His; Lys267Ile; Lys267Leu; Lys267Met; Lys267Asn; Lys267Pro; Lys267Gln; Lys267Arg; Lys267Ser; Lys267Thr; Lys267Val; Lys267Trp; および Lys267Tyr.
配列番号:5
EMKDDFAKLEEQFDAKLGIFALDTGTNRTVAYRPDERFAFASTIKALTVGVLLQQKSIEDLNQRITTRDDLVNYNPITEKHVDTGMTLKELADASLRYSDNAAQNLILKQIGGPESLKKELRKIGDEVTNPERFEPELNEVNPGETQDTSTARALVTSLRAFALEDKLPSEKRELLIDWMKRNTTGDALIRAGVPDGWEVGDKTGSGDYGTRNDIAIIWPPKGDPVVLAVLSSRDKKDAKYDNKLIAEATKVVMKALNMNGK
または
配列番号6:信号配列およびQASKTアミノ酸の付加を含む配列番号5(コード領域は下線付き):
配列番号:7
A232G、A237S、A238G、S240D、およびD276N変異体、Hind III部位(AAGCTTは太字)ならびに追加のKおよびTアミノ酸の完全ヌクレオチド配列。リーダーおよび追加のヌクレオチド(Hind III部位ならびにKおよびTアミノ酸−アミノ酸配列QASKTの付加用)には下線を引いている。
SOEもしくはQUIKCHANGE Multi Site−Directed Mutagenesis Kit(Stratagene,CA,USA)を使った部位特異的変異誘発により、またはGeneMorph(登録商標)II Random Mutagenesis Kit(Stratagene,CA,USA)を使ったランダム変異誘発により種々のP1A変異体を作製した。変異DNAを細菌、大腸菌または枯草菌に形質転換し、これをセフォタキシム(部位特異的な変異体)またはセフトリアキソン(ランダム変異体)について検査した。ニトロセフィン試験によりコロニー中のβ−ラクタマーゼの存在をさらに確認し、陽性のコロニーをさらなる分析用に選別した。変異体β−ラクタマーゼのDNA配列をシーケンシングにより確認した。
第1日目に、10μg/mlのカナマイシンを含むLB寒天プレート上で、少量の凍結IS288バチルス・ズブチリス細胞の画線培養を行った。翌朝、単独培養物をこのプレートから採取し、振とうフラスコ培養のために10X3mlの最小増殖培地中に播種した。同日午後に、100mlの一晩(o/n)培養物で出発OD600が0.01となる一定容量を3mlの前培養液から採取した。100mlの培養液を振とう器中、+37℃で一晩インキュベートした。数個の3ml前培養液から、OD600=1グリセリンストック(10%グリセリン)を作製した。グリセリンストックを−70℃で保存した。
バチルス・ズブチリスの振とうフラスコ培養中に、種々の時点で試料を採取し、IS288の産生レベルを評価した。さらに細胞がどの程度増殖しているかを調べるために、各時点でOD600値を測定した。製造されるタンパク質の量をSDS−PAGEで推定した。
この調査で用いられた抗生物質は、例えば、静脈内投与によるセファロスポリンを選択した。理論に束縛されることを意図するものではないが、選択された抗生物質の濃度は、文献で報告された胆汁または十二指腸中の濃度に出来る限り近い濃度とした。この実験はまた、様々なpHで行われた。
異なる量の精製酵素をヒト回腸キームス中、適切な温度で設定した時間、インキュベートした。種々の時点で試料を採取した。IS288の分解パターンをSDS−PAGEで解析し、IS288の活性をニトロセフィンを基質として使用して分析した。
変異設計は、特に、次の構造データ(例えば、結晶構造データ、相同体モデル、など): P1A結晶構造(Knox and Moews,J.Mol Biol.,220,435−455(1991))、CTX−M−44(1BZA(Ibuka et al.Journal of Molecular Biology Volume 285,Issue 5 2079−2087(1999))、1IYS(1BZA(Ibuka et al.Journal of Molecular Biology Volume 285,Issue 5 2079−2087(1999))、1IYS(Ibuka et al.Biochemistry,2003,42(36):10634−43)、1IYO、1IYPおよび1IYQ(Shimamura et al.2002 J.Biol.Chem. 277:46601−08)、プロテウス・ブルガリスK1(1HZO,Nugaka et al.J Mol Biol.2002 Mar 15;317(1):109−17)およびプロテウス・ペンネリHugA(Liassine et al.Antimicrob Agents Chemother.2002 Jan;46(1):216−9.2002)、また、Bonnet,Antimicrob.Agents Chemother 48(1):1−14(2004)(CTM−Xに対して)中で概説されている)をベースにした。全てのこれらの文献の内容は参照によりその全体が本明細書に組み込まれる。いくつかの実施形態では、本変異は次のβ−ラクタマーゼのいずれか1種の構造データ(例えば、結晶構造データ、相同体モデル、など)から情報を得ている:P1A、P2A、P3A、CTX−M−3、CTX−M−4、CTX−M−5、CTX−M−9、CTX−M−10、CTX−M−14、CTX−M−15、CTX−M−16、CTX−M−18、CTX−M−19、CTX−M−25、CTX−M−26、CTX−M−27、CTX−M−32、CTX−M−44、CTX−M−45、およびCTX−M−54。このような情報は当業者により既知のデータベース、例えば、Swiss−Prot Protein Sequence Data Bank、NCBI、およびPDBで入手可能である。
I72S、Q135MおよびT160Fを含む変異の第1のブロックをQUIKCHANGE Multi Site−Directed変異誘発キット(以降では略してMultiキットと呼ぶ)を使った1つの反応で変異誘発性プライマー中に導入した。penP遺伝子を保持するプラスミドを変異誘発反応におけるテンプレートとして使用した。変異体一本鎖プラスミドを大腸菌XL10Gold中に形質転換し、カナマイシン/クロラムフェニコールで選択した。コンピテントXL10 Gold細胞をMultiキットと共に入手した。コロニー(10〜30)を採取し、ニトロセフィンで試験し、β−ラクタマーゼ活性を確認した。コロニーの一部をPCRのテンプレートとして使って、得られた断片が不純物を含まない場合は、それをDNA塩基配列決定に移した。残りのコロニーを適切な抗生物質を補充したルリア培地中で一晩、37℃で培養し、一部の培養液をグリセリン中(≦10%、最終)で保存し、別の一部をプラスミド単離に使用した。目的の変異がDNA塩基配列決定法で確認された後、変異体クローンをさらに詳細に特徴付けた。周辺質ライセートを調製し、SDS PAGEで分析して、セフォタキシム加水分解の動力学を分光測定により測定した。
P1AのB3β−鎖の標的アミノ酸は相互に非常に近くに位置しているので、少なくとも1ラウンドにおいてはMulti−Siteプロトコルは適さない。その代わりに、SOE技術を使って4つ全てのアミノ酸が交換された。交換を含む領域は、24ヌクレオチド(8個のアミノ酸コドン)を含み、2つのPCRプライマーの重複伸張部分中に含まれた。変異penP遺伝子を、プライマーA+BおよびC+Dを使って、最初に2つの部分でPCRした(図7)。その後、2つのPCR産物を合わせ、penP遺伝子の5’および3’部分に相補的な、プライマーAおよびDを使って増幅した。クローニング部位はプライマーAおよびDに含めた。構築物の準備ができると、Multiキットを使って、さらなる変異を加えた。
これらの変異は、Multi−Siteキット技術を使い、以前に作成した変異体プラスミドを鋳型として使って加えた。作成した変異のリストを表1に示す。変異の組み合わせの数は容易に増やせるので、個々のクローンのセフォタキシム分解動力学の測定よりもさらに堅牢な方法を使って特徴付けを行った。一次特徴付けは、セフォタキシムMICの決定であった。
理論に束縛されることを意図するものではないが、P1Aのセフォタキシム、セフトリアキソンおよびセフロキシムに対し測定した動力学的パラメータから、P1Aは固有の低いセファロスポリナーゼ活性を有することが推定される。全体的に、変異体のリガンドに対する親和性は、増加した(すなわち、Kmが減少した)。IS229(ブロック2+R244T)変異体ではVmaxが増加し、親和性が減少した(Kmが増加した)(表5)。IS229に対しては、Kcatが最も大きく増加した。
枯草菌増殖条件中の変異体の安定性を試験するために、RS310、IS219およびIS232の振とうフラスコ培養を行った。培養を5g/lおよび10g/lの2つの異なるグルコース濃度で行った。
精製の結果を溶出ピーク図(図3、4および5)およびタンパク質濃度として、ピークテーブルとして、ならびにSDS−PAGE図(図6)として示す。
疎水性相互作用クロマトグラフィー(HIC)を3つの別々の場合について、異なるパラメータを用いて実行した。
第1のラン(16.10.08、図3)では、試料体積を約50ml、通過画分の体積を5ml、非結合試料用の洗浄体積を2CV、および溶出画分の体積を1.0mlとした。その後のHICラン(4.11.08、図4)では、試料体積を65mlに、通過画分体積を10mlに、非結合試料用洗浄体積を3CVに、および画分の大きさを1.5mlに増やした。最後のラン(12.11.08、図5)では、試料体積および非結合試料用洗浄体積が前のランと異なり、それぞれ125mlおよび4CVとした。
それぞれの精製物から、1つ、2つまたは3つの通過画分ならびに溶出タンパク質ピークを含む全画分を濃縮のために選択した。選択試料を表8に示す。表中には、その試料の出発体積ならびに最終体積および濃縮係数も示した。
6.5μlを加えたB1121108を除いて、最大体積(17.5μl)の硫酸アンモニウム濾液および通過画分をSDS−PAGEに加えた(図6)。レーン当たり約0.5μgのタンパク質になるように、また、試料中の全てのタンパク質がP1A誘導体IS288であると仮定して、タンパク質ピークからの試料の体積を計算した。SDS−PAGEを図6に示した。
P1Aβ−ラクタマーゼの非存在下および存在下で、大腸菌に対するアンピシリンおよびセフトリアキソンの50%有効阻害濃度(EC50)を決定した。これらの調査においては、示した有効濃度は、実験の最初に加えられたアンピシリンまたはセフトリアキソンの初期濃度であって、実験の過程でまたはインキュベーション期間の最後に測定された濃度ではない。分析の結果を表12〜14に示す。
高抗生物質濃度の存在下で腸中のβ−ラクタマーゼの活性を模倣するように設計されたマイクロタイタープレート活性アッセイにより、P1AおよびP4Aを、アンピシリン、セフトリアゾン、セフォタキシム、セファゾリン、セフロキシム、セフォペラゾン、セフェピム、およびセフタジジムの分解について検査した。10、100または1000μg/mlの示した抗生物質と、10または100ng/mlの濃度のP1AまたはP4Aを混合することにより、アッセイを行った。プレートを37℃で1時間インキュベートした後に大腸菌(ATCC25922)を加えた、またはβ−ラクタマーゼ酵素の添加直後に大腸菌を添加した。プレートを一晩インキュベートし、Spectramax384Plusプレートリーダーで625nmの吸光度(OD625)を測定することにより、細菌増殖を定量化した。それぞれのβ−ラクタマーゼおよび抗生物質に対し、分析を2回行った。培養上清のβ−ラクタマーゼ活性を、個々のウエル中の細菌増殖の外観に基づいて、陽性または陰性として判定した。1.0以上のOD625は最大細菌増殖を示し、したがって、完全な抗生物質分解および高β−ラクタマーゼ活性を示した。1.0未満のOD625は低細菌増殖を示し、したがって、不完全な抗生物質分解、すなわち、低β−ラクタマーゼ活性を示した。
次の定義は、本明細書で開示の本発明との関連で使用される。特に断らなければ、本明細書で使用される全ての技術用語および科学用語は、本発明が属する分野の当業者に一般的に理解されるのと同じ意味を有する。
本発明をその特定の実施形態と関連付けて説明してきたが、その実施形態はさらに修正が可能であり、本出願は、一般的に、本発明の原理に従った本発明の任意の変形、使用、または改変を包含することが意図され、本発明が属する技術内の既知のまたは日常的な実施の範囲に入る、および本明細書に示されるおよび以下の添付の請求項の範囲に入る本質的な特徴に該当し得る本開示からの乖離を含むものと理解されよう。
参照による組み込み
Claims (73)
- 配列番号1と少なくとも70%の配列同一性を有し、Ambler分類による1つまたは複数の次の変異:F33X、Q135X、G156X、A232X、A237X、A238X、S240X、T243X、R244X、S266X、およびD276Xを有するアミノ酸配列含むβ−ラクタマーゼであって、Xが任意の天然アミノ酸であり、但し、単一変異体の場合にはD276Xが存在しない、β−ラクタマーゼ。
- Xが親水性または疎水性のアミノ酸残基である、請求項1に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アルギニン(R)およびリシン(K)から選択される極性で正電荷の親水性残基またはヒスチジン(H)を含む芳香族の極性で正電荷の親水性残基である、請求項1または2に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン(N)、グルタミン(Q)、セリン(S)、トレオニン(T)、プロリン(P)、およびシステイン(C)から選択される極性で中性電荷の親水性残基である、請求項1〜3のいずれか1項に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン酸(D)およびグルタミン酸(E)から選択される極性で負電荷の親水性残基である、請求項1〜4のいずれか1項に記載のβ−ラクタマーゼ。
- 前記疎水性のアミノ酸残基が、グリシン(G)、アラニン(A)、ロイシン(L)、イソロイシン(I)、メチオニン(M)、およびバリン(V)から選択される疎水性の脂肪族アミノ酸、またはフェニルアラニン(F)、トリプトファン(W)、およびチロシン(Y)から選択される疎水性の芳香族アミノ酸である、請求項1〜5のいずれか1項に記載のβ−ラクタマーゼ。
- 配列番号1と少なくとも約70%の配列同一性を有し、1つまたは複数のAmbler分類による以下の変異:
位置33に、フェニルアラニン(F)以外の疎水性の残基;
位置135に、グルタミン(Q)以外の疎水性の残基;
位置156に、グリシン(G)以外の親水性の残基;
位置232に、アラニン(A)以外の疎水性の残基;
位置237に、アラニン(A)以外の親水性の残基;
位置238に、アラニン(A)以外の疎水性または親水性の残基;
位置240に、セリン(S)以外の親水性の残基;
位置243に、トレオニン(T)以外の疎水性の残基;
位置244に、アルギニン(R)以外の疎水性の残基;
位置266に、セリン(S)以外の親水性の残基;および
位置276に、アスパラギン酸(D)以外の親水性の残基を有するアミノ酸配列を含むβ−ラクタマーゼであって、
但し、単一変異体の場合には、位置276に対応する位置に、アスパラギン酸(D)以外の親水性のアミノ酸残基は存在しない、β−ラクタマーゼ。 - 前記親水性のアミノ酸残基が、アルギニン(R)およびリシン(K)から選択される極性で正電荷の親水性残基またはヒスチジン(H)を含む芳香族の極性で正電荷の親水性残基である、請求項1〜7のいずれか1項に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン(N)、グルタミン(Q)、セリン(S)、トレオニン(T)、プロリン(P)、およびシステイン(C)から選択される極性で中性電荷の親水性残基である、請求項1〜8のいずれか1項に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン酸(D)およびグルタミン酸(E)から選択される極性で負電荷の親水性残基である、請求項1〜9のいずれか1項に記載のβ−ラクタマーゼ。
- 前記疎水性のアミノ酸が、グリシン(G)、アラニン(A)、ロイシン(L)、イソロイシン(I)、メチオニン(M)、およびバリン(V)から選択される疎水性の脂肪族アミノ酸、またはフェニルアラニン(F)、トリプトファン(W)、およびチロシン(Y)から選択される疎水性の芳香族アミノ酸である、請求項1〜10のいずれか1項に記載のβ−ラクタマーゼ。
- Ambler分類による位置に1つまたは複数の次の変異:F33Y、Q135M、G156R、A232G、A237S、A238GまたはT、S240PまたはD、T243I、R244T、S266N、D276NまたはRまたはKを含み、但し、単一変異体の場合には、D276NまたはRまたはKは存在しない、請求項1〜11のいずれか1項に記載のβ−ラクタマーゼ。
- Q135Mを含む、請求項1〜12のいずれか1項に記載のβ−ラクタマーゼ。
- G156RおよびA238Tを含む、請求項1〜13のいずれか1項に記載のβ−ラクタマーゼ。
- F33YおよびD276Nを含む、請求項1〜14のいずれか1項に記載のβ−ラクタマーゼ。
- F33Y、S240P、およびD276Nを含む、請求項1〜15のいずれか1項に記載のβ−ラクタマーゼ。
- F33Y、A238T、およびD276Nを含む、請求項1〜16のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、およびS240Dを含む、請求項1〜17のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびR244Tを含む、請求項1〜18のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびD276Rを含む、請求項1〜19のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびD276Kを含む、請求項1〜20のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびQ135Mを含む、請求項1〜21のいずれか1項に記載のβ−ラクタマーゼ。
- A238Tを含む、請求項1〜22のいずれか1項に記載のβ−ラクタマーゼ。
- T243I、S266N、およびD276Nを含む、請求項1〜23のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびD276Nを含む、請求項1〜24のいずれか1項に記載のβ−ラクタマーゼ。
- 配列番号1と少なくとも約70%の配列同一性を有し、Ambler分類による:
位置232に、アラニン(A)以外の疎水性の残基;
位置237に、アラニン(A)以外の親水性の残基;
位置238に、アラニン(A)以外の疎水性の残基;
位置240に、セリン(S)以外の親水性の残基;および
位置276に、アスパラギン酸(D)以外の親水性の残基を有するアミノ酸配列を含むβ−ラクタマーゼ。 - 前記親水性のアミノ酸残基が、アルギニン(R)およびリシン(K)から選択される極性で正電荷の親水性残基またはヒスチジン(H)を含む芳香族の極性で正電荷の親水性残基である、請求項26に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン(N)、グルタミン(Q)、セリン(S)、トレオニン(T)、プロリン(P)、およびシステイン(C)から選択される極性で中性電荷の親水性残基である、請求項26または27に記載のβ−ラクタマーゼ。
- 前記親水性のアミノ酸残基が、アスパラギン酸(D)およびグルタミン酸(E)から選択される極性で負電荷の親水性残基である、請求項26〜28のいずれか1項に記載のβ−ラクタマーゼ。
- 前記疎水性のアミノ酸が、グリシン(G)、アラニン(A)、ロイシン(L)、イソロイシン(I)、メチオニン(M)、およびバリン(V)から選択される疎水性の脂肪族アミノ酸、またはフェニルアラニン(F)、トリプトファン(W)、およびチロシン(Y)から選択される疎水性の芳香族アミノ酸である、請求項26〜29のいずれか1項に記載のβ−ラクタマーゼ。
- 位置232のアラニン(A)以外の前記疎水性の残基が、グリシン(G)である、請求項26〜30のいずれか1項に記載のβ−ラクタマーゼ。
- 位置237のアラニン(A)以外の前記親水性の残基が、セリン(S)である、請求項26〜31のいずれか1項に記載のβ−ラクタマーゼ。
- 位置238のアラニン(A)以外の前記疎水性の残基が、グリシン(G)である、請求項26〜32のいずれか1項に記載のβ−ラクタマーゼ。
- 位置240のセリン(S)以外の前記親水性の残基が、アスパラギン酸(D)である、請求項26〜33のいずれか1項に記載のβ−ラクタマーゼ。
- 位置276のアスパラギン酸(D)以外の前記親水性の残基が、アスパラギン(N)である、請求項26〜34のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびD276Nの内の1つまたは複数を含む、請求項26〜35のいずれか1項に記載のβ−ラクタマーゼ。
- A232G、A237S、A238G、S240D、およびD276Nを含む、請求項26〜36のいずれか1項に記載のβ−ラクタマーゼ。
- 請求項1〜37のいずれか1項に記載のβ−ラクタマーゼをコードするポリヌクレオチド配列を含むポリヌクレオチド。
- 請求項38に記載のポリヌクレオチドを含む宿主細胞。
- ペニシリンおよびセファロスポリンの内の1つまたは複数を加水分解する、請求項1〜39のいずれか1項に記載のβ−ラクタマーゼ。
- 前記セファロスポリンが、セフォペラゾン、セフトリアキソンまたはセファゾリンから選択される、請求項40に記載のβ−ラクタマーゼ。
- セファロスポリンに対し低KMを有することを特徴とする、請求項1〜41のいずれか1項に記載のβ−ラクタマーゼ。
- 前記低いKMが、約500μM、または約100μM、または約10μM、または約1μM、または約0.1μM、または約0.01μM未満である、請求項42に記載のβ−ラクタマーゼ。
- 高Vmaxを有することを特徴とする、請求項1〜43のいずれか1項に記載のβ−ラクタマーゼ。
- 前記高Vmaxが、約100s−1、または約1000s−1、または約10000s−1、または約100000s−1、または約1000000s−1を超える、請求項344に記載のβ−ラクタマーゼ。
- 配列番号1と比較して、セファロスポリンに対して改善された触媒効率を有することを特徴とする、請求項1〜45のいずれか1項に記載のβ−ラクタマーゼ。
- 前記触媒効率が、約106M−1s−1より大きい、請求項46に記載のβ−ラクタマーゼ。
- 前記GI管中で活性であることを特徴とする、請求項1〜47のいずれか1項に記載のβ−ラクタマーゼ。
- 小腸中で、任意選択で、十二指腸、空腸、および回腸から選択される1つまたは複数の器官中で安定である、請求項48に記載のβ−ラクタマーゼ。
- 小腸中でプロテアーゼに対し耐性があることを特徴とする、請求項1〜49のいずれか1項に記載のβ−ラクタマーゼ。
- 約6.0〜約7.5のpHで実質的に活性であることを特徴とする、請求項1〜50のいずれか1項に記載のβ−ラクタマーゼ。
- 任意選択で、タゾバクタム、スルバクタム、およびクラブラン酸から選択される1つまたは複数のβ−ラクタマーゼ阻害剤に対して耐性があることを特徴とする、請求項1〜51のいずれか1項に記載のβ−ラクタマーゼ。
- 請求項1〜52のいずれか1項に記載のβ−ラクタマーゼおよび1種または複数種の薬学的に許容可能なキャリアまたは賦形剤を含む、医薬組成物。
- 任意選択で、タブレットまたは多粒子含有スプリンクル、および多粒子含有カプセルとして、経口投与用に処方される、請求項53に記載の医薬組成物。
- 追加の抗生物質分解酵素をさらに含む、請求項1〜54のいずれか1項に記載の医薬組成物。
- 前記抗生物質酵素が、クラスEC3.5.2.6のものである、請求項55に記載の医薬組成物。
- 前記抗生物質分解酵素が、機能グループ1、グループ2、グループ3、またはグループ4β−ラクタマーゼおよび/または分子/AmblerクラスA、またはクラスB、またはクラスC、またはクラスDβ−ラクタマーゼから選択される、請求項55または56に記載の医薬組成物。
- 前記β−ラクタマーゼが、セリンβ−ラクタマーゼまたは亜鉛依存性(EDTA阻害)β−ラクタマーゼである、請求項55〜57のいずれか1項に記載の医薬組成物。
- 前記β−ラクタマーゼが、P1AまたはP3Aの内の1種または複数種である、請求項55〜58のいずれか1項に記載の医薬組成物。
- 前記β−ラクタマーゼが、任意選択で、TEM、SHV、CTX−M、OXA、PER、VEB、GES、およびIBCβ−ラクタマーゼから選択される広域性β−ラクタマーゼ(ESBL)である、請求項55〜59のいずれか1項に記載の医薬組成物。
- 前記β−ラクタマーゼが、任意選択で、AmpC型β−ラクタマーゼ、カルバペネマーゼ、IMP型カルバペネマーゼ(メタロ−β−ラクタマーゼ)、VIM(ベローナインテグロンにコードされたメタロ−β−ラクタマーゼ)、OXA(オキサシリナーゼ)グループのβ−ラクタマーゼ、KPC(肺炎桿菌カルバペネマーゼ)、CMY(クラスC)、SME、IMI、NMCおよびCcrA、ならびにNDM−1(ニューデリー・メタロベータラクタマーゼ)β−ラクタマーゼから選択される阻害剤耐性β−ラクタマーゼである、請求項55〜60のいずれか1項に記載の医薬組成物。
- 前記GI管中の抗生物質誘発性有害作用を処置または予防するための方法であって、有効量の請求項1〜61のいずれか1項に記載の組成物を、それを必要としている患者に投与することを含む方法。
- クロストリジウム・ディフィシレ感染症(CDI)および/またはクロストリジウム・ディフィシレ関連疾患を処置または予防するための方法であって、有効量の請求項1〜61のいずれか1項に記載の組成物を、それを必要としている患者に投与することを含む方法。
- 前記抗生物質誘発性有害作用および/またはCDIまたはクロストリジウム・ディフィシレ関連疾患が、抗生物質関連下痢、クロストリジウム・ディフィシレ下痢(CDD)、クロストリジウム・ディフィシレ炎症性腸疾患、大腸炎、偽膜性大腸炎、発熱、腹痛、脱水および電解質障害、巨大結腸症、腹膜炎、および前記結腸の穿孔および/または破裂の内の1つまたは複数である、請求項62または63に記載の方法。
- 前記CDIおよび/またはクロストリジウム・ディフィシレ関連疾患が、初期発症または再燃の状況において処置される、請求項62〜64のいずれか1項に記載の方法。
- セフトリアキソン関連有害作用を処置または予防する、請求項62〜65のいずれか1項に記載の方法。
- 院内感染症および/または2次新興感染症を処置または予防する、請求項62〜66のいずれか1項に記載の方法。
- 前記患者が、1種または複数種の一次抗生物質による処置をうけている、または最近処置を受けたことがある、請求項62〜67のいずれか1項に記載の方法。
- 前記β−ラクタマーゼが、前記GI管中の過剰な抗生物質残留物を加水分解する、請求項62〜68のいずれか1項に記載の方法。
- 前記β−ラクタマーゼが、患者の前記GI管中の正常な腸内微生物叢を維持し、かつ/または1種または複数種の病原微生物の異常増殖を防止する、請求項62〜69のいずれか1項に記載の方法。
- 前記β−ラクタマーゼが、一次抗生物質の血漿中レベルを実質的に妨げない、請求項62〜70のいずれか1項に記載の方法。
- 初期療法剤および/または補助的療法剤が患者に投与される、請求項62〜71のいずれか1項に記載の方法。
- 前記初期療法剤および/または補助的療法剤が、メトロニダゾール、バンコマイシン、フィダキソマイシン、リファキシミン、糞便細菌療法剤、プロバイオティック療法剤、および抗体治療剤の内の1種または複数種である、請求項62〜72のいずれか1項に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461980844P | 2014-04-17 | 2014-04-17 | |
US61/980,844 | 2014-04-17 | ||
US201462046627P | 2014-09-05 | 2014-09-05 | |
US62/046,627 | 2014-09-05 | ||
PCT/US2015/026457 WO2015161243A2 (en) | 2014-04-17 | 2015-04-17 | Beta-lactamases with improved properties for therapy |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019220462A Division JP7038094B2 (ja) | 2014-04-17 | 2019-12-05 | 治療用として改善された特性を有するβ-ラクタマーゼ |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017515466A true JP2017515466A (ja) | 2017-06-15 |
JP2017515466A5 JP2017515466A5 (ja) | 2018-05-31 |
JP6685925B2 JP6685925B2 (ja) | 2020-04-22 |
Family
ID=54321063
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016562248A Active JP6685925B2 (ja) | 2014-04-17 | 2015-04-17 | 治療用として改善された特性を有するβ−ラクタマーゼ |
JP2019220462A Active JP7038094B2 (ja) | 2014-04-17 | 2019-12-05 | 治療用として改善された特性を有するβ-ラクタマーゼ |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019220462A Active JP7038094B2 (ja) | 2014-04-17 | 2019-12-05 | 治療用として改善された特性を有するβ-ラクタマーゼ |
Country Status (10)
Country | Link |
---|---|
US (14) | US9290754B2 (ja) |
EP (1) | EP3132033B1 (ja) |
JP (2) | JP6685925B2 (ja) |
KR (1) | KR102360582B1 (ja) |
CN (1) | CN106163546B (ja) |
AU (1) | AU2015247382B2 (ja) |
BR (1) | BR112016023360B1 (ja) |
CA (1) | CA2942971C (ja) |
RU (1) | RU2678124C2 (ja) |
WO (1) | WO2015161243A2 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6672277B2 (ja) | 2014-10-08 | 2020-04-01 | シンセティック・バイオロジクス・インコーポレイテッド | ベータラクタマーゼ製剤およびその使用 |
AU2016229976B2 (en) * | 2015-03-06 | 2021-11-11 | Theriva Biologics, Inc. | Safe and effective beta-lactamase dosing for microbiome protection |
BR112018016889A2 (pt) * | 2016-02-23 | 2019-02-12 | Da Volterra | variantes de beta-lactamase |
WO2017144495A1 (en) * | 2016-02-23 | 2017-08-31 | Da Volterra | Beta-lactamase variants |
EP3474885B8 (en) * | 2016-06-28 | 2023-06-21 | Theriva Biologics, Inc. | Microbiome protection from oral antibiotics |
KR20210040395A (ko) | 2018-08-05 | 2021-04-13 | 다 볼떼라 | 이식편 대 숙주 질환의 치료를 위한 조성물 |
EP3829637A1 (en) | 2018-08-05 | 2021-06-09 | Da Volterra | Method for improving anticancer agent efficacy |
CN109337889B (zh) * | 2018-12-26 | 2020-10-02 | 广州白云山拜迪生物医药有限公司 | 一种酶活提高的金属β-内酰胺酶突变体及其构建方法 |
CN109576250A (zh) * | 2018-12-26 | 2019-04-05 | 广州白云山拜迪生物医药有限公司 | 一种酶活提高的头孢菌素酶突变体及其构建方法 |
KR20220006072A (ko) * | 2019-05-06 | 2022-01-14 | 신세틱 바이오로직스, 인코퍼레이티드 | 이식편대숙주병의 치료를 위한 베타-락타마제 조성물 |
EP4148136A1 (en) | 2021-09-08 | 2023-03-15 | Da Volterra | An engineered yeast cell for the delivery of antibiotic-inactivating enzymes |
WO2024012487A1 (en) * | 2022-07-14 | 2024-01-18 | The Hong Kong Polytechnic University | Biosensor comprising a modified beta-lactamase and uses thereof |
CN115433701B (zh) * | 2022-11-08 | 2023-03-17 | 南京农业大学 | 一株变形杆菌及其菌剂和在降解头孢类抗生素中的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013529905A (ja) * | 2010-05-24 | 2013-07-25 | プレヴァブ アール エルエルシー | 改変型β−ラクタマーゼ並びにそれに関する方法及び使用 |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL197650A (ja) | 1954-05-29 | |||
US2941995A (en) | 1957-08-02 | 1960-06-21 | Beecham Res Lab | Recovery of solid 6-aminopenicillanic acid |
US2982696A (en) | 1959-05-01 | 1961-05-02 | Schenley Ind Inc | Ion-exchange procedures for the purification of penicillinase |
US3070511A (en) | 1960-02-10 | 1962-12-25 | Lepetit Spa | Process for preparing 6-aminopenicillanic acid |
US3150059A (en) | 1962-12-26 | 1964-09-22 | Lilly Co Eli | Penicillin deacylation via actinoplanaceae fermentation |
US3239394A (en) | 1964-06-15 | 1966-03-08 | Merck & Co Inc | Process for producing 7-amino-cephalosporanic acid |
US3499909A (en) | 1966-05-18 | 1970-03-10 | Koninklijke Gist Spiritus | Process for production of 6-aminopenicillanic acid |
US3488729A (en) | 1966-08-22 | 1970-01-06 | Lilly Co Eli | Cephalothin ester |
GB1241844A (en) | 1968-08-23 | 1971-08-04 | Beecham Group Ltd | Penicillins |
FI59265C (fi) | 1974-08-13 | 1981-07-10 | Beecham Group Ltd | Foerfarande foer framstaellning av 6-aminopenicillansyra |
GB1463513A (en) | 1974-08-13 | 1977-02-02 | Beecham Group Ltd | Enzymes |
GB2199582A (en) | 1987-01-07 | 1988-07-13 | Bayer Ag | Analogues of pancreatic secretory trypsin inhibitor |
FR2613624B1 (fr) | 1987-04-10 | 1990-11-23 | Roussy Inst Gustave | Composition pharmaceutique, administrable par voie orale, destinee a reduire les effets des b-lactamines |
CA2007083A1 (en) | 1989-01-09 | 1990-07-09 | Nobuhiko Katunuma | Pharmaceutical use of trypstatin |
CS275231B2 (en) | 1989-09-29 | 1992-02-19 | Ustav Makormolekularni Chemie | Medicine bottle |
FI920206A0 (fi) | 1992-01-17 | 1992-01-17 | Pekka Untamo Heino | Medicinsk anvaendning, medicinskt foerfarande och preparat. |
JPH11509096A (ja) | 1995-07-07 | 1999-08-17 | ノボ ノルディスク アクティーゼルスカブ | 胞子形成できないバチルスを用いるタンパク質の生産 |
CN1363680A (zh) * | 2001-01-05 | 2002-08-14 | 上海博德基因开发有限公司 | 一种新的多肽——β内酰胺酶20.24和编码这种多肽的多核苷酸 |
EP1391502B1 (en) | 2001-05-29 | 2012-04-25 | Kao Corporation | Host microorganisms |
FI112666B (fi) | 2001-11-06 | 2003-12-31 | Ipsat Therapies Oy | Itiöimätön Bacillus subtilis, sen valmistus ja käyttö |
FR2843302B1 (fr) | 2002-08-09 | 2004-10-22 | Centre Nat Rech Scient | Forme galenique pour la delivrance colique de principes actifs |
US7494798B2 (en) * | 2004-01-09 | 2009-02-24 | Novozymes, Inc. | Bacillus licheniformis chromosome |
EP1564286A1 (en) * | 2004-02-11 | 2005-08-17 | Université de Liège | Hybrid proteins of beta-lactamase class A |
DE102004032995A1 (de) * | 2004-07-08 | 2006-03-30 | Henkel Kgaa | Neue, sekretierte Genprodukte von Bacillus licheniformis und darauf aufbauende verbesserte biotechnologische Produktionsverfahren |
CN101257892B (zh) | 2005-05-18 | 2013-01-02 | 达沃尔泰拉公司 | 吸附剂的结肠递送 |
FI119190B (fi) | 2006-06-21 | 2008-08-29 | Ipsat Therapies Oy | Modifioitu beta-laktamaasi ja menetelmä sen valmistamiseksi |
CN101104858A (zh) * | 2006-07-10 | 2008-01-16 | 温州医学院 | 一种体外定向进化获取高活力超广谱β-内酰胺酶的方法 |
FI119678B (fi) | 2006-11-28 | 2009-02-13 | Ipsat Therapies Oy | Beta-laktamaasin käyttö |
WO2008066931A2 (en) * | 2006-11-29 | 2008-06-05 | Novozymes, Inc. | Bacillus licheniformis chromosome |
CN101647022B (zh) * | 2007-01-31 | 2012-07-18 | 麦科罗医药科技(武汉)有限公司 | 描述蛋白质的构象和根据折叠、整体形状与结构序列对其进行评价的方法、系统及装置 |
WO2013188578A1 (en) * | 2012-06-12 | 2013-12-19 | The Johns Hopkins University | Efficient, expansive, user-defined dna mutagenesis |
-
2015
- 2015-04-17 EP EP15780157.2A patent/EP3132033B1/en active Active
- 2015-04-17 WO PCT/US2015/026457 patent/WO2015161243A2/en active Application Filing
- 2015-04-17 CN CN201580019029.7A patent/CN106163546B/zh active Active
- 2015-04-17 CA CA2942971A patent/CA2942971C/en active Active
- 2015-04-17 KR KR1020167027846A patent/KR102360582B1/ko active IP Right Grant
- 2015-04-17 AU AU2015247382A patent/AU2015247382B2/en active Active
- 2015-04-17 BR BR112016023360-3A patent/BR112016023360B1/pt active IP Right Grant
- 2015-04-17 JP JP2016562248A patent/JP6685925B2/ja active Active
- 2015-04-17 US US14/689,877 patent/US9290754B2/en active Active
- 2015-04-17 RU RU2016140627A patent/RU2678124C2/ru active
-
2016
- 2016-02-09 US US15/019,474 patent/US9376673B1/en active Active
- 2016-05-20 US US15/160,669 patent/US9404103B1/en active Active
- 2016-07-01 US US15/200,508 patent/US9464280B1/en active Active
- 2016-08-24 US US15/245,517 patent/US9695409B2/en active Active
-
2017
- 2017-06-02 US US15/611,881 patent/US9783797B1/en active Active
- 2017-08-10 US US15/674,177 patent/US10011824B2/en active Active
-
2018
- 2018-05-30 US US15/993,159 patent/US10087433B1/en active Active
- 2018-08-24 US US16/112,283 patent/US10336995B2/en active Active
-
2019
- 2019-05-16 US US16/414,411 patent/US10584326B2/en active Active
- 2019-12-05 JP JP2019220462A patent/JP7038094B2/ja active Active
-
2020
- 2020-01-24 US US16/751,734 patent/US10767171B2/en active Active
- 2020-07-24 US US16/938,318 patent/US11236319B2/en active Active
-
2021
- 2021-12-08 US US17/545,050 patent/US11608494B2/en active Active
-
2023
- 2023-02-07 US US18/165,470 patent/US20230313166A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013529905A (ja) * | 2010-05-24 | 2013-07-25 | プレヴァブ アール エルエルシー | 改変型β−ラクタマーゼ並びにそれに関する方法及び使用 |
Non-Patent Citations (4)
Title |
---|
ANTIMICROB. AGENTS CHEMOTHER., 2011, VOL. 55, NO. 1, PP. 284-290, JPN6019006736, ISSN: 0003986112 * |
ANTIMICROB. AGENTS CHEMOTHERM., 1995, VOL. 39, NO. 12, PP. 2593-2601, JPN6019006744, ISSN: 0003986115 * |
BIOCHIM. BIOPHYS. ACTA, 1999, VOL. 1433, PP. 153-158, JPN6019006737, ISSN: 0003986113 * |
PROTEINS: STRUC., FUNCT., GENET., 1989, VOL. 6, PP. 275-283, JPN6019006740, ISSN: 0003986114 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11608494B2 (en) | Beta-lactamases with improved properties for therapy | |
Amyes et al. | Antibiotic resistance in bacteria: —a review based on a symposium held on 5 January 1991 at Addenbrookes Hospital, Cambridge and chaired by Professor JT Smith | |
CN107530406B (zh) | 用于保护肠微生物群系的与抗生素一起使用的碳青霉烯酶 | |
US20120219952A1 (en) | Carbapenemase and antibacterial treatment | |
CN106574273B (zh) | β-内酰胺酶的基于大肠杆菌的生产 | |
Neuhaus | Strategies in B-lactam Design Francis C. Neuhaus and Nafsika Georgopapadakou |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180411 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180411 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190222 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190305 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190605 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20190806 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191205 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20200130 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200303 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200401 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6685925 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |