CN112646019B - 突变胞溶素孔 - Google Patents
突变胞溶素孔 Download PDFInfo
- Publication number
- CN112646019B CN112646019B CN202011579254.5A CN202011579254A CN112646019B CN 112646019 B CN112646019 B CN 112646019B CN 202011579254 A CN202011579254 A CN 202011579254A CN 112646019 B CN112646019 B CN 112646019B
- Authority
- CN
- China
- Prior art keywords
- leu
- glu
- ala
- gly
- val
- 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.)
- Active
Links
- 101710174798 Lysenin Proteins 0.000 title claims abstract description 84
- 239000011148 porous material Substances 0.000 title claims description 283
- 102000040430 polynucleotide Human genes 0.000 claims description 283
- 108091033319 polynucleotide Proteins 0.000 claims description 283
- 239000002157 polynucleotide Substances 0.000 claims description 283
- 239000000178 monomer Substances 0.000 claims description 265
- 238000000034 method Methods 0.000 claims description 129
- 102200075749 rs397514044 Human genes 0.000 claims description 115
- 102220076678 rs146651027 Human genes 0.000 claims description 108
- 102200101908 rs72554358 Human genes 0.000 claims description 103
- 238000006467 substitution reaction Methods 0.000 claims description 52
- 239000012491 analyte Substances 0.000 claims description 46
- 102000014914 Carrier Proteins Human genes 0.000 claims description 27
- 108091008324 binding proteins Proteins 0.000 claims description 26
- 238000005259 measurement Methods 0.000 claims description 25
- 238000010276 construction Methods 0.000 claims description 9
- 102220539335 Prostaglandin D2 receptor 2_E71S_mutation Human genes 0.000 claims description 8
- 102220530307 Calcium-transporting ATPase type 2C member 1_E50S_mutation Human genes 0.000 claims description 7
- 102220591546 Cysteine-rich hydrophobic domain-containing protein 1_E76S_mutation Human genes 0.000 claims description 3
- 102220493937 26S proteasome complex subunit SEM1_E167A_mutation Human genes 0.000 claims description 2
- 102220483642 Nuclear distribution protein nudE homolog 1_E84Q_mutation Human genes 0.000 claims 3
- 102220520572 Osteoclast-stimulating factor 1_N48S_mutation Human genes 0.000 claims 1
- 102200070587 rs763615602 Human genes 0.000 claims 1
- 102220072337 rs794728990 Human genes 0.000 claims 1
- 238000012512 characterization method Methods 0.000 abstract description 10
- 102000053602 DNA Human genes 0.000 description 209
- 108020004414 DNA Proteins 0.000 description 209
- 239000002773 nucleotide Substances 0.000 description 169
- 125000003729 nucleotide group Chemical group 0.000 description 167
- 235000001014 amino acid Nutrition 0.000 description 139
- 229940024606 amino acid Drugs 0.000 description 137
- 150000001413 amino acids Chemical class 0.000 description 123
- 230000035772 mutation Effects 0.000 description 73
- 102000004190 Enzymes Human genes 0.000 description 64
- 108090000790 Enzymes Proteins 0.000 description 64
- 108060004795 Methyltransferase Proteins 0.000 description 62
- 230000004048 modification Effects 0.000 description 62
- 238000012986 modification Methods 0.000 description 62
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 56
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 55
- 108090000623 proteins and genes Proteins 0.000 description 54
- 229910052700 potassium Inorganic materials 0.000 description 42
- 102000004169 proteins and genes Human genes 0.000 description 42
- 239000012528 membrane Substances 0.000 description 41
- 235000018102 proteins Nutrition 0.000 description 41
- 230000033001 locomotion Effects 0.000 description 40
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 39
- 108091023037 Aptamer Proteins 0.000 description 38
- 125000003275 alpha amino acid group Chemical group 0.000 description 38
- 239000011591 potassium Substances 0.000 description 38
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 37
- 229910052739 hydrogen Inorganic materials 0.000 description 37
- 235000004400 serine Nutrition 0.000 description 37
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 36
- -1 potassium ferricyanide Chemical compound 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 32
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 31
- 108060002716 Exonuclease Proteins 0.000 description 30
- 102000013165 exonuclease Human genes 0.000 description 30
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 30
- 101710126949 Lysin Proteins 0.000 description 28
- 230000003993 interaction Effects 0.000 description 28
- 238000012163 sequencing technique Methods 0.000 description 28
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 27
- 239000000872 buffer Substances 0.000 description 27
- 239000001103 potassium chloride Substances 0.000 description 27
- 235000011164 potassium chloride Nutrition 0.000 description 27
- 239000000523 sample Substances 0.000 description 27
- 239000000232 Lipid Bilayer Substances 0.000 description 24
- 230000008859 change Effects 0.000 description 24
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 23
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 23
- 230000001965 increasing effect Effects 0.000 description 22
- 150000007523 nucleic acids Chemical class 0.000 description 21
- 239000000758 substrate Substances 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 19
- 102000004196 processed proteins & peptides Human genes 0.000 description 19
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 18
- 235000009582 asparagine Nutrition 0.000 description 18
- 229960001230 asparagine Drugs 0.000 description 18
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 18
- 241000588724 Escherichia coli Species 0.000 description 17
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 17
- 238000007792 addition Methods 0.000 description 16
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical compound [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- 239000013615 primer Substances 0.000 description 14
- 102100022536 Helicase POLQ-like Human genes 0.000 description 13
- 101000899334 Homo sapiens Helicase POLQ-like Proteins 0.000 description 13
- 230000001976 improved effect Effects 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 12
- 235000018417 cysteine Nutrition 0.000 description 12
- 150000002632 lipids Chemical class 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 229920000858 Cyclodextrin Polymers 0.000 description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- 108020004682 Single-Stranded DNA Proteins 0.000 description 10
- 125000003636 chemical group Chemical group 0.000 description 10
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 10
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 10
- LTFMZDNNPPEQNG-KVQBGUIXSA-N 2'-deoxyguanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 LTFMZDNNPPEQNG-KVQBGUIXSA-N 0.000 description 9
- 239000004971 Cross linker Substances 0.000 description 9
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 9
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 9
- 241000880493 Leptailurus serval Species 0.000 description 9
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 9
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 9
- 235000013928 guanylic acid Nutrition 0.000 description 9
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 9
- 229930182817 methionine Natural products 0.000 description 9
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 9
- 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 8
- KHWCHTKSEGGWEX-RRKCRQDMSA-N 2'-deoxyadenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KHWCHTKSEGGWEX-RRKCRQDMSA-N 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 description 8
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 229920002477 rna polymer Polymers 0.000 description 8
- 102220070934 rs794728586 Human genes 0.000 description 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
- 241000243686 Eisenia fetida Species 0.000 description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
- 241000589499 Thermus thermophilus Species 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229920001400 block copolymer Polymers 0.000 description 7
- 235000012000 cholesterol Nutrition 0.000 description 7
- JSRLJPSBLDHEIO-SHYZEUOFSA-N dUMP Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 JSRLJPSBLDHEIO-SHYZEUOFSA-N 0.000 description 7
- 238000005755 formation reaction Methods 0.000 description 7
- 108010078144 glutaminyl-glycine Proteins 0.000 description 7
- 108010087823 glycyltyrosine Proteins 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 6
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 6
- 241000701959 Escherichia virus Lambda Species 0.000 description 6
- 108010006464 Hemolysin Proteins Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 6
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 6
- 108010038633 aspartylglutamate Proteins 0.000 description 6
- 108010092854 aspartyllysine Proteins 0.000 description 6
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 6
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 108010089804 glycyl-threonine Proteins 0.000 description 6
- 239000003228 hemolysin Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 108010034529 leucyl-lysine Proteins 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 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 5
- 102220634571 AP-2 complex subunit alpha-1_E92V_mutation Human genes 0.000 description 5
- 108091006112 ATPases Proteins 0.000 description 5
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 5
- 150000008574 D-amino acids Chemical class 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 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 description 5
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- CIKGWCTVFSRMJU-KVQBGUIXSA-N dGDP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 CIKGWCTVFSRMJU-KVQBGUIXSA-N 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000005684 electric field Effects 0.000 description 5
- 230000007831 electrophysiology Effects 0.000 description 5
- 238000002001 electrophysiology Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 5
- 108010049041 glutamylalanine Proteins 0.000 description 5
- 235000018977 lysine Nutrition 0.000 description 5
- 108010064235 lysylglycine Proteins 0.000 description 5
- 108010038320 lysylphenylalanine Proteins 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 229960005190 phenylalanine Drugs 0.000 description 5
- 239000000276 potassium ferrocyanide Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 102200142966 rs398124651 Human genes 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 4
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 4
- VBFJESQBIWCWRL-DCAQKATOSA-N Arg-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCNC(N)=N VBFJESQBIWCWRL-DCAQKATOSA-N 0.000 description 4
- ZUNMTUPRQMWMHX-LSJOCFKGSA-N Asp-Val-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O ZUNMTUPRQMWMHX-LSJOCFKGSA-N 0.000 description 4
- ZWIADYZPOWUWEW-XVFCMESISA-N CDP Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-XVFCMESISA-N 0.000 description 4
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 4
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 4
- QGWNDRXFNXRZMB-UUOKFMHZSA-N GDP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-N 0.000 description 4
- FLLRAEJOLZPSMN-CIUDSAMLSA-N Glu-Asn-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FLLRAEJOLZPSMN-CIUDSAMLSA-N 0.000 description 4
- QCMVGXDELYMZET-GLLZPBPUSA-N Glu-Thr-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QCMVGXDELYMZET-GLLZPBPUSA-N 0.000 description 4
- DTLLNDVORUEOTM-WDCWCFNPSA-N Glu-Thr-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DTLLNDVORUEOTM-WDCWCFNPSA-N 0.000 description 4
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 4
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 4
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- HVJVUYQWFYMGJS-GVXVVHGQSA-N Leu-Glu-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVJVUYQWFYMGJS-GVXVVHGQSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 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 4
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 102220640643 Polyadenylate-binding protein 1_E84S_mutation Human genes 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- RZCIEJXAILMSQK-JXOAFFINSA-N TTP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 RZCIEJXAILMSQK-JXOAFFINSA-N 0.000 description 4
- RFKVQLIXNVEOMB-WEDXCCLWSA-N Thr-Leu-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N)O RFKVQLIXNVEOMB-WEDXCCLWSA-N 0.000 description 4
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 102220505382 Uncharacterized protein C1orf141_E85G_mutation Human genes 0.000 description 4
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 4
- BZDVTEPMYMHZCR-JGVFFNPUSA-N [(2s,5r)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)CC1 BZDVTEPMYMHZCR-JGVFFNPUSA-N 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 108010008355 arginyl-glutamine Proteins 0.000 description 4
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 4
- 108010068380 arginylarginine Proteins 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- 108010093581 aspartyl-proline Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- FTDHDKPUHBLBTL-SHYZEUOFSA-K dCDP(3-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 FTDHDKPUHBLBTL-SHYZEUOFSA-K 0.000 description 4
- RGWHQCVHVJXOKC-SHYZEUOFSA-N dCTP Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-N 0.000 description 4
- UJLXYODCHAELLY-XLPZGREQSA-N dTDP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 UJLXYODCHAELLY-XLPZGREQSA-N 0.000 description 4
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 4
- QHWZTVCCBMIIKE-SHYZEUOFSA-N dUDP Chemical compound O1[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 QHWZTVCCBMIIKE-SHYZEUOFSA-N 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 4
- 108010050848 glycylleucine Proteins 0.000 description 4
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 4
- 108010040030 histidinoalanine Proteins 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 238000006384 oligomerization reaction Methods 0.000 description 4
- 108010051242 phenylalanylserine Proteins 0.000 description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 102220058338 rs730881989 Human genes 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 150000003573 thiols Chemical group 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 208000035657 Abasia Diseases 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- IKKVASZHTMKJIR-ZKWXMUAHSA-N Ala-Asp-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O IKKVASZHTMKJIR-ZKWXMUAHSA-N 0.000 description 3
- SSQHYGLFYWZWDV-UVBJJODRSA-N Ala-Val-Trp Chemical compound CC(C)[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O SSQHYGLFYWZWDV-UVBJJODRSA-N 0.000 description 3
- 102220483802 Aminopeptidase RNPEPL1_E84G_mutation Human genes 0.000 description 3
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 3
- LKDHUGLXOHYINY-XUXIUFHCSA-N Arg-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N LKDHUGLXOHYINY-XUXIUFHCSA-N 0.000 description 3
- UGIBTKGQVWFTGX-BIIVOSGPSA-N Asp-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O UGIBTKGQVWFTGX-BIIVOSGPSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 3
- BLGNLNRBABWDST-CIUDSAMLSA-N Cys-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BLGNLNRBABWDST-CIUDSAMLSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 108010007577 Exodeoxyribonuclease I Proteins 0.000 description 3
- 102100029075 Exonuclease 1 Human genes 0.000 description 3
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 3
- GWCJMBNBFYBQCV-XPUUQOCRSA-N Gly-Val-Ala Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O GWCJMBNBFYBQCV-XPUUQOCRSA-N 0.000 description 3
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 3
- OEROYDLRVAYIMQ-YUMQZZPRSA-N His-Gly-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O OEROYDLRVAYIMQ-YUMQZZPRSA-N 0.000 description 3
- JRHFQUPIZOYKQP-KBIXCLLPSA-N Ile-Ala-Glu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O JRHFQUPIZOYKQP-KBIXCLLPSA-N 0.000 description 3
- IDAHFEPYTJJZFD-PEFMBERDSA-N Ile-Asp-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N IDAHFEPYTJJZFD-PEFMBERDSA-N 0.000 description 3
- IXEFKXAGHRQFAF-HVTMNAMFSA-N Ile-Glu-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N IXEFKXAGHRQFAF-HVTMNAMFSA-N 0.000 description 3
- JXMSHKFPDIUYGS-SIUGBPQLSA-N Ile-Glu-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N JXMSHKFPDIUYGS-SIUGBPQLSA-N 0.000 description 3
- DSDPLOODKXISDT-XUXIUFHCSA-N Ile-Leu-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O DSDPLOODKXISDT-XUXIUFHCSA-N 0.000 description 3
- FQYQMFCIJNWDQZ-CYDGBPFRSA-N Ile-Pro-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 FQYQMFCIJNWDQZ-CYDGBPFRSA-N 0.000 description 3
- QHUREMVLLMNUAX-OSUNSFLBSA-N Ile-Thr-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)O)N QHUREMVLLMNUAX-OSUNSFLBSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- CQQGCWPXDHTTNF-GUBZILKMSA-N Leu-Ala-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O CQQGCWPXDHTTNF-GUBZILKMSA-N 0.000 description 3
- OGCQGUIWMSBHRZ-CIUDSAMLSA-N Leu-Asn-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OGCQGUIWMSBHRZ-CIUDSAMLSA-N 0.000 description 3
- PJWOOBTYQNNRBF-BZSNNMDCSA-N Leu-Phe-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)O)N PJWOOBTYQNNRBF-BZSNNMDCSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- WTZUSCUIVPVCRH-SRVKXCTJSA-N Lys-Gln-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WTZUSCUIVPVCRH-SRVKXCTJSA-N 0.000 description 3
- KZJQUYFDSCFSCO-DLOVCJGASA-N Lys-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCCN)N KZJQUYFDSCFSCO-DLOVCJGASA-N 0.000 description 3
- NCZIQZYZPUPMKY-PPCPHDFISA-N Lys-Ile-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NCZIQZYZPUPMKY-PPCPHDFISA-N 0.000 description 3
- ZJSXCIMWLPSTMG-HSCHXYMDSA-N Lys-Trp-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZJSXCIMWLPSTMG-HSCHXYMDSA-N 0.000 description 3
- FZDOBWIKRQORAC-ULQDDVLXSA-N Met-Tyr-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCSC)N FZDOBWIKRQORAC-ULQDDVLXSA-N 0.000 description 3
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- JTKGCYOOJLUETJ-ULQDDVLXSA-N Phe-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 JTKGCYOOJLUETJ-ULQDDVLXSA-N 0.000 description 3
- HFZNNDWPHBRNPV-KZVJFYERSA-N Pro-Ala-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HFZNNDWPHBRNPV-KZVJFYERSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- PPCZVWHJWJFTFN-ZLUOBGJFSA-N Ser-Ser-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O PPCZVWHJWJFTFN-ZLUOBGJFSA-N 0.000 description 3
- PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- VOGXLRKCWFLJBY-HSHDSVGOSA-N Thr-Arg-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VOGXLRKCWFLJBY-HSHDSVGOSA-N 0.000 description 3
- IMDMLDSVUSMAEJ-HJGDQZAQSA-N Thr-Leu-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IMDMLDSVUSMAEJ-HJGDQZAQSA-N 0.000 description 3
- FDQXPJCLVPFKJW-KJEVXHAQSA-N Thr-Met-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N)O FDQXPJCLVPFKJW-KJEVXHAQSA-N 0.000 description 3
- KZTLZZQTJMCGIP-ZJDVBMNYSA-N Thr-Val-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KZTLZZQTJMCGIP-ZJDVBMNYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- XGFOXYJQBRTJPO-PJODQICGSA-N Trp-Pro-Ala Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XGFOXYJQBRTJPO-PJODQICGSA-N 0.000 description 3
- AVFGBGGRZOKSFS-KJEVXHAQSA-N Tyr-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O AVFGBGGRZOKSFS-KJEVXHAQSA-N 0.000 description 3
- LMKKMCGTDANZTR-BZSNNMDCSA-N Tyr-Phe-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=C(O)C=C1 LMKKMCGTDANZTR-BZSNNMDCSA-N 0.000 description 3
- YKBUNNNRNZZUID-UFYCRDLUSA-N Tyr-Val-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YKBUNNNRNZZUID-UFYCRDLUSA-N 0.000 description 3
- ZLFHAAGHGQBQQN-GUBZILKMSA-N Val-Ala-Pro Natural products CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O ZLFHAAGHGQBQQN-GUBZILKMSA-N 0.000 description 3
- VLDMQVZZWDOKQF-AUTRQRHGSA-N Val-Glu-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VLDMQVZZWDOKQF-AUTRQRHGSA-N 0.000 description 3
- DLLRRUDLMSJTMB-GUBZILKMSA-N Val-Ser-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)O)N DLLRRUDLMSJTMB-GUBZILKMSA-N 0.000 description 3
- JVGDAEKKZKKZFO-RCWTZXSCSA-N Val-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N)O JVGDAEKKZKKZFO-RCWTZXSCSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 3
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 108010013835 arginine glutamate Proteins 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 3
- 108010047857 aspartylglycine Proteins 0.000 description 3
- 108010068265 aspartyltyrosine Proteins 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- DAEAPNUQQAICNR-RRKCRQDMSA-K dADP(3-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP([O-])(=O)OP([O-])([O-])=O)O1 DAEAPNUQQAICNR-RRKCRQDMSA-K 0.000 description 3
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 108010052305 exodeoxyribonuclease III Proteins 0.000 description 3
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 3
- 108010025306 histidylleucine Proteins 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 108010012581 phenylalanylglutamate Proteins 0.000 description 3
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 3
- 108010029020 prolylglycine Proteins 0.000 description 3
- 108010015796 prolylisoleucine Proteins 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 3
- 108010071207 serylmethionine Proteins 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- BYGOPQKDHGXNCD-UHFFFAOYSA-N tripotassium;iron(3+);hexacyanide Chemical compound [K+].[K+].[K+].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] BYGOPQKDHGXNCD-UHFFFAOYSA-N 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 108010020532 tyrosyl-proline Proteins 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- AUTOLBMXDDTRRT-JGVFFNPUSA-N (4R,5S)-dethiobiotin Chemical compound C[C@@H]1NC(=O)N[C@@H]1CCCCCC(O)=O AUTOLBMXDDTRRT-JGVFFNPUSA-N 0.000 description 2
- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 description 2
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 2
- GWFSQQNGMPGBEF-GHCJXIJMSA-N Ala-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N GWFSQQNGMPGBEF-GHCJXIJMSA-N 0.000 description 2
- BLGHHPHXVJWCNK-GUBZILKMSA-N Ala-Gln-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BLGHHPHXVJWCNK-GUBZILKMSA-N 0.000 description 2
- LNNSWWRRYJLGNI-NAKRPEOUSA-N Ala-Ile-Val Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O LNNSWWRRYJLGNI-NAKRPEOUSA-N 0.000 description 2
- OINVDEKBKBCPLX-JXUBOQSCSA-N Ala-Lys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OINVDEKBKBCPLX-JXUBOQSCSA-N 0.000 description 2
- AAWLEICNDUHIJM-MBLNEYKQSA-N Ala-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C)N)O AAWLEICNDUHIJM-MBLNEYKQSA-N 0.000 description 2
- UBTKNYUAMYRMKE-GOPGUHFVSA-N Ala-Trp-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N UBTKNYUAMYRMKE-GOPGUHFVSA-N 0.000 description 2
- TVUFMYKTYXTRPY-HERUPUMHSA-N Ala-Trp-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O TVUFMYKTYXTRPY-HERUPUMHSA-N 0.000 description 2
- KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 2
- JCAISGGAOQXEHJ-ZPFDUUQYSA-N Arg-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N JCAISGGAOQXEHJ-ZPFDUUQYSA-N 0.000 description 2
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-N 0.000 description 2
- NPAVRDPEFVKELR-DCAQKATOSA-N Arg-Lys-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O NPAVRDPEFVKELR-DCAQKATOSA-N 0.000 description 2
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 2
- YHZQOSXDTFRZKU-WDSOQIARSA-N Arg-Trp-Leu Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N)=CNC2=C1 YHZQOSXDTFRZKU-WDSOQIARSA-N 0.000 description 2
- COWITDLVHMZSIW-CIUDSAMLSA-N Asn-Lys-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O COWITDLVHMZSIW-CIUDSAMLSA-N 0.000 description 2
- REQUGIWGOGSOEZ-ZLUOBGJFSA-N Asn-Ser-Asn Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)C(=O)N REQUGIWGOGSOEZ-ZLUOBGJFSA-N 0.000 description 2
- HBUJSDCLZCXXCW-YDHLFZDLSA-N Asn-Val-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HBUJSDCLZCXXCW-YDHLFZDLSA-N 0.000 description 2
- FANQWNCPNFEPGZ-WHFBIAKZSA-N Asp-Asp-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O FANQWNCPNFEPGZ-WHFBIAKZSA-N 0.000 description 2
- VZNOVQKGJQJOCS-SRVKXCTJSA-N Asp-Asp-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VZNOVQKGJQJOCS-SRVKXCTJSA-N 0.000 description 2
- OVPHVTCDVYYTHN-AVGNSLFASA-N Asp-Glu-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OVPHVTCDVYYTHN-AVGNSLFASA-N 0.000 description 2
- QCVXMEHGFUMKCO-YUMQZZPRSA-N Asp-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O QCVXMEHGFUMKCO-YUMQZZPRSA-N 0.000 description 2
- ZXRQJQCXPSMNMR-XIRDDKMYSA-N Asp-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N ZXRQJQCXPSMNMR-XIRDDKMYSA-N 0.000 description 2
- GGRSYTUJHAZTFN-IHRRRGAJSA-N Asp-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O GGRSYTUJHAZTFN-IHRRRGAJSA-N 0.000 description 2
- QSFHZPQUAAQHAQ-CIUDSAMLSA-N Asp-Ser-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O QSFHZPQUAAQHAQ-CIUDSAMLSA-N 0.000 description 2
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-N 0.000 description 2
- KNDCWFXCFKSEBM-AVGNSLFASA-N Asp-Tyr-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O KNDCWFXCFKSEBM-AVGNSLFASA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000193388 Bacillus thuringiensis Species 0.000 description 2
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 2
- 229930195711 D-Serine Natural products 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- REJJNXODKSHOKA-ACZMJKKPSA-N Gln-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N REJJNXODKSHOKA-ACZMJKKPSA-N 0.000 description 2
- CELXWPDNIGWCJN-WDCWCFNPSA-N Gln-Lys-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CELXWPDNIGWCJN-WDCWCFNPSA-N 0.000 description 2
- VGUYMZGLJUJRBV-YVNDNENWSA-N Glu-Ile-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O VGUYMZGLJUJRBV-YVNDNENWSA-N 0.000 description 2
- ITBHUUMCJJQUSC-LAEOZQHASA-N Glu-Ile-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O ITBHUUMCJJQUSC-LAEOZQHASA-N 0.000 description 2
- DAHLWSFUXOHMIA-FXQIFTODSA-N Glu-Ser-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O DAHLWSFUXOHMIA-FXQIFTODSA-N 0.000 description 2
- VNCNWQPIQYAMAK-ACZMJKKPSA-N Glu-Ser-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O VNCNWQPIQYAMAK-ACZMJKKPSA-N 0.000 description 2
- HJTSRYLPAYGEEC-SIUGBPQLSA-N Glu-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)O)N HJTSRYLPAYGEEC-SIUGBPQLSA-N 0.000 description 2
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 2
- SOEATRRYCIPEHA-BQBZGAKWSA-N Gly-Glu-Glu Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SOEATRRYCIPEHA-BQBZGAKWSA-N 0.000 description 2
- QSVCIFZPGLOZGH-WDSKDSINSA-N Gly-Glu-Ser Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QSVCIFZPGLOZGH-WDSKDSINSA-N 0.000 description 2
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 2
- KAJAOGBVWCYGHZ-JTQLQIEISA-N Gly-Gly-Phe Chemical compound [NH3+]CC(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KAJAOGBVWCYGHZ-JTQLQIEISA-N 0.000 description 2
- UQJNXZSSGQIPIQ-FBCQKBJTSA-N Gly-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)CN UQJNXZSSGQIPIQ-FBCQKBJTSA-N 0.000 description 2
- DGKBSGNCMCLDSL-BYULHYEWSA-N Gly-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN DGKBSGNCMCLDSL-BYULHYEWSA-N 0.000 description 2
- SCWYHUQOOFRVHP-MBLNEYKQSA-N Gly-Ile-Thr Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SCWYHUQOOFRVHP-MBLNEYKQSA-N 0.000 description 2
- ZWRDOVYMQAAISL-UWVGGRQHSA-N Gly-Met-Lys Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCCN ZWRDOVYMQAAISL-UWVGGRQHSA-N 0.000 description 2
- FXLVSYVJDPCIHH-STQMWFEESA-N Gly-Phe-Arg Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FXLVSYVJDPCIHH-STQMWFEESA-N 0.000 description 2
- VDCRBJACQKOSMS-JSGCOSHPSA-N Gly-Phe-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O VDCRBJACQKOSMS-JSGCOSHPSA-N 0.000 description 2
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 2
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 108091093094 Glycol nucleic acid Proteins 0.000 description 2
- AIPUZFXMXAHZKY-QWRGUYRKSA-N His-Leu-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AIPUZFXMXAHZKY-QWRGUYRKSA-N 0.000 description 2
- ATXGFMOBVKSOMK-PEDHHIEDSA-N Ile-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N ATXGFMOBVKSOMK-PEDHHIEDSA-N 0.000 description 2
- NULSANWBUWLTKN-NAKRPEOUSA-N Ile-Arg-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N NULSANWBUWLTKN-NAKRPEOUSA-N 0.000 description 2
- PXKACEXYLPBMAD-JBDRJPRFSA-N Ile-Ser-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PXKACEXYLPBMAD-JBDRJPRFSA-N 0.000 description 2
- CNMOKANDJMLAIF-CIQUZCHMSA-N Ile-Thr-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O CNMOKANDJMLAIF-CIQUZCHMSA-N 0.000 description 2
- NURNJECQNNCRBK-FLBSBUHZSA-N Ile-Thr-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NURNJECQNNCRBK-FLBSBUHZSA-N 0.000 description 2
- ZYVTXBXHIKGZMD-QSFUFRPTSA-N Ile-Val-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ZYVTXBXHIKGZMD-QSFUFRPTSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 2
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 2
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 2
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 2
- PIHFVNPEAHFNLN-KKUMJFAQSA-N Leu-Cys-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N PIHFVNPEAHFNLN-KKUMJFAQSA-N 0.000 description 2
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 2
- AIRUUHAOKGVJAD-JYJNAYRXSA-N Leu-Phe-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIRUUHAOKGVJAD-JYJNAYRXSA-N 0.000 description 2
- DRWMRVFCKKXHCH-BZSNNMDCSA-N Leu-Phe-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CC=CC=C1 DRWMRVFCKKXHCH-BZSNNMDCSA-N 0.000 description 2
- KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 description 2
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 2
- PBLLTSKBTAHDNA-KBPBESRZSA-N Lys-Gly-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PBLLTSKBTAHDNA-KBPBESRZSA-N 0.000 description 2
- SLQJJFAVWSZLBL-BJDJZHNGSA-N Lys-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN SLQJJFAVWSZLBL-BJDJZHNGSA-N 0.000 description 2
- NJNRBRKHOWSGMN-SRVKXCTJSA-N Lys-Leu-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O NJNRBRKHOWSGMN-SRVKXCTJSA-N 0.000 description 2
- XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 2
- ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 2
- RPWTZTBIFGENIA-VOAKCMCISA-N Lys-Thr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O RPWTZTBIFGENIA-VOAKCMCISA-N 0.000 description 2
- LMMBAXJRYSXCOQ-ACRUOGEOSA-N Lys-Tyr-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O LMMBAXJRYSXCOQ-ACRUOGEOSA-N 0.000 description 2
- VWPJQIHBBOJWDN-DCAQKATOSA-N Lys-Val-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O VWPJQIHBBOJWDN-DCAQKATOSA-N 0.000 description 2
- 102220528081 M1-specific T cell receptor alpha chain_H58S_mutation Human genes 0.000 description 2
- CIDICGYKRUTYLE-FXQIFTODSA-N Met-Ser-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O CIDICGYKRUTYLE-FXQIFTODSA-N 0.000 description 2
- MIXPUVSPPOWTCR-FXQIFTODSA-N Met-Ser-Ser Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MIXPUVSPPOWTCR-FXQIFTODSA-N 0.000 description 2
- IHRFZLQEQVHXFA-RHYQMDGZSA-N Met-Thr-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCCN IHRFZLQEQVHXFA-RHYQMDGZSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- OZBFLQITCMCIOY-FOUAGVGXSA-N OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO OZBFLQITCMCIOY-FOUAGVGXSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- MPFGIYLYWUCSJG-AVGNSLFASA-N Phe-Glu-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 MPFGIYLYWUCSJG-AVGNSLFASA-N 0.000 description 2
- DNAXXTQSTKOHFO-QEJZJMRPSA-N Phe-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 DNAXXTQSTKOHFO-QEJZJMRPSA-N 0.000 description 2
- WLYPRKLMRIYGPP-JYJNAYRXSA-N Phe-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 WLYPRKLMRIYGPP-JYJNAYRXSA-N 0.000 description 2
- YOFKMVUAZGPFCF-IHRRRGAJSA-N Phe-Met-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(O)=O YOFKMVUAZGPFCF-IHRRRGAJSA-N 0.000 description 2
- JLLJTMHNXQTMCK-UBHSHLNASA-N Phe-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 JLLJTMHNXQTMCK-UBHSHLNASA-N 0.000 description 2
- LTAWNJXSRUCFAN-UNQGMJICSA-N Phe-Thr-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LTAWNJXSRUCFAN-UNQGMJICSA-N 0.000 description 2
- GNRMAQSIROFNMI-IXOXFDKPSA-N Phe-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GNRMAQSIROFNMI-IXOXFDKPSA-N 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 101000606032 Pomacea maculata Perivitellin-2 31 kDa subunit Proteins 0.000 description 2
- 101000606027 Pomacea maculata Perivitellin-2 67 kDa subunit Proteins 0.000 description 2
- UAYHMOIGIQZLFR-NHCYSSNCSA-N Pro-Gln-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O UAYHMOIGIQZLFR-NHCYSSNCSA-N 0.000 description 2
- VPEVBAUSTBWQHN-NHCYSSNCSA-N Pro-Glu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O VPEVBAUSTBWQHN-NHCYSSNCSA-N 0.000 description 2
- QEWBZBLXDKIQPS-STQMWFEESA-N Pro-Gly-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QEWBZBLXDKIQPS-STQMWFEESA-N 0.000 description 2
- JIWJRKNYLSHONY-KKUMJFAQSA-N Pro-Phe-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O JIWJRKNYLSHONY-KKUMJFAQSA-N 0.000 description 2
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 2
- 108091093078 Pyrimidine dimer Proteins 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- BRKHVZNDAOMAHX-BIIVOSGPSA-N Ser-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N BRKHVZNDAOMAHX-BIIVOSGPSA-N 0.000 description 2
- GXXTUIUYTWGPMV-FXQIFTODSA-N Ser-Arg-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O GXXTUIUYTWGPMV-FXQIFTODSA-N 0.000 description 2
- QFBNNYNWKYKVJO-DCAQKATOSA-N Ser-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N QFBNNYNWKYKVJO-DCAQKATOSA-N 0.000 description 2
- HVKMTOIAYDOJPL-NRPADANISA-N Ser-Gln-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVKMTOIAYDOJPL-NRPADANISA-N 0.000 description 2
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 2
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 2
- ZFVFHHZBCVNLGD-GUBZILKMSA-N Ser-His-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFVFHHZBCVNLGD-GUBZILKMSA-N 0.000 description 2
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 2
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 2
- WGDYNRCOQRERLZ-KKUMJFAQSA-N Ser-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N WGDYNRCOQRERLZ-KKUMJFAQSA-N 0.000 description 2
- HAUVENOGHPECML-BPUTZDHNSA-N Ser-Trp-Val Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CO)=CNC2=C1 HAUVENOGHPECML-BPUTZDHNSA-N 0.000 description 2
- 102220503470 Superoxide dismutase [Cu-Zn]_H81S_mutation Human genes 0.000 description 2
- 108010076818 TEV protease Proteins 0.000 description 2
- OJRNZRROAIAHDL-LKXGYXEUSA-N Thr-Asn-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OJRNZRROAIAHDL-LKXGYXEUSA-N 0.000 description 2
- PZVGOVRNGKEFCB-KKHAAJSZSA-N Thr-Asn-Val Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N)O PZVGOVRNGKEFCB-KKHAAJSZSA-N 0.000 description 2
- KGKWKSSSQGGYAU-SUSMZKCASA-N Thr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KGKWKSSSQGGYAU-SUSMZKCASA-N 0.000 description 2
- XOTBWOCSLMBGMF-SUSMZKCASA-N Thr-Glu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOTBWOCSLMBGMF-SUSMZKCASA-N 0.000 description 2
- BNGDYRRHRGOPHX-IFFSRLJSSA-N Thr-Glu-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O BNGDYRRHRGOPHX-IFFSRLJSSA-N 0.000 description 2
- IMULJHHGAUZZFE-MBLNEYKQSA-N Thr-Gly-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IMULJHHGAUZZFE-MBLNEYKQSA-N 0.000 description 2
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-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
- ZMYCLHFLHRVOEA-HEIBUPTGSA-N Thr-Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ZMYCLHFLHRVOEA-HEIBUPTGSA-N 0.000 description 2
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 2
- AKHDFZHUPGVFEJ-YEPSODPASA-N Thr-Val-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AKHDFZHUPGVFEJ-YEPSODPASA-N 0.000 description 2
- 108091046915 Threose nucleic acid Proteins 0.000 description 2
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- NMCBVGFGWSIGSB-NUTKFTJISA-N Trp-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N NMCBVGFGWSIGSB-NUTKFTJISA-N 0.000 description 2
- NIWAGRRZHCMPOY-GMVOTWDCSA-N Trp-Ala-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N NIWAGRRZHCMPOY-GMVOTWDCSA-N 0.000 description 2
- 108010028230 Trp-Ser- His-Pro-Gln-Phe-Glu-Lys Proteins 0.000 description 2
- KSVMDJJCYKIXTK-IGNZVWTISA-N Tyr-Ala-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 KSVMDJJCYKIXTK-IGNZVWTISA-N 0.000 description 2
- JRXKIVGWMMIIOF-YDHLFZDLSA-N Tyr-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JRXKIVGWMMIIOF-YDHLFZDLSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- AUMNPAUHKUNHHN-BYULHYEWSA-N Val-Asn-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N AUMNPAUHKUNHHN-BYULHYEWSA-N 0.000 description 2
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 2
- UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 2
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 2
- YTUABZMPYKCWCQ-XQQFMLRXSA-N Val-His-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@@H]2C(=O)O)N YTUABZMPYKCWCQ-XQQFMLRXSA-N 0.000 description 2
- VXDSPJJQUQDCKH-UKJIMTQDSA-N Val-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N VXDSPJJQUQDCKH-UKJIMTQDSA-N 0.000 description 2
- UKEVLVBHRKWECS-LSJOCFKGSA-N Val-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](C(C)C)N UKEVLVBHRKWECS-LSJOCFKGSA-N 0.000 description 2
- CXWJFWAZIVWBOS-XQQFMLRXSA-N Val-Lys-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N CXWJFWAZIVWBOS-XQQFMLRXSA-N 0.000 description 2
- QZKVWWIUSQGWMY-IHRRRGAJSA-N Val-Ser-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QZKVWWIUSQGWMY-IHRRRGAJSA-N 0.000 description 2
- DVLWZWNAQUBZBC-ZNSHCXBVSA-N Val-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N)O DVLWZWNAQUBZBC-ZNSHCXBVSA-N 0.000 description 2
- IECQJCJNPJVUSB-IHRRRGAJSA-N Val-Tyr-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(O)=O IECQJCJNPJVUSB-IHRRRGAJSA-N 0.000 description 2
- 238000005411 Van der Waals force Methods 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- PGAVKCOVUIYSFO-UHFFFAOYSA-N [[5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 108010005233 alanylglutamic acid Proteins 0.000 description 2
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 229940097012 bacillus thuringiensis Drugs 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000002800 charge carrier Substances 0.000 description 2
- 150000003841 chloride salts Chemical class 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- FPUGCISOLXNPPC-IOSLPCCCSA-N cordysinin B Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-IOSLPCCCSA-N 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 230000006862 enzymatic digestion Effects 0.000 description 2
- 125000001924 fatty-acyl group Chemical group 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 2
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 2
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 2
- 108010015792 glycyllysine Proteins 0.000 description 2
- 108010077515 glycylproline Proteins 0.000 description 2
- 229910021389 graphene Inorganic materials 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 108010036413 histidylglycine Proteins 0.000 description 2
- 108010092114 histidylphenylalanine Proteins 0.000 description 2
- 108010085325 histidylproline Proteins 0.000 description 2
- 108010018006 histidylserine Proteins 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 108010078274 isoleucylvaline Proteins 0.000 description 2
- 238000000111 isothermal titration calorimetry Methods 0.000 description 2
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 108010003700 lysyl aspartic acid Proteins 0.000 description 2
- 108010009298 lysylglutamic acid Proteins 0.000 description 2
- 108010017391 lysylvaline Proteins 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 108010022588 methionyl-lysyl-proline Proteins 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000004712 monophosphates Chemical class 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000001293 nucleolytic effect Effects 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 230000003606 oligomerizing effect Effects 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 108010090894 prolylleucine Proteins 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 239000013635 pyrimidine dimer Substances 0.000 description 2
- 101150056906 recJ gene Proteins 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 239000003237 recreational drug Substances 0.000 description 2
- 239000004180 red 2G Substances 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 108010005652 splenotritin Proteins 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 239000004149 tartrazine Substances 0.000 description 2
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 2
- 108010015666 tryptophyl-leucyl-glutamic acid Proteins 0.000 description 2
- 108010051110 tyrosyl-lysine Proteins 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 1
- IGXNPQWXIRIGBF-KEOOTSPTSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IGXNPQWXIRIGBF-KEOOTSPTSA-N 0.000 description 1
- NEMHIKRLROONTL-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-azidophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N=[N+]=[N-])C=C1 NEMHIKRLROONTL-QMMMGPOBSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- MUSPKJVFRAYWAR-XVFCMESISA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)thiolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)S[C@H]1N1C(=O)NC(=O)C=C1 MUSPKJVFRAYWAR-XVFCMESISA-N 0.000 description 1
- QPHRQMAYYMYWFW-FJGDRVTGSA-N 1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 QPHRQMAYYMYWFW-FJGDRVTGSA-N 0.000 description 1
- HRSBDXXXHGAUJF-QJPTWQEYSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-pent-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CCCC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 HRSBDXXXHGAUJF-QJPTWQEYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-ULQXZJNLSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidine-2,4-dione Chemical compound O=C1NC(=O)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 MXHRCPNRJAMMIM-ULQXZJNLSA-N 0.000 description 1
- BMQZYMYBQZGEEY-UHFFFAOYSA-M 1-ethyl-3-methylimidazolium chloride Chemical compound [Cl-].CCN1C=C[N+](C)=C1 BMQZYMYBQZGEEY-UHFFFAOYSA-M 0.000 description 1
- HWPZZUQOWRWFDB-UHFFFAOYSA-N 1-methylcytosine Chemical compound CN1C=CC(N)=NC1=O HWPZZUQOWRWFDB-UHFFFAOYSA-N 0.000 description 1
- FPUGCISOLXNPPC-UHFFFAOYSA-N 2'-O-Methyladenosine Natural products COC1C(O)C(CO)OC1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-UHFFFAOYSA-N 2'-O-Methylcytidine Natural products COC1C(O)C(CO)OC1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-UHFFFAOYSA-N 0.000 description 1
- OVYNGSFVYRPRCG-UHFFFAOYSA-N 2'-O-Methylguanosine Natural products COC1C(O)C(CO)OC1N1C(NC(N)=NC2=O)=C2N=C1 OVYNGSFVYRPRCG-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-ZOQUXTDFSA-N 2'-O-methylcytidine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-ZOQUXTDFSA-N 0.000 description 1
- OVYNGSFVYRPRCG-KQYNXXCUSA-N 2'-O-methylguanosine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=C(N)NC2=O)=C2N=C1 OVYNGSFVYRPRCG-KQYNXXCUSA-N 0.000 description 1
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 description 1
- RQKDPSTWKKMBPM-XLPZGREQSA-N 2'-deoxy-5-hydroxymethyl-CDP Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 RQKDPSTWKKMBPM-XLPZGREQSA-N 0.000 description 1
- DLHNIFPAUZVLLA-XLPZGREQSA-N 2'-deoxy-5-hydroxymethyl-CTP Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 DLHNIFPAUZVLLA-XLPZGREQSA-N 0.000 description 1
- RGDVNLHBCKWZDA-XLPZGREQSA-N 2'-deoxy-5-methyl-5'-cytidylic acid Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 RGDVNLHBCKWZDA-XLPZGREQSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical group Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical group SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
- LMZHZBVAKAMCEG-FJGDRVTGSA-N 4-amino-1-[(2r,3r,4r,5r)-3-amino-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@](O)(N)[C@H](O)[C@@H](CO)O1 LMZHZBVAKAMCEG-FJGDRVTGSA-N 0.000 description 1
- GAKJJSAXUFZQTL-XVFCMESISA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)thiolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)S1 GAKJJSAXUFZQTL-XVFCMESISA-N 0.000 description 1
- PJWBTAIPBFWVHX-FJGDRVTGSA-N 4-amino-1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@](F)(O)[C@H](O)[C@@H](CO)O1 PJWBTAIPBFWVHX-FJGDRVTGSA-N 0.000 description 1
- YAWQLNSJZSCVAG-TURQNECASA-N 5-(3-aminopropyl)-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(CCCN)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YAWQLNSJZSCVAG-TURQNECASA-N 0.000 description 1
- 108010036211 5-HT-moduline Proteins 0.000 description 1
- BTIWPBKNTZFNRI-XLPZGREQSA-N 5-hydroxymethyldeoxycytidylic acid Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 BTIWPBKNTZFNRI-XLPZGREQSA-N 0.000 description 1
- NGYHUCPPLJOZIX-XLPZGREQSA-N 5-methyl-dCTP Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NGYHUCPPLJOZIX-XLPZGREQSA-N 0.000 description 1
- NJQONZSFUKNYOY-JXOAFFINSA-N 5-methylcytidine 5'-monophosphate Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 NJQONZSFUKNYOY-JXOAFFINSA-N 0.000 description 1
- SHFOWZBOBJJZAP-XLPZGREQSA-N 5-methyldeoxycytidine 5'-(trihydrogen diphosphate) Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 SHFOWZBOBJJZAP-XLPZGREQSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 1
- FJVAQLJNTSUQPY-CIUDSAMLSA-N Ala-Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN FJVAQLJNTSUQPY-CIUDSAMLSA-N 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- SSSROGPPPVTHLX-FXQIFTODSA-N Ala-Arg-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSSROGPPPVTHLX-FXQIFTODSA-N 0.000 description 1
- SKHCUBQVZJHOFM-NAKRPEOUSA-N Ala-Arg-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SKHCUBQVZJHOFM-NAKRPEOUSA-N 0.000 description 1
- YWWATNIVMOCSAV-UBHSHLNASA-N Ala-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YWWATNIVMOCSAV-UBHSHLNASA-N 0.000 description 1
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 1
- JAMAWBXXKFGFGX-KZVJFYERSA-N Ala-Arg-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JAMAWBXXKFGFGX-KZVJFYERSA-N 0.000 description 1
- XCVRVWZTXPCYJT-BIIVOSGPSA-N Ala-Asn-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N XCVRVWZTXPCYJT-BIIVOSGPSA-N 0.000 description 1
- GORKKVHIBWAQHM-GCJQMDKQSA-N Ala-Asn-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GORKKVHIBWAQHM-GCJQMDKQSA-N 0.000 description 1
- XQJAFSDFQZPYCU-UWJYBYFXSA-N Ala-Asn-Tyr Chemical compound 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 XQJAFSDFQZPYCU-UWJYBYFXSA-N 0.000 description 1
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 1
- 108010040956 Ala-Asp-Glu-Leu Proteins 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- ZIWWTZWAKYBUOB-CIUDSAMLSA-N Ala-Asp-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O ZIWWTZWAKYBUOB-CIUDSAMLSA-N 0.000 description 1
- MKZCBYZBCINNJN-DLOVCJGASA-N Ala-Asp-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MKZCBYZBCINNJN-DLOVCJGASA-N 0.000 description 1
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 1
- LGFCAXJBAZESCF-ACZMJKKPSA-N Ala-Gln-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O LGFCAXJBAZESCF-ACZMJKKPSA-N 0.000 description 1
- CXQODNIBUNQWAS-CIUDSAMLSA-N Ala-Gln-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CXQODNIBUNQWAS-CIUDSAMLSA-N 0.000 description 1
- NKJBKNVQHBZUIX-ACZMJKKPSA-N Ala-Gln-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKJBKNVQHBZUIX-ACZMJKKPSA-N 0.000 description 1
- JPGBXANAQYHTLA-DRZSPHRISA-N Ala-Gln-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JPGBXANAQYHTLA-DRZSPHRISA-N 0.000 description 1
- ZDYNWWQXFRUOEO-XDTLVQLUSA-N Ala-Gln-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDYNWWQXFRUOEO-XDTLVQLUSA-N 0.000 description 1
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 1
- NWVVKQZOVSTDBQ-CIUDSAMLSA-N Ala-Glu-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NWVVKQZOVSTDBQ-CIUDSAMLSA-N 0.000 description 1
- KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 1
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 1
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 1
- PCIFXPRIFWKWLK-YUMQZZPRSA-N Ala-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N PCIFXPRIFWKWLK-YUMQZZPRSA-N 0.000 description 1
- QHASENCZLDHBGX-ONGXEEELSA-N Ala-Gly-Phe Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QHASENCZLDHBGX-ONGXEEELSA-N 0.000 description 1
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 1
- GRPHQEMIFDPKOE-HGNGGELXSA-N Ala-His-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O GRPHQEMIFDPKOE-HGNGGELXSA-N 0.000 description 1
- CBCCCLMNOBLBSC-XVYDVKMFSA-N Ala-His-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O CBCCCLMNOBLBSC-XVYDVKMFSA-N 0.000 description 1
- NYDBKUNVSALYPX-NAKRPEOUSA-N Ala-Ile-Arg Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NYDBKUNVSALYPX-NAKRPEOUSA-N 0.000 description 1
- HHRAXZAYZFFRAM-CIUDSAMLSA-N Ala-Leu-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O HHRAXZAYZFFRAM-CIUDSAMLSA-N 0.000 description 1
- WUHJHHGYVVJMQE-BJDJZHNGSA-N Ala-Leu-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WUHJHHGYVVJMQE-BJDJZHNGSA-N 0.000 description 1
- QPBSRMDNJOTFAL-AICCOOGYSA-N Ala-Leu-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QPBSRMDNJOTFAL-AICCOOGYSA-N 0.000 description 1
- FCXAUASCMJOFEY-NDKCEZKHSA-N Ala-Leu-Thr-Pro 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)N1CCC[C@H]1C(O)=O FCXAUASCMJOFEY-NDKCEZKHSA-N 0.000 description 1
- CHFFHQUVXHEGBY-GARJFASQSA-N Ala-Lys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N CHFFHQUVXHEGBY-GARJFASQSA-N 0.000 description 1
- DRARURMRLANNLS-GUBZILKMSA-N Ala-Met-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(O)=O DRARURMRLANNLS-GUBZILKMSA-N 0.000 description 1
- 108010011667 Ala-Phe-Ala Proteins 0.000 description 1
- RUXQNKVQSKOOBS-JURCDPSOSA-N Ala-Phe-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RUXQNKVQSKOOBS-JURCDPSOSA-N 0.000 description 1
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 1
- YHBDGLZYNIARKJ-GUBZILKMSA-N Ala-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N YHBDGLZYNIARKJ-GUBZILKMSA-N 0.000 description 1
- RMAWDDRDTRSZIR-ZLUOBGJFSA-N Ala-Ser-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RMAWDDRDTRSZIR-ZLUOBGJFSA-N 0.000 description 1
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 1
- NHWYNIZWLJYZAG-XVYDVKMFSA-N Ala-Ser-His Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N NHWYNIZWLJYZAG-XVYDVKMFSA-N 0.000 description 1
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 1
- KTXKIYXZQFWJKB-VZFHVOOUSA-N Ala-Thr-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O KTXKIYXZQFWJKB-VZFHVOOUSA-N 0.000 description 1
- XPBVBZPVNFIHOA-UVBJJODRSA-N Ala-Trp-Val Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@H](C)N)=CNC2=C1 XPBVBZPVNFIHOA-UVBJJODRSA-N 0.000 description 1
- AENHOIXXHKNIQL-AUTRQRHGSA-N Ala-Tyr-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]([NH3+])C)CC1=CC=C(O)C=C1 AENHOIXXHKNIQL-AUTRQRHGSA-N 0.000 description 1
- 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 1
- PGNNQOJOEGFAOR-KWQFWETISA-N Ala-Tyr-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 PGNNQOJOEGFAOR-KWQFWETISA-N 0.000 description 1
- GCTANJIJJROSLH-GVARAGBVSA-N Ala-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C)N GCTANJIJJROSLH-GVARAGBVSA-N 0.000 description 1
- VHAQSYHSDKERBS-XPUUQOCRSA-N Ala-Val-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O VHAQSYHSDKERBS-XPUUQOCRSA-N 0.000 description 1
- NLYYHIKRBRMAJV-AEJSXWLSSA-N Ala-Val-Pro Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N NLYYHIKRBRMAJV-AEJSXWLSSA-N 0.000 description 1
- PVSNBTCXCQIXSE-JYJNAYRXSA-N Arg-Arg-Phe Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PVSNBTCXCQIXSE-JYJNAYRXSA-N 0.000 description 1
- RWWPBOUMKFBHAL-FXQIFTODSA-N Arg-Asn-Cys Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(O)=O RWWPBOUMKFBHAL-FXQIFTODSA-N 0.000 description 1
- NONSEUUPKITYQT-BQBZGAKWSA-N Arg-Asn-Gly Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N)CN=C(N)N NONSEUUPKITYQT-BQBZGAKWSA-N 0.000 description 1
- QPOARHANPULOTM-GMOBBJLQSA-N Arg-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N QPOARHANPULOTM-GMOBBJLQSA-N 0.000 description 1
- MAISCYVJLBBRNU-DCAQKATOSA-N Arg-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N MAISCYVJLBBRNU-DCAQKATOSA-N 0.000 description 1
- KWTVWJPNHAOREN-IHRRRGAJSA-N Arg-Asn-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KWTVWJPNHAOREN-IHRRRGAJSA-N 0.000 description 1
- 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 1
- YFBGNGASPGRWEM-DCAQKATOSA-N Arg-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YFBGNGASPGRWEM-DCAQKATOSA-N 0.000 description 1
- JSHVMZANPXCDTL-GMOBBJLQSA-N Arg-Asp-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JSHVMZANPXCDTL-GMOBBJLQSA-N 0.000 description 1
- GDVDRMUYICMNFJ-CIUDSAMLSA-N Arg-Cys-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O GDVDRMUYICMNFJ-CIUDSAMLSA-N 0.000 description 1
- VDBKFYYIBLXEIF-GUBZILKMSA-N Arg-Gln-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VDBKFYYIBLXEIF-GUBZILKMSA-N 0.000 description 1
- RYRQZJVFDVWURI-SRVKXCTJSA-N Arg-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N RYRQZJVFDVWURI-SRVKXCTJSA-N 0.000 description 1
- OHYQKYUTLIPFOX-ZPFDUUQYSA-N Arg-Glu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OHYQKYUTLIPFOX-ZPFDUUQYSA-N 0.000 description 1
- 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 1
- IRRMIGDCPOPZJW-ULQDDVLXSA-N Arg-His-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IRRMIGDCPOPZJW-ULQDDVLXSA-N 0.000 description 1
- NVUIWHJLPSZZQC-CYDGBPFRSA-N Arg-Ile-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NVUIWHJLPSZZQC-CYDGBPFRSA-N 0.000 description 1
- FLYANDHDFRGGTM-PYJNHQTQSA-N Arg-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N FLYANDHDFRGGTM-PYJNHQTQSA-N 0.000 description 1
- FFEUXEAKYRCACT-PEDHHIEDSA-N Arg-Ile-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(O)=O FFEUXEAKYRCACT-PEDHHIEDSA-N 0.000 description 1
- YBZMTKUDWXZLIX-UWVGGRQHSA-N Arg-Leu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YBZMTKUDWXZLIX-UWVGGRQHSA-N 0.000 description 1
- BNYNOWJESJJIOI-XUXIUFHCSA-N Arg-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N BNYNOWJESJJIOI-XUXIUFHCSA-N 0.000 description 1
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 1
- BTJVOUQWFXABOI-IHRRRGAJSA-N Arg-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCNC(N)=N BTJVOUQWFXABOI-IHRRRGAJSA-N 0.000 description 1
- KSUALAGYYLQSHJ-RCWTZXSCSA-N Arg-Met-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSUALAGYYLQSHJ-RCWTZXSCSA-N 0.000 description 1
- FKQITMVNILRUCQ-IHRRRGAJSA-N Arg-Phe-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O FKQITMVNILRUCQ-IHRRRGAJSA-N 0.000 description 1
- UIUXXFIKWQVMEX-UFYCRDLUSA-N Arg-Phe-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UIUXXFIKWQVMEX-UFYCRDLUSA-N 0.000 description 1
- XSPKAHFVDKRGRL-DCAQKATOSA-N Arg-Pro-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XSPKAHFVDKRGRL-DCAQKATOSA-N 0.000 description 1
- STHNZYKCJHWULY-AVGNSLFASA-N Arg-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O STHNZYKCJHWULY-AVGNSLFASA-N 0.000 description 1
- DNLQVHBBMPZUGJ-BQBZGAKWSA-N Arg-Ser-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O DNLQVHBBMPZUGJ-BQBZGAKWSA-N 0.000 description 1
- BECXEHHOZNFFFX-IHRRRGAJSA-N Arg-Ser-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BECXEHHOZNFFFX-IHRRRGAJSA-N 0.000 description 1
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- UZSQXCMNUPKLCC-FJXKBIBVSA-N Arg-Thr-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UZSQXCMNUPKLCC-FJXKBIBVSA-N 0.000 description 1
- KSHJMDSNSKDJPU-QTKMDUPCSA-N Arg-Thr-His Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KSHJMDSNSKDJPU-QTKMDUPCSA-N 0.000 description 1
- YNSUUAOAFCVINY-OSUNSFLBSA-N Arg-Thr-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YNSUUAOAFCVINY-OSUNSFLBSA-N 0.000 description 1
- 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 1
- DRDWXKWUSIKKOB-PJODQICGSA-N Arg-Trp-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O DRDWXKWUSIKKOB-PJODQICGSA-N 0.000 description 1
- ULBHWNVWSCJLCO-NHCYSSNCSA-N Arg-Val-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N ULBHWNVWSCJLCO-NHCYSSNCSA-N 0.000 description 1
- VYZBPPBKFCHCIS-WPRPVWTQSA-N Arg-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N VYZBPPBKFCHCIS-WPRPVWTQSA-N 0.000 description 1
- UTSMXMABBPFVJP-SZMVWBNQSA-N Arg-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UTSMXMABBPFVJP-SZMVWBNQSA-N 0.000 description 1
- PFOYSEIHFVKHNF-FXQIFTODSA-N Asn-Ala-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PFOYSEIHFVKHNF-FXQIFTODSA-N 0.000 description 1
- RZVVKNIACROXRM-ZLUOBGJFSA-N Asn-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N RZVVKNIACROXRM-ZLUOBGJFSA-N 0.000 description 1
- XYOVHPDDWCEUDY-CIUDSAMLSA-N Asn-Ala-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O XYOVHPDDWCEUDY-CIUDSAMLSA-N 0.000 description 1
- SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 1
- DQTIWTULBGLJBL-DCAQKATOSA-N Asn-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)N)N DQTIWTULBGLJBL-DCAQKATOSA-N 0.000 description 1
- VKCOHFFSTKCXEQ-OLHMAJIHSA-N Asn-Asn-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VKCOHFFSTKCXEQ-OLHMAJIHSA-N 0.000 description 1
- QHBMKQWOIYJYMI-BYULHYEWSA-N Asn-Asn-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O QHBMKQWOIYJYMI-BYULHYEWSA-N 0.000 description 1
- WVCJSDCHTUTONA-FXQIFTODSA-N Asn-Asp-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WVCJSDCHTUTONA-FXQIFTODSA-N 0.000 description 1
- XVVOVPFMILMHPX-ZLUOBGJFSA-N Asn-Asp-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XVVOVPFMILMHPX-ZLUOBGJFSA-N 0.000 description 1
- 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 1
- BKDDABUWNKGZCK-XHNCKOQMSA-N Asn-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)N)C(=O)O BKDDABUWNKGZCK-XHNCKOQMSA-N 0.000 description 1
- GFFRWIJAFFMQGM-NUMRIWBASA-N Asn-Glu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFFRWIJAFFMQGM-NUMRIWBASA-N 0.000 description 1
- PBSQFBAJKPLRJY-BYULHYEWSA-N Asn-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N PBSQFBAJKPLRJY-BYULHYEWSA-N 0.000 description 1
- JQSWHKKUZMTOIH-QWRGUYRKSA-N Asn-Gly-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N JQSWHKKUZMTOIH-QWRGUYRKSA-N 0.000 description 1
- OOWSBIOUKIUWLO-RCOVLWMOSA-N Asn-Gly-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O OOWSBIOUKIUWLO-RCOVLWMOSA-N 0.000 description 1
- RAKKBBHMTJSXOY-XVYDVKMFSA-N Asn-His-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O RAKKBBHMTJSXOY-XVYDVKMFSA-N 0.000 description 1
- PTSDPWIHOYMRGR-UGYAYLCHSA-N Asn-Ile-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O PTSDPWIHOYMRGR-UGYAYLCHSA-N 0.000 description 1
- GQRDIVQPSMPQME-ZPFDUUQYSA-N Asn-Ile-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O GQRDIVQPSMPQME-ZPFDUUQYSA-N 0.000 description 1
- YVXRYLVELQYAEQ-SRVKXCTJSA-N Asn-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N YVXRYLVELQYAEQ-SRVKXCTJSA-N 0.000 description 1
- NTWOPSIUJBMNRI-KKUMJFAQSA-N Asn-Lys-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NTWOPSIUJBMNRI-KKUMJFAQSA-N 0.000 description 1
- MYVBTYXSWILFCG-BQBZGAKWSA-N Asn-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)N)N MYVBTYXSWILFCG-BQBZGAKWSA-N 0.000 description 1
- RVHGJNGNKGDCPX-KKUMJFAQSA-N Asn-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N RVHGJNGNKGDCPX-KKUMJFAQSA-N 0.000 description 1
- FTNRWCPWDWRPAV-BZSNNMDCSA-N Asn-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CC(N)=O)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FTNRWCPWDWRPAV-BZSNNMDCSA-N 0.000 description 1
- ZJIFRAPZHAGLGR-MELADBBJSA-N Asn-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(=O)N)N)C(=O)O ZJIFRAPZHAGLGR-MELADBBJSA-N 0.000 description 1
- RBOBTTLFPRSXKZ-BZSNNMDCSA-N Asn-Phe-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RBOBTTLFPRSXKZ-BZSNNMDCSA-N 0.000 description 1
- OOXUBGLNDRGOKT-FXQIFTODSA-N Asn-Ser-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OOXUBGLNDRGOKT-FXQIFTODSA-N 0.000 description 1
- MKJBPDLENBUHQU-CIUDSAMLSA-N Asn-Ser-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O MKJBPDLENBUHQU-CIUDSAMLSA-N 0.000 description 1
- SNYCNNPOFYBCEK-ZLUOBGJFSA-N Asn-Ser-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O SNYCNNPOFYBCEK-ZLUOBGJFSA-N 0.000 description 1
- JBDLMLZNDRLDIX-HJGDQZAQSA-N Asn-Thr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O JBDLMLZNDRLDIX-HJGDQZAQSA-N 0.000 description 1
- XIDSGDJNUJRUHE-VEVYYDQMSA-N Asn-Thr-Met Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O XIDSGDJNUJRUHE-VEVYYDQMSA-N 0.000 description 1
- JZLFYAAGGYMRIK-BYULHYEWSA-N Asn-Val-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O JZLFYAAGGYMRIK-BYULHYEWSA-N 0.000 description 1
- JNCRAQVYJZGIOW-QSFUFRPTSA-N Asn-Val-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JNCRAQVYJZGIOW-QSFUFRPTSA-N 0.000 description 1
- XBQSLMACWDXWLJ-GHCJXIJMSA-N Asp-Ala-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XBQSLMACWDXWLJ-GHCJXIJMSA-N 0.000 description 1
- NECWUSYTYSIFNC-DLOVCJGASA-N Asp-Ala-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 NECWUSYTYSIFNC-DLOVCJGASA-N 0.000 description 1
- 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 1
- IXIWEFWRKIUMQX-DCAQKATOSA-N Asp-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O IXIWEFWRKIUMQX-DCAQKATOSA-N 0.000 description 1
- DBWYWXNMZZYIRY-LPEHRKFASA-N Asp-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O DBWYWXNMZZYIRY-LPEHRKFASA-N 0.000 description 1
- 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 1
- NAPNAGZWHQHZLG-ZLUOBGJFSA-N Asp-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N NAPNAGZWHQHZLG-ZLUOBGJFSA-N 0.000 description 1
- QOVWVLLHMMCFFY-ZLUOBGJFSA-N Asp-Asp-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O QOVWVLLHMMCFFY-ZLUOBGJFSA-N 0.000 description 1
- 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 1
- VHWNKSJHQFZJTH-FXQIFTODSA-N Asp-Asp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N VHWNKSJHQFZJTH-FXQIFTODSA-N 0.000 description 1
- FTNVLGCFIJEMQT-CIUDSAMLSA-N Asp-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N FTNVLGCFIJEMQT-CIUDSAMLSA-N 0.000 description 1
- VHQOCWWKXIOAQI-WDSKDSINSA-N Asp-Gln-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O VHQOCWWKXIOAQI-WDSKDSINSA-N 0.000 description 1
- VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 1
- GHODABZPVZMWCE-FXQIFTODSA-N Asp-Glu-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O GHODABZPVZMWCE-FXQIFTODSA-N 0.000 description 1
- DGKCOYGQLNWNCJ-ACZMJKKPSA-N Asp-Glu-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O DGKCOYGQLNWNCJ-ACZMJKKPSA-N 0.000 description 1
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 1
- PSLSTUMPZILTAH-BYULHYEWSA-N Asp-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PSLSTUMPZILTAH-BYULHYEWSA-N 0.000 description 1
- PZXPWHFYZXTFBI-YUMQZZPRSA-N Asp-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PZXPWHFYZXTFBI-YUMQZZPRSA-N 0.000 description 1
- TZOZNVLBTAFJRW-UGYAYLCHSA-N Asp-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N TZOZNVLBTAFJRW-UGYAYLCHSA-N 0.000 description 1
- KQBVNNAPIURMPD-PEFMBERDSA-N Asp-Ile-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KQBVNNAPIURMPD-PEFMBERDSA-N 0.000 description 1
- NHSDEZURHWEZPN-SXTJYALSSA-N Asp-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H](CC(=O)O)N NHSDEZURHWEZPN-SXTJYALSSA-N 0.000 description 1
- SPKCGKRUYKMDHP-GUDRVLHUSA-N Asp-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N SPKCGKRUYKMDHP-GUDRVLHUSA-N 0.000 description 1
- SPWXXPFDTMYTRI-IUKAMOBKSA-N Asp-Ile-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SPWXXPFDTMYTRI-IUKAMOBKSA-N 0.000 description 1
- RTXQQDVBACBSCW-CFMVVWHZSA-N Asp-Ile-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RTXQQDVBACBSCW-CFMVVWHZSA-N 0.000 description 1
- PAYPSKIBMDHZPI-CIUDSAMLSA-N Asp-Leu-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PAYPSKIBMDHZPI-CIUDSAMLSA-N 0.000 description 1
- AYFVRYXNDHBECD-YUMQZZPRSA-N Asp-Leu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AYFVRYXNDHBECD-YUMQZZPRSA-N 0.000 description 1
- CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 1
- UZFHNLYQWMGUHU-DCAQKATOSA-N Asp-Lys-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UZFHNLYQWMGUHU-DCAQKATOSA-N 0.000 description 1
- HJCGDIGVVWETRO-ZPFDUUQYSA-N Asp-Lys-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(O)=O)C(O)=O HJCGDIGVVWETRO-ZPFDUUQYSA-N 0.000 description 1
- YTXCCDCOHIYQFC-GUBZILKMSA-N Asp-Met-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTXCCDCOHIYQFC-GUBZILKMSA-N 0.000 description 1
- VMVUDJUXJKDGNR-FXQIFTODSA-N Asp-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N VMVUDJUXJKDGNR-FXQIFTODSA-N 0.000 description 1
- BPTFNDRZKBFMTH-DCAQKATOSA-N Asp-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N BPTFNDRZKBFMTH-DCAQKATOSA-N 0.000 description 1
- LKVKODXGSAFOFY-VEVYYDQMSA-N Asp-Met-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LKVKODXGSAFOFY-VEVYYDQMSA-N 0.000 description 1
- YRZIYQGXTSBRLT-AVGNSLFASA-N Asp-Phe-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O YRZIYQGXTSBRLT-AVGNSLFASA-N 0.000 description 1
- PCJOFZYFFMBZKC-PCBIJLKTSA-N Asp-Phe-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PCJOFZYFFMBZKC-PCBIJLKTSA-N 0.000 description 1
- LIQNMKIBMPEOOP-IHRRRGAJSA-N Asp-Phe-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)N LIQNMKIBMPEOOP-IHRRRGAJSA-N 0.000 description 1
- DINOVZWPTMGSRF-QXEWZRGKSA-N Asp-Pro-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O DINOVZWPTMGSRF-QXEWZRGKSA-N 0.000 description 1
- XXAMCEGRCZQGEM-ZLUOBGJFSA-N Asp-Ser-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O XXAMCEGRCZQGEM-ZLUOBGJFSA-N 0.000 description 1
- DRCOAZZDQRCGGP-GHCJXIJMSA-N Asp-Ser-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DRCOAZZDQRCGGP-GHCJXIJMSA-N 0.000 description 1
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 1
- GXHDGYOXPNQCKM-XVSYOHENSA-N Asp-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O GXHDGYOXPNQCKM-XVSYOHENSA-N 0.000 description 1
- 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 1
- LTARLVHGOGBRHN-AAEUAGOBSA-N Asp-Trp-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(O)=O LTARLVHGOGBRHN-AAEUAGOBSA-N 0.000 description 1
- PLNJUJGNLDSFOP-UWJYBYFXSA-N Asp-Tyr-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O PLNJUJGNLDSFOP-UWJYBYFXSA-N 0.000 description 1
- USENATHVGFXRNO-SRVKXCTJSA-N Asp-Tyr-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 USENATHVGFXRNO-SRVKXCTJSA-N 0.000 description 1
- BPAUXFVCSYQDQX-JRQIVUDYSA-N Asp-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(=O)O)N)O BPAUXFVCSYQDQX-JRQIVUDYSA-N 0.000 description 1
- XWKBWZXGNXTDKY-ZKWXMUAHSA-N Asp-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O XWKBWZXGNXTDKY-ZKWXMUAHSA-N 0.000 description 1
- GFYOIYJJMSHLSN-QXEWZRGKSA-N Asp-Val-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GFYOIYJJMSHLSN-QXEWZRGKSA-N 0.000 description 1
- QPDUWAUSSWGJSB-NGZCFLSTSA-N Asp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N QPDUWAUSSWGJSB-NGZCFLSTSA-N 0.000 description 1
- JGLWFWXGOINXEA-YDHLFZDLSA-N Asp-Val-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JGLWFWXGOINXEA-YDHLFZDLSA-N 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 240000002791 Brassica napus Species 0.000 description 1
- 235000006008 Brassica napus var napus Nutrition 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- ASHTVGGFIMESRD-LKXGYXEUSA-N Cys-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N)O ASHTVGGFIMESRD-LKXGYXEUSA-N 0.000 description 1
- UVZFZTWNHOQWNK-NAKRPEOUSA-N Cys-Ile-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UVZFZTWNHOQWNK-NAKRPEOUSA-N 0.000 description 1
- XLLSMEFANRROJE-GUBZILKMSA-N Cys-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N XLLSMEFANRROJE-GUBZILKMSA-N 0.000 description 1
- IZUNQDRIAOLWCN-YUMQZZPRSA-N Cys-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N IZUNQDRIAOLWCN-YUMQZZPRSA-N 0.000 description 1
- CNAMJJOZGXPDHW-IHRRRGAJSA-N Cys-Pro-Phe Chemical compound N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O CNAMJJOZGXPDHW-IHRRRGAJSA-N 0.000 description 1
- RJPKQCFHEPPTGL-ZLUOBGJFSA-N Cys-Ser-Asp Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RJPKQCFHEPPTGL-ZLUOBGJFSA-N 0.000 description 1
- HJXSYJVCMUOUNY-SRVKXCTJSA-N Cys-Ser-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N HJXSYJVCMUOUNY-SRVKXCTJSA-N 0.000 description 1
- ABLQPNMKLMFDQU-BIIVOSGPSA-N Cys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CS)N)C(=O)O ABLQPNMKLMFDQU-BIIVOSGPSA-N 0.000 description 1
- LLUXQOVDMQZMPJ-KKUMJFAQSA-N Cys-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CS)CC1=CC=C(O)C=C1 LLUXQOVDMQZMPJ-KKUMJFAQSA-N 0.000 description 1
- VIOQRFNAZDMVLO-NRPADANISA-N Cys-Val-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VIOQRFNAZDMVLO-NRPADANISA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 description 1
- 229920004943 Delrin® Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000004435 EPR spectroscopy Methods 0.000 description 1
- 101000760806 Eisenia fetida Lysenin Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 101100226347 Escherichia phage lambda exo gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010058643 Fungal Proteins Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- AAOBFSKXAVIORT-GUBZILKMSA-N Gln-Asn-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O AAOBFSKXAVIORT-GUBZILKMSA-N 0.000 description 1
- RBWKVOSARCFSQQ-FXQIFTODSA-N Gln-Gln-Ser Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O RBWKVOSARCFSQQ-FXQIFTODSA-N 0.000 description 1
- PNENQZWRFMUZOM-DCAQKATOSA-N Gln-Glu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O PNENQZWRFMUZOM-DCAQKATOSA-N 0.000 description 1
- DRDSQGHKTLSNEA-GLLZPBPUSA-N Gln-Glu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DRDSQGHKTLSNEA-GLLZPBPUSA-N 0.000 description 1
- XSBGUANSZDGULP-IUCAKERBSA-N Gln-Gly-Lys Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O XSBGUANSZDGULP-IUCAKERBSA-N 0.000 description 1
- SMLDOQHTOAAFJQ-WDSKDSINSA-N Gln-Gly-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SMLDOQHTOAAFJQ-WDSKDSINSA-N 0.000 description 1
- LTXLIIZACMCQTO-GUBZILKMSA-N Gln-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N LTXLIIZACMCQTO-GUBZILKMSA-N 0.000 description 1
- HXOLDXKNWKLDMM-YVNDNENWSA-N Gln-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HXOLDXKNWKLDMM-YVNDNENWSA-N 0.000 description 1
- VZRAXPGTUNDIDK-GUBZILKMSA-N Gln-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VZRAXPGTUNDIDK-GUBZILKMSA-N 0.000 description 1
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 1
- MLSKFHLRFVGNLL-WDCWCFNPSA-N Gln-Leu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MLSKFHLRFVGNLL-WDCWCFNPSA-N 0.000 description 1
- LURQDGKYBFWWJA-MNXVOIDGSA-N Gln-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)N LURQDGKYBFWWJA-MNXVOIDGSA-N 0.000 description 1
- ZXGLLNZQSBLQLT-SRVKXCTJSA-N Gln-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZXGLLNZQSBLQLT-SRVKXCTJSA-N 0.000 description 1
- GQTNWYFWSUFFRA-KKUMJFAQSA-N Gln-Met-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GQTNWYFWSUFFRA-KKUMJFAQSA-N 0.000 description 1
- DOQUICBEISTQHE-CIUDSAMLSA-N Gln-Pro-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O DOQUICBEISTQHE-CIUDSAMLSA-N 0.000 description 1
- OREPWMPAUWIIAM-ZPFDUUQYSA-N Gln-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)N)N OREPWMPAUWIIAM-ZPFDUUQYSA-N 0.000 description 1
- NYCVMJGIJYQWDO-CIUDSAMLSA-N Gln-Ser-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NYCVMJGIJYQWDO-CIUDSAMLSA-N 0.000 description 1
- PAOHIZNRJNIXQY-XQXXSGGOSA-N Gln-Thr-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PAOHIZNRJNIXQY-XQXXSGGOSA-N 0.000 description 1
- UEILCTONAMOGBR-RWRJDSDZSA-N Gln-Thr-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UEILCTONAMOGBR-RWRJDSDZSA-N 0.000 description 1
- NHMRJKKAVMENKJ-WDCWCFNPSA-N Gln-Thr-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NHMRJKKAVMENKJ-WDCWCFNPSA-N 0.000 description 1
- ZFBBMCKQSNJZSN-AUTRQRHGSA-N Gln-Val-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFBBMCKQSNJZSN-AUTRQRHGSA-N 0.000 description 1
- ZMXZGYLINVNTKH-DZKIICNBSA-N Gln-Val-Phe Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZMXZGYLINVNTKH-DZKIICNBSA-N 0.000 description 1
- FITIQFSXXBKFFM-NRPADANISA-N Gln-Val-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FITIQFSXXBKFFM-NRPADANISA-N 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 1
- RLZBLVSJDFHDBL-KBIXCLLPSA-N Glu-Ala-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RLZBLVSJDFHDBL-KBIXCLLPSA-N 0.000 description 1
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 1
- CGYDXNKRIMJMLV-GUBZILKMSA-N Glu-Arg-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CGYDXNKRIMJMLV-GUBZILKMSA-N 0.000 description 1
- VPKBCVUDBNINAH-GARJFASQSA-N Glu-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O VPKBCVUDBNINAH-GARJFASQSA-N 0.000 description 1
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 1
- NADWTMLCUDMDQI-ACZMJKKPSA-N Glu-Asp-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N NADWTMLCUDMDQI-ACZMJKKPSA-N 0.000 description 1
- RTOOAKXIJADOLL-GUBZILKMSA-N Glu-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N RTOOAKXIJADOLL-GUBZILKMSA-N 0.000 description 1
- IESFZVCAVACGPH-PEFMBERDSA-N Glu-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O IESFZVCAVACGPH-PEFMBERDSA-N 0.000 description 1
- JRCUFCXYZLPSDZ-ACZMJKKPSA-N Glu-Asp-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O JRCUFCXYZLPSDZ-ACZMJKKPSA-N 0.000 description 1
- CYHBMLHCQXXCCT-AVGNSLFASA-N Glu-Asp-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CYHBMLHCQXXCCT-AVGNSLFASA-N 0.000 description 1
- XHWLNISLUFEWNS-CIUDSAMLSA-N Glu-Gln-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O XHWLNISLUFEWNS-CIUDSAMLSA-N 0.000 description 1
- UMIRPYLZFKOEOH-YVNDNENWSA-N Glu-Gln-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UMIRPYLZFKOEOH-YVNDNENWSA-N 0.000 description 1
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 1
- SJPMNHCEWPTRBR-BQBZGAKWSA-N Glu-Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SJPMNHCEWPTRBR-BQBZGAKWSA-N 0.000 description 1
- IQACOVZVOMVILH-FXQIFTODSA-N Glu-Glu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O IQACOVZVOMVILH-FXQIFTODSA-N 0.000 description 1
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 1
- QJCKNLPMTPXXEM-AUTRQRHGSA-N Glu-Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O QJCKNLPMTPXXEM-AUTRQRHGSA-N 0.000 description 1
- AIGROOHQXCACHL-WDSKDSINSA-N Glu-Gly-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O AIGROOHQXCACHL-WDSKDSINSA-N 0.000 description 1
- UHVIQGKBMXEVGN-WDSKDSINSA-N Glu-Gly-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O UHVIQGKBMXEVGN-WDSKDSINSA-N 0.000 description 1
- CAVMESABQIKFKT-IUCAKERBSA-N Glu-Gly-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N CAVMESABQIKFKT-IUCAKERBSA-N 0.000 description 1
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 1
- VOORMNJKNBGYGK-YUMQZZPRSA-N Glu-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N VOORMNJKNBGYGK-YUMQZZPRSA-N 0.000 description 1
- XMPAXPSENRSOSV-RYUDHWBXSA-N Glu-Gly-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XMPAXPSENRSOSV-RYUDHWBXSA-N 0.000 description 1
- BRKUZSLQMPNVFN-SRVKXCTJSA-N Glu-His-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BRKUZSLQMPNVFN-SRVKXCTJSA-N 0.000 description 1
- DVLZZEPUNFEUBW-AVGNSLFASA-N Glu-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N DVLZZEPUNFEUBW-AVGNSLFASA-N 0.000 description 1
- QIQABBIDHGQXGA-ZPFDUUQYSA-N Glu-Ile-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QIQABBIDHGQXGA-ZPFDUUQYSA-N 0.000 description 1
- BKRQSECBKKCCKW-HVTMNAMFSA-N Glu-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N BKRQSECBKKCCKW-HVTMNAMFSA-N 0.000 description 1
- VSRCAOIHMGCIJK-SRVKXCTJSA-N Glu-Leu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VSRCAOIHMGCIJK-SRVKXCTJSA-N 0.000 description 1
- PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 description 1
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 1
- IVGJYOOGJLFKQE-AVGNSLFASA-N Glu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N IVGJYOOGJLFKQE-AVGNSLFASA-N 0.000 description 1
- IOUQWHIEQYQVFD-JYJNAYRXSA-N Glu-Leu-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IOUQWHIEQYQVFD-JYJNAYRXSA-N 0.000 description 1
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 1
- SJJHXJDSNQJMMW-SRVKXCTJSA-N Glu-Lys-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O SJJHXJDSNQJMMW-SRVKXCTJSA-N 0.000 description 1
- YGLCLCMAYUYZSG-AVGNSLFASA-N Glu-Lys-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 YGLCLCMAYUYZSG-AVGNSLFASA-N 0.000 description 1
- ILWHFUZZCFYSKT-AVGNSLFASA-N Glu-Lys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ILWHFUZZCFYSKT-AVGNSLFASA-N 0.000 description 1
- FMBWLLMUPXTXFC-SDDRHHMPSA-N Glu-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)N)C(=O)O FMBWLLMUPXTXFC-SDDRHHMPSA-N 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- AQNYKMCFCCZEEL-JYJNAYRXSA-N Glu-Lys-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AQNYKMCFCCZEEL-JYJNAYRXSA-N 0.000 description 1
- ZQYZDDXTNQXUJH-CIUDSAMLSA-N Glu-Met-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)N ZQYZDDXTNQXUJH-CIUDSAMLSA-N 0.000 description 1
- UERORLSAFUHDGU-AVGNSLFASA-N Glu-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UERORLSAFUHDGU-AVGNSLFASA-N 0.000 description 1
- JZJGEKDPWVJOLD-QEWYBTABSA-N Glu-Phe-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JZJGEKDPWVJOLD-QEWYBTABSA-N 0.000 description 1
- QNJNPKSWAHPYGI-JYJNAYRXSA-N Glu-Phe-Leu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 QNJNPKSWAHPYGI-JYJNAYRXSA-N 0.000 description 1
- DXVOKNVIKORTHQ-GUBZILKMSA-N Glu-Pro-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O DXVOKNVIKORTHQ-GUBZILKMSA-N 0.000 description 1
- QOXDAWODGSIDDI-GUBZILKMSA-N Glu-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N QOXDAWODGSIDDI-GUBZILKMSA-N 0.000 description 1
- CQGBSALYGOXQPE-HTUGSXCWSA-N Glu-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O CQGBSALYGOXQPE-HTUGSXCWSA-N 0.000 description 1
- CAQXJMUDOLSBPF-SUSMZKCASA-N Glu-Thr-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAQXJMUDOLSBPF-SUSMZKCASA-N 0.000 description 1
- MIWJDJAMMKHUAR-ZVZYQTTQSA-N Glu-Trp-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCC(=O)O)N MIWJDJAMMKHUAR-ZVZYQTTQSA-N 0.000 description 1
- UUTGYDAKPISJAO-JYJNAYRXSA-N Glu-Tyr-Leu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 UUTGYDAKPISJAO-JYJNAYRXSA-N 0.000 description 1
- QEJKKJNDDDPSMU-KKUMJFAQSA-N Glu-Tyr-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCSC)C(O)=O QEJKKJNDDDPSMU-KKUMJFAQSA-N 0.000 description 1
- MLILEEIVMRUYBX-NHCYSSNCSA-N Glu-Val-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MLILEEIVMRUYBX-NHCYSSNCSA-N 0.000 description 1
- YPHPEHMXOYTEQG-LAEOZQHASA-N Glu-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O YPHPEHMXOYTEQG-LAEOZQHASA-N 0.000 description 1
- LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 description 1
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 1
- FGGKGJHCVMYGCD-UKJIMTQDSA-N Glu-Val-Ile 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)CC)C(O)=O FGGKGJHCVMYGCD-UKJIMTQDSA-N 0.000 description 1
- 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 1
- BRFJMRSRMOMIMU-WHFBIAKZSA-N Gly-Ala-Asn Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O BRFJMRSRMOMIMU-WHFBIAKZSA-N 0.000 description 1
- VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 1
- QSDKBRMVXSWAQE-BFHQHQDPSA-N Gly-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN QSDKBRMVXSWAQE-BFHQHQDPSA-N 0.000 description 1
- LERGJIVJIIODPZ-ZANVPECISA-N Gly-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)CN)C)C(O)=O)=CNC2=C1 LERGJIVJIIODPZ-ZANVPECISA-N 0.000 description 1
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 1
- GGEJHJIXRBTJPD-BYPYZUCNSA-N Gly-Asn-Gly Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GGEJHJIXRBTJPD-BYPYZUCNSA-N 0.000 description 1
- FMNHBTKMRFVGRO-FOHZUACHSA-N Gly-Asn-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CN FMNHBTKMRFVGRO-FOHZUACHSA-N 0.000 description 1
- XBWMTPAIUQIWKA-BYULHYEWSA-N Gly-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN XBWMTPAIUQIWKA-BYULHYEWSA-N 0.000 description 1
- VUUOMYFPWDYETE-WDSKDSINSA-N Gly-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN VUUOMYFPWDYETE-WDSKDSINSA-N 0.000 description 1
- AQLHORCVPGXDJW-IUCAKERBSA-N Gly-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN AQLHORCVPGXDJW-IUCAKERBSA-N 0.000 description 1
- MOJKRXIRAZPZLW-WDSKDSINSA-N Gly-Glu-Ala Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O MOJKRXIRAZPZLW-WDSKDSINSA-N 0.000 description 1
- HDNXXTBKOJKWNN-WDSKDSINSA-N Gly-Glu-Asn Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O HDNXXTBKOJKWNN-WDSKDSINSA-N 0.000 description 1
- BEQGFMIBZFNROK-JGVFFNPUSA-N Gly-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)CN)C(=O)O BEQGFMIBZFNROK-JGVFFNPUSA-N 0.000 description 1
- JSNNHGHYGYMVCK-XVKPBYJWSA-N Gly-Glu-Val Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JSNNHGHYGYMVCK-XVKPBYJWSA-N 0.000 description 1
- CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 1
- GDOZQTNZPCUARW-YFKPBYRVSA-N Gly-Gly-Glu Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O GDOZQTNZPCUARW-YFKPBYRVSA-N 0.000 description 1
- PDAWDNVHMUKWJR-ZETCQYMHSA-N Gly-Gly-His Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 PDAWDNVHMUKWJR-ZETCQYMHSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 1
- LPCKHUXOGVNZRS-YUMQZZPRSA-N Gly-His-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O LPCKHUXOGVNZRS-YUMQZZPRSA-N 0.000 description 1
- YNIMVVJTPWCUJH-KBPBESRZSA-N Gly-His-Tyr Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YNIMVVJTPWCUJH-KBPBESRZSA-N 0.000 description 1
- ITZOBNKQDZEOCE-NHCYSSNCSA-N Gly-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)CN ITZOBNKQDZEOCE-NHCYSSNCSA-N 0.000 description 1
- XVYKMNXXJXQKME-XEGUGMAKSA-N Gly-Ile-Tyr Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XVYKMNXXJXQKME-XEGUGMAKSA-N 0.000 description 1
- NSTUFLGQJCOCDL-UWVGGRQHSA-N Gly-Leu-Arg Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NSTUFLGQJCOCDL-UWVGGRQHSA-N 0.000 description 1
- YTSVAIMKVLZUDU-YUMQZZPRSA-N Gly-Leu-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YTSVAIMKVLZUDU-YUMQZZPRSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- LIXWIUAORXJNBH-QWRGUYRKSA-N Gly-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN LIXWIUAORXJNBH-QWRGUYRKSA-N 0.000 description 1
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 1
- FHQRLHFYVZAQHU-IUCAKERBSA-N Gly-Lys-Gln Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O FHQRLHFYVZAQHU-IUCAKERBSA-N 0.000 description 1
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 1
- FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 description 1
- CVFOYJJOZYYEPE-KBPBESRZSA-N Gly-Lys-Tyr Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CVFOYJJOZYYEPE-KBPBESRZSA-N 0.000 description 1
- OQQKUTVULYLCDG-ONGXEEELSA-N Gly-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CN)C(O)=O OQQKUTVULYLCDG-ONGXEEELSA-N 0.000 description 1
- BBTCXWTXOXUNFX-IUCAKERBSA-N Gly-Met-Arg Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O BBTCXWTXOXUNFX-IUCAKERBSA-N 0.000 description 1
- QGDOOCIPHSSADO-STQMWFEESA-N Gly-Met-Phe Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QGDOOCIPHSSADO-STQMWFEESA-N 0.000 description 1
- UWQDKRIZSROAKS-FJXKBIBVSA-N Gly-Met-Thr Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWQDKRIZSROAKS-FJXKBIBVSA-N 0.000 description 1
- WMGHDYWNHNLGBV-ONGXEEELSA-N Gly-Phe-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 WMGHDYWNHNLGBV-ONGXEEELSA-N 0.000 description 1
- WZSHYFGOLPXPLL-RYUDHWBXSA-N Gly-Phe-Glu Chemical compound NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(O)=O)C(O)=O WZSHYFGOLPXPLL-RYUDHWBXSA-N 0.000 description 1
- YLEIWGJJBFBFHC-KBPBESRZSA-N Gly-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 YLEIWGJJBFBFHC-KBPBESRZSA-N 0.000 description 1
- QAMMIGULQSIRCD-IRXDYDNUSA-N Gly-Phe-Tyr Chemical compound C([C@H](NC(=O)C[NH3+])C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)C1=CC=CC=C1 QAMMIGULQSIRCD-IRXDYDNUSA-N 0.000 description 1
- GGLIDLCEPDHEJO-BQBZGAKWSA-N Gly-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)CN GGLIDLCEPDHEJO-BQBZGAKWSA-N 0.000 description 1
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 1
- CSMYMGFCEJWALV-WDSKDSINSA-N Gly-Ser-Gln Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O CSMYMGFCEJWALV-WDSKDSINSA-N 0.000 description 1
- ABPRMMYHROQBLY-NKWVEPMBSA-N Gly-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)CN)C(=O)O ABPRMMYHROQBLY-NKWVEPMBSA-N 0.000 description 1
- NVTPVQLIZCOJFK-FOHZUACHSA-N Gly-Thr-Asp Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O NVTPVQLIZCOJFK-FOHZUACHSA-N 0.000 description 1
- CQMFNTVQVLQRLT-JHEQGTHGSA-N Gly-Thr-Gln Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O CQMFNTVQVLQRLT-JHEQGTHGSA-N 0.000 description 1
- DBUNZBWUWCIELX-JHEQGTHGSA-N Gly-Thr-Glu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O DBUNZBWUWCIELX-JHEQGTHGSA-N 0.000 description 1
- RHRLHXQWHCNJKR-PMVVWTBXSA-N Gly-Thr-His Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 RHRLHXQWHCNJKR-PMVVWTBXSA-N 0.000 description 1
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 1
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 1
- CUVBTVWFVIIDOC-YEPSODPASA-N Gly-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)CN CUVBTVWFVIIDOC-YEPSODPASA-N 0.000 description 1
- JKSMZVCGQWVTBW-STQMWFEESA-N Gly-Trp-Asn Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O JKSMZVCGQWVTBW-STQMWFEESA-N 0.000 description 1
- UIQGJYUEQDOODF-KWQFWETISA-N Gly-Tyr-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 UIQGJYUEQDOODF-KWQFWETISA-N 0.000 description 1
- UVTSZKIATYSKIR-RYUDHWBXSA-N Gly-Tyr-Glu Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O UVTSZKIATYSKIR-RYUDHWBXSA-N 0.000 description 1
- OCRQUYDOYKCOQG-IRXDYDNUSA-N Gly-Tyr-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 OCRQUYDOYKCOQG-IRXDYDNUSA-N 0.000 description 1
- JYGYNWYVKXENNE-OALUTQOASA-N Gly-Tyr-Trp Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JYGYNWYVKXENNE-OALUTQOASA-N 0.000 description 1
- NGBGZCUWFVVJKC-IRXDYDNUSA-N Gly-Tyr-Tyr Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NGBGZCUWFVVJKC-IRXDYDNUSA-N 0.000 description 1
- GJHWILMUOANXTG-WPRPVWTQSA-N Gly-Val-Arg Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GJHWILMUOANXTG-WPRPVWTQSA-N 0.000 description 1
- YDIDLLVFCYSXNY-RCOVLWMOSA-N Gly-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN YDIDLLVFCYSXNY-RCOVLWMOSA-N 0.000 description 1
- KSOBNUBCYHGUKH-UWVGGRQHSA-N Gly-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN KSOBNUBCYHGUKH-UWVGGRQHSA-N 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- VSLXGYMEHVAJBH-DLOVCJGASA-N His-Ala-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O VSLXGYMEHVAJBH-DLOVCJGASA-N 0.000 description 1
- SYMSVYVUSPSAAO-IHRRRGAJSA-N His-Arg-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O SYMSVYVUSPSAAO-IHRRRGAJSA-N 0.000 description 1
- MWAJSVTZZOUOBU-IHRRRGAJSA-N His-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC1=CN=CN1 MWAJSVTZZOUOBU-IHRRRGAJSA-N 0.000 description 1
- JWTKVPMQCCRPQY-SRVKXCTJSA-N His-Asn-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JWTKVPMQCCRPQY-SRVKXCTJSA-N 0.000 description 1
- IMCHNUANCIGUKS-SRVKXCTJSA-N His-Glu-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IMCHNUANCIGUKS-SRVKXCTJSA-N 0.000 description 1
- HQKADFMLECZIQJ-HVTMNAMFSA-N His-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CN=CN1)N HQKADFMLECZIQJ-HVTMNAMFSA-N 0.000 description 1
- CNHSMSFYVARZLI-YJRXYDGGSA-N His-His-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CNHSMSFYVARZLI-YJRXYDGGSA-N 0.000 description 1
- OQDLKDUVMTUPPG-AVGNSLFASA-N His-Leu-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O OQDLKDUVMTUPPG-AVGNSLFASA-N 0.000 description 1
- LVWIJITYHRZHBO-IXOXFDKPSA-N His-Leu-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LVWIJITYHRZHBO-IXOXFDKPSA-N 0.000 description 1
- JUIOPCXACJLRJK-AVGNSLFASA-N His-Lys-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N JUIOPCXACJLRJK-AVGNSLFASA-N 0.000 description 1
- UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 description 1
- DGLAHESNTJWGDO-SRVKXCTJSA-N His-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N DGLAHESNTJWGDO-SRVKXCTJSA-N 0.000 description 1
- CUEQQFOGARVNHU-VGDYDELISA-N His-Ser-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUEQQFOGARVNHU-VGDYDELISA-N 0.000 description 1
- UOYGZBIPZYKGSH-SRVKXCTJSA-N His-Ser-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N UOYGZBIPZYKGSH-SRVKXCTJSA-N 0.000 description 1
- XVZJRZQIHJMUBG-TUBUOCAGSA-N His-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC1=CN=CN1)N XVZJRZQIHJMUBG-TUBUOCAGSA-N 0.000 description 1
- VXZZUXWAOMWWJH-QTKMDUPCSA-N His-Thr-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O VXZZUXWAOMWWJH-QTKMDUPCSA-N 0.000 description 1
- XGBVLRJLHUVCNK-DCAQKATOSA-N His-Val-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O XGBVLRJLHUVCNK-DCAQKATOSA-N 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- HDOYNXLPTRQLAD-JBDRJPRFSA-N Ile-Ala-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)O)N HDOYNXLPTRQLAD-JBDRJPRFSA-N 0.000 description 1
- CYHYBSGMHMHKOA-CIQUZCHMSA-N Ile-Ala-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CYHYBSGMHMHKOA-CIQUZCHMSA-N 0.000 description 1
- FVEWRQXNISSYFO-ZPFDUUQYSA-N Ile-Arg-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N FVEWRQXNISSYFO-ZPFDUUQYSA-N 0.000 description 1
- CWJQMCPYXNVMBS-STECZYCISA-N Ile-Arg-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N CWJQMCPYXNVMBS-STECZYCISA-N 0.000 description 1
- UAVQIQOOBXFKRC-BYULHYEWSA-N Ile-Asn-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O UAVQIQOOBXFKRC-BYULHYEWSA-N 0.000 description 1
- FJWYJQRCVNGEAQ-ZPFDUUQYSA-N Ile-Asn-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N FJWYJQRCVNGEAQ-ZPFDUUQYSA-N 0.000 description 1
- UKTUOMWSJPXODT-GUDRVLHUSA-N Ile-Asn-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N UKTUOMWSJPXODT-GUDRVLHUSA-N 0.000 description 1
- QYOGJYIRKACXEP-SLBDDTMCSA-N Ile-Asn-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N QYOGJYIRKACXEP-SLBDDTMCSA-N 0.000 description 1
- BGZIJZJBXRVBGJ-SXTJYALSSA-N Ile-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N BGZIJZJBXRVBGJ-SXTJYALSSA-N 0.000 description 1
- QSPLUJGYOPZINY-ZPFDUUQYSA-N Ile-Asp-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N QSPLUJGYOPZINY-ZPFDUUQYSA-N 0.000 description 1
- ZGGWRNBSBOHIGH-HVTMNAMFSA-N Ile-Gln-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ZGGWRNBSBOHIGH-HVTMNAMFSA-N 0.000 description 1
- DMZOUKXXHJQPTL-GRLWGSQLSA-N Ile-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N DMZOUKXXHJQPTL-GRLWGSQLSA-N 0.000 description 1
- JDAWAWXGAUZPNJ-ZPFDUUQYSA-N Ile-Glu-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N JDAWAWXGAUZPNJ-ZPFDUUQYSA-N 0.000 description 1
- NZOCIWKZUVUNDW-ZKWXMUAHSA-N Ile-Gly-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O NZOCIWKZUVUNDW-ZKWXMUAHSA-N 0.000 description 1
- CDGLBYSAZFIIJO-RCOVLWMOSA-N Ile-Gly-Gly Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O CDGLBYSAZFIIJO-RCOVLWMOSA-N 0.000 description 1
- MQFGXJNSUJTXDT-QSFUFRPTSA-N Ile-Gly-Ile Chemical compound N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)O MQFGXJNSUJTXDT-QSFUFRPTSA-N 0.000 description 1
- PDTMWFVVNZYWTR-NHCYSSNCSA-N Ile-Gly-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O PDTMWFVVNZYWTR-NHCYSSNCSA-N 0.000 description 1
- LBRCLQMZAHRTLV-ZKWXMUAHSA-N Ile-Gly-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LBRCLQMZAHRTLV-ZKWXMUAHSA-N 0.000 description 1
- TWPSALMCEHCIOY-YTFOTSKYSA-N Ile-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)O)N TWPSALMCEHCIOY-YTFOTSKYSA-N 0.000 description 1
- PFPUFNLHBXKPHY-HTFCKZLJSA-N Ile-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)O)N PFPUFNLHBXKPHY-HTFCKZLJSA-N 0.000 description 1
- KBAPKNDWAGVGTH-IGISWZIWSA-N Ile-Ile-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 KBAPKNDWAGVGTH-IGISWZIWSA-N 0.000 description 1
- QZZIBQZLWBOOJH-PEDHHIEDSA-N Ile-Ile-Val Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)O QZZIBQZLWBOOJH-PEDHHIEDSA-N 0.000 description 1
- UIEZQYNXCYHMQS-BJDJZHNGSA-N Ile-Lys-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)O)N UIEZQYNXCYHMQS-BJDJZHNGSA-N 0.000 description 1
- RMNMUUCYTMLWNA-ZPFDUUQYSA-N Ile-Lys-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RMNMUUCYTMLWNA-ZPFDUUQYSA-N 0.000 description 1
- PNTWNAXGBOZMBO-MNXVOIDGSA-N Ile-Lys-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PNTWNAXGBOZMBO-MNXVOIDGSA-N 0.000 description 1
- XDUVMJCBYUKNFJ-MXAVVETBSA-N Ile-Lys-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N XDUVMJCBYUKNFJ-MXAVVETBSA-N 0.000 description 1
- AKOYRLRUFBZOSP-BJDJZHNGSA-N Ile-Lys-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N AKOYRLRUFBZOSP-BJDJZHNGSA-N 0.000 description 1
- UDBPXJNOEWDBDF-XUXIUFHCSA-N Ile-Lys-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)O)N UDBPXJNOEWDBDF-XUXIUFHCSA-N 0.000 description 1
- FJWALBCCVIHZBS-QXEWZRGKSA-N Ile-Met-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)O)N FJWALBCCVIHZBS-QXEWZRGKSA-N 0.000 description 1
- BATWGBRIZANGPN-ZPFDUUQYSA-N Ile-Pro-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)N)C(=O)O)N BATWGBRIZANGPN-ZPFDUUQYSA-N 0.000 description 1
- YKZAMJXNJUWFIK-JBDRJPRFSA-N Ile-Ser-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)O)N YKZAMJXNJUWFIK-JBDRJPRFSA-N 0.000 description 1
- JNLSTRPWUXOORL-MMWGEVLESA-N Ile-Ser-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N JNLSTRPWUXOORL-MMWGEVLESA-N 0.000 description 1
- HXIDVIFHRYRXLZ-NAKRPEOUSA-N Ile-Ser-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)O)N HXIDVIFHRYRXLZ-NAKRPEOUSA-N 0.000 description 1
- HJDZMPFEXINXLO-QPHKQPEJSA-N Ile-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N HJDZMPFEXINXLO-QPHKQPEJSA-N 0.000 description 1
- QGXQHJQPAPMACW-PPCPHDFISA-N Ile-Thr-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)O)N QGXQHJQPAPMACW-PPCPHDFISA-N 0.000 description 1
- HQLSBZFLOUHQJK-STECZYCISA-N Ile-Tyr-Arg Chemical compound CC[C@H](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 HQLSBZFLOUHQJK-STECZYCISA-N 0.000 description 1
- OMDWJWGZGMCQND-CFMVVWHZSA-N Ile-Tyr-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N OMDWJWGZGMCQND-CFMVVWHZSA-N 0.000 description 1
- BCISUQVFDGYZBO-QSFUFRPTSA-N Ile-Val-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O BCISUQVFDGYZBO-QSFUFRPTSA-N 0.000 description 1
- WIYDLTIBHZSPKY-HJWJTTGWSA-N Ile-Val-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WIYDLTIBHZSPKY-HJWJTTGWSA-N 0.000 description 1
- RQZFWBLDTBDEOF-RNJOBUHISA-N Ile-Val-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N RQZFWBLDTBDEOF-RNJOBUHISA-N 0.000 description 1
- JZBVBOKASHNXAD-NAKRPEOUSA-N Ile-Val-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N JZBVBOKASHNXAD-NAKRPEOUSA-N 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 1
- 240000004322 Lens culinaris Species 0.000 description 1
- 235000014647 Lens culinaris subsp culinaris Nutrition 0.000 description 1
- CZCSUZMIRKFFFA-CIUDSAMLSA-N Leu-Ala-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O CZCSUZMIRKFFFA-CIUDSAMLSA-N 0.000 description 1
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 1
- WNGVUZWBXZKQES-YUMQZZPRSA-N Leu-Ala-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O WNGVUZWBXZKQES-YUMQZZPRSA-N 0.000 description 1
- DQPQTXMIRBUWKO-DCAQKATOSA-N Leu-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(C)C)N DQPQTXMIRBUWKO-DCAQKATOSA-N 0.000 description 1
- WSGXUIQTEZDVHJ-GARJFASQSA-N Leu-Ala-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O WSGXUIQTEZDVHJ-GARJFASQSA-N 0.000 description 1
- HXWALXSAVBLTPK-NUTKFTJISA-N Leu-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(C)C)N HXWALXSAVBLTPK-NUTKFTJISA-N 0.000 description 1
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 1
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 1
- FJUKMPUELVROGK-IHRRRGAJSA-N Leu-Arg-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N FJUKMPUELVROGK-IHRRRGAJSA-N 0.000 description 1
- QUAAUWNLWMLERT-IHRRRGAJSA-N Leu-Arg-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O QUAAUWNLWMLERT-IHRRRGAJSA-N 0.000 description 1
- 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 1
- IBMVEYRWAWIOTN-RWMBFGLXSA-N Leu-Arg-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(O)=O IBMVEYRWAWIOTN-RWMBFGLXSA-N 0.000 description 1
- UCOCBWDBHCUPQP-DCAQKATOSA-N Leu-Arg-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O UCOCBWDBHCUPQP-DCAQKATOSA-N 0.000 description 1
- KTFHTMHHKXUYPW-ZPFDUUQYSA-N Leu-Asp-Ile 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)CC)C(O)=O KTFHTMHHKXUYPW-ZPFDUUQYSA-N 0.000 description 1
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 description 1
- VPKIQULSKFVCSM-SRVKXCTJSA-N Leu-Gln-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VPKIQULSKFVCSM-SRVKXCTJSA-N 0.000 description 1
- DLCXCECTCPKKCD-GUBZILKMSA-N Leu-Gln-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O DLCXCECTCPKKCD-GUBZILKMSA-N 0.000 description 1
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 1
- LLBQJYDYOLIQAI-JYJNAYRXSA-N Leu-Glu-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LLBQJYDYOLIQAI-JYJNAYRXSA-N 0.000 description 1
- FMEICTQWUKNAGC-YUMQZZPRSA-N Leu-Gly-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O FMEICTQWUKNAGC-YUMQZZPRSA-N 0.000 description 1
- HYIFFZAQXPUEAU-QWRGUYRKSA-N Leu-Gly-Leu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C HYIFFZAQXPUEAU-QWRGUYRKSA-N 0.000 description 1
- UCDHVOALNXENLC-KBPBESRZSA-N Leu-Gly-Tyr Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 UCDHVOALNXENLC-KBPBESRZSA-N 0.000 description 1
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 1
- 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 1
- AUBMZAMQCOYSIC-MNXVOIDGSA-N Leu-Ile-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O AUBMZAMQCOYSIC-MNXVOIDGSA-N 0.000 description 1
- LIINDKYIGYTDLG-PPCPHDFISA-N Leu-Ile-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LIINDKYIGYTDLG-PPCPHDFISA-N 0.000 description 1
- DSFYPIUSAMSERP-IHRRRGAJSA-N Leu-Leu-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DSFYPIUSAMSERP-IHRRRGAJSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 1
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 1
- HVHRPWQEQHIQJF-AVGNSLFASA-N Leu-Lys-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HVHRPWQEQHIQJF-AVGNSLFASA-N 0.000 description 1
- LZHJZLHSRGWBBE-IHRRRGAJSA-N Leu-Lys-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LZHJZLHSRGWBBE-IHRRRGAJSA-N 0.000 description 1
- HDHQQEDVWQGBEE-DCAQKATOSA-N Leu-Met-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(O)=O HDHQQEDVWQGBEE-DCAQKATOSA-N 0.000 description 1
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-N 0.000 description 1
- INCJJHQRZGQLFC-KBPBESRZSA-N Leu-Phe-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O INCJJHQRZGQLFC-KBPBESRZSA-N 0.000 description 1
- WMIOEVKKYIMVKI-DCAQKATOSA-N Leu-Pro-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WMIOEVKKYIMVKI-DCAQKATOSA-N 0.000 description 1
- XWEVVRRSIOBJOO-SRVKXCTJSA-N Leu-Pro-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O XWEVVRRSIOBJOO-SRVKXCTJSA-N 0.000 description 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-N 0.000 description 1
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 1
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 description 1
- MVHXGBZUJLWZOH-BJDJZHNGSA-N Leu-Ser-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MVHXGBZUJLWZOH-BJDJZHNGSA-N 0.000 description 1
- LJBVRCDPWOJOEK-PPCPHDFISA-N Leu-Thr-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LJBVRCDPWOJOEK-PPCPHDFISA-N 0.000 description 1
- CNWDWAMPKVYJJB-NUTKFTJISA-N Leu-Trp-Ala Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 CNWDWAMPKVYJJB-NUTKFTJISA-N 0.000 description 1
- VJGQRELPQWNURN-JYJNAYRXSA-N Leu-Tyr-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O VJGQRELPQWNURN-JYJNAYRXSA-N 0.000 description 1
- JGKHAFUAPZCCDU-BZSNNMDCSA-N Leu-Tyr-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CC=C(O)C=C1 JGKHAFUAPZCCDU-BZSNNMDCSA-N 0.000 description 1
- BTEMNFBEAAOGBR-BZSNNMDCSA-N Leu-Tyr-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BTEMNFBEAAOGBR-BZSNNMDCSA-N 0.000 description 1
- RDFIVFHPOSOXMW-ACRUOGEOSA-N Leu-Tyr-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RDFIVFHPOSOXMW-ACRUOGEOSA-N 0.000 description 1
- AXVIGSRGTMNSJU-YESZJQIVSA-N Leu-Tyr-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N AXVIGSRGTMNSJU-YESZJQIVSA-N 0.000 description 1
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 1
- CGHXMODRYJISSK-NHCYSSNCSA-N Leu-Val-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O CGHXMODRYJISSK-NHCYSSNCSA-N 0.000 description 1
- TUIOUEWKFFVNLH-DCAQKATOSA-N Leu-Val-Cys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O TUIOUEWKFFVNLH-DCAQKATOSA-N 0.000 description 1
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 1
- JCFYLFOCALSNLQ-GUBZILKMSA-N Lys-Ala-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JCFYLFOCALSNLQ-GUBZILKMSA-N 0.000 description 1
- PNPYKQFJGRFYJE-GUBZILKMSA-N Lys-Ala-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNPYKQFJGRFYJE-GUBZILKMSA-N 0.000 description 1
- NFLFJGGKOHYZJF-BJDJZHNGSA-N Lys-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN NFLFJGGKOHYZJF-BJDJZHNGSA-N 0.000 description 1
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 1
- WXJKFRMKJORORD-DCAQKATOSA-N Lys-Arg-Ala Chemical compound NC(=N)NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CCCCN WXJKFRMKJORORD-DCAQKATOSA-N 0.000 description 1
- GQUDMNDPQTXZRV-DCAQKATOSA-N Lys-Arg-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GQUDMNDPQTXZRV-DCAQKATOSA-N 0.000 description 1
- JGAMUXDWYSXYLM-SRVKXCTJSA-N Lys-Arg-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O JGAMUXDWYSXYLM-SRVKXCTJSA-N 0.000 description 1
- VHNOAIFVYUQOOY-XUXIUFHCSA-N Lys-Arg-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VHNOAIFVYUQOOY-XUXIUFHCSA-N 0.000 description 1
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 1
- DGAAQRAUOFHBFJ-CIUDSAMLSA-N Lys-Asn-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O DGAAQRAUOFHBFJ-CIUDSAMLSA-N 0.000 description 1
- DNEJSAIMVANNPA-DCAQKATOSA-N Lys-Asn-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DNEJSAIMVANNPA-DCAQKATOSA-N 0.000 description 1
- 108010062166 Lys-Asn-Asp Proteins 0.000 description 1
- BYPMOIFBQPEWOH-CIUDSAMLSA-N Lys-Asn-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N BYPMOIFBQPEWOH-CIUDSAMLSA-N 0.000 description 1
- LZWNAOIMTLNMDW-NHCYSSNCSA-N Lys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N LZWNAOIMTLNMDW-NHCYSSNCSA-N 0.000 description 1
- WGCKDDHUFPQSMZ-ZPFDUUQYSA-N Lys-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCCCN WGCKDDHUFPQSMZ-ZPFDUUQYSA-N 0.000 description 1
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 1
- ZAWOJFFMBANLGE-CIUDSAMLSA-N Lys-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N ZAWOJFFMBANLGE-CIUDSAMLSA-N 0.000 description 1
- KSFQPRLZAUXXPT-GARJFASQSA-N Lys-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N)C(=O)O KSFQPRLZAUXXPT-GARJFASQSA-N 0.000 description 1
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 1
- KZOHPCYVORJBLG-AVGNSLFASA-N Lys-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N KZOHPCYVORJBLG-AVGNSLFASA-N 0.000 description 1
- VEGLGAOVLFODGC-GUBZILKMSA-N Lys-Glu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VEGLGAOVLFODGC-GUBZILKMSA-N 0.000 description 1
- WGLAORUKDGRINI-WDCWCFNPSA-N Lys-Glu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGLAORUKDGRINI-WDCWCFNPSA-N 0.000 description 1
- QZONCCHVHCOBSK-YUMQZZPRSA-N Lys-Gly-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O QZONCCHVHCOBSK-YUMQZZPRSA-N 0.000 description 1
- JZMGVXLDOQOKAH-UWVGGRQHSA-N Lys-Gly-Met Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O JZMGVXLDOQOKAH-UWVGGRQHSA-N 0.000 description 1
- ZMMDPRTXLAEMOD-BZSNNMDCSA-N Lys-His-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZMMDPRTXLAEMOD-BZSNNMDCSA-N 0.000 description 1
- IVFUVMSKSFSFBT-NHCYSSNCSA-N Lys-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN IVFUVMSKSFSFBT-NHCYSSNCSA-N 0.000 description 1
- JYXBNQOKPRQNQS-YTFOTSKYSA-N Lys-Ile-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JYXBNQOKPRQNQS-YTFOTSKYSA-N 0.000 description 1
- ZXFRGTAIIZHNHG-AJNGGQMLSA-N Lys-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N ZXFRGTAIIZHNHG-AJNGGQMLSA-N 0.000 description 1
- QOJDBRUCOXQSSK-AJNGGQMLSA-N Lys-Ile-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(O)=O QOJDBRUCOXQSSK-AJNGGQMLSA-N 0.000 description 1
- OVAOHZIOUBEQCJ-IHRRRGAJSA-N Lys-Leu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OVAOHZIOUBEQCJ-IHRRRGAJSA-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
- RBEATVHTWHTHTJ-KKUMJFAQSA-N Lys-Leu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O RBEATVHTWHTHTJ-KKUMJFAQSA-N 0.000 description 1
- 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 1
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 1
- OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 1
- 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 1
- GAHJXEMYXKLZRQ-AJNGGQMLSA-N Lys-Lys-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O GAHJXEMYXKLZRQ-AJNGGQMLSA-N 0.000 description 1
- QQPSCXKFDSORFT-IHRRRGAJSA-N Lys-Lys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN QQPSCXKFDSORFT-IHRRRGAJSA-N 0.000 description 1
- GZGWILAQHOVXTD-DCAQKATOSA-N Lys-Met-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O GZGWILAQHOVXTD-DCAQKATOSA-N 0.000 description 1
- MTBBHUKKPWKXBT-ULQDDVLXSA-N Lys-Met-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MTBBHUKKPWKXBT-ULQDDVLXSA-N 0.000 description 1
- XFOAWKDQMRMCDN-ULQDDVLXSA-N Lys-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)CC1=CC=CC=C1 XFOAWKDQMRMCDN-ULQDDVLXSA-N 0.000 description 1
- LUAJJLPHUXPQLH-KKUMJFAQSA-N Lys-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N LUAJJLPHUXPQLH-KKUMJFAQSA-N 0.000 description 1
- WLXGMVVHTIUPHE-ULQDDVLXSA-N Lys-Phe-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O WLXGMVVHTIUPHE-ULQDDVLXSA-N 0.000 description 1
- BOJYMMBYBNOOGG-DCAQKATOSA-N Lys-Pro-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O BOJYMMBYBNOOGG-DCAQKATOSA-N 0.000 description 1
- YSPZCHGIWAQVKQ-AVGNSLFASA-N Lys-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN YSPZCHGIWAQVKQ-AVGNSLFASA-N 0.000 description 1
- HKXSZKJMDBHOTG-CIUDSAMLSA-N Lys-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN HKXSZKJMDBHOTG-CIUDSAMLSA-N 0.000 description 1
- GHKXHCMRAUYLBS-CIUDSAMLSA-N Lys-Ser-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O GHKXHCMRAUYLBS-CIUDSAMLSA-N 0.000 description 1
- DNWBUCHHMRQWCZ-GUBZILKMSA-N Lys-Ser-Gln Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O DNWBUCHHMRQWCZ-GUBZILKMSA-N 0.000 description 1
- DIBZLYZXTSVGLN-CIUDSAMLSA-N Lys-Ser-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O DIBZLYZXTSVGLN-CIUDSAMLSA-N 0.000 description 1
- PLOUVAYOMTYJRG-JXUBOQSCSA-N Lys-Thr-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PLOUVAYOMTYJRG-JXUBOQSCSA-N 0.000 description 1
- AWMMBHDKERMOID-YTQUADARSA-N Lys-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CCCCN)N)C(=O)O AWMMBHDKERMOID-YTQUADARSA-N 0.000 description 1
- MIMXMVDLMDMOJD-BZSNNMDCSA-N Lys-Tyr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O MIMXMVDLMDMOJD-BZSNNMDCSA-N 0.000 description 1
- BWECSLVQIWEMSC-IHRRRGAJSA-N Lys-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCCN)N BWECSLVQIWEMSC-IHRRRGAJSA-N 0.000 description 1
- TXTZMVNJIRZABH-ULQDDVLXSA-N Lys-Val-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 TXTZMVNJIRZABH-ULQDDVLXSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 244000070406 Malus silvestris Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- VHGIWFGJIHTASW-FXQIFTODSA-N Met-Ala-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O VHGIWFGJIHTASW-FXQIFTODSA-N 0.000 description 1
- ONGCSGVHCSAATF-CIUDSAMLSA-N Met-Ala-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O ONGCSGVHCSAATF-CIUDSAMLSA-N 0.000 description 1
- GAELMDJMQDUDLJ-BQBZGAKWSA-N Met-Ala-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O GAELMDJMQDUDLJ-BQBZGAKWSA-N 0.000 description 1
- QAHFGYLFLVGBNW-DCAQKATOSA-N Met-Ala-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN QAHFGYLFLVGBNW-DCAQKATOSA-N 0.000 description 1
- WXHHTBVYQOSYSL-FXQIFTODSA-N Met-Ala-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O WXHHTBVYQOSYSL-FXQIFTODSA-N 0.000 description 1
- DLAFCQWUMFMZSN-GUBZILKMSA-N Met-Arg-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CCCN=C(N)N DLAFCQWUMFMZSN-GUBZILKMSA-N 0.000 description 1
- QXEVZBXTDTVPCP-GMOBBJLQSA-N Met-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCSC)N QXEVZBXTDTVPCP-GMOBBJLQSA-N 0.000 description 1
- GODBLDDYHFTUAH-CIUDSAMLSA-N Met-Asp-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O GODBLDDYHFTUAH-CIUDSAMLSA-N 0.000 description 1
- FVKRQMQQFGBXHV-QXEWZRGKSA-N Met-Asp-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FVKRQMQQFGBXHV-QXEWZRGKSA-N 0.000 description 1
- XBYKTPZCWQQSGB-IHRRRGAJSA-N Met-Cys-Tyr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBYKTPZCWQQSGB-IHRRRGAJSA-N 0.000 description 1
- KQBJYJXPZBNEIK-DCAQKATOSA-N Met-Glu-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQBJYJXPZBNEIK-DCAQKATOSA-N 0.000 description 1
- AETNZPKUUYYYEK-CIUDSAMLSA-N Met-Glu-Asn Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O AETNZPKUUYYYEK-CIUDSAMLSA-N 0.000 description 1
- VZBXCMCHIHEPBL-SRVKXCTJSA-N Met-Glu-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN VZBXCMCHIHEPBL-SRVKXCTJSA-N 0.000 description 1
- GVIVXNFKJQFTCE-YUMQZZPRSA-N Met-Gly-Gln Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O GVIVXNFKJQFTCE-YUMQZZPRSA-N 0.000 description 1
- BMHIFARYXOJDLD-WPRPVWTQSA-N Met-Gly-Val Chemical compound [H]N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O BMHIFARYXOJDLD-WPRPVWTQSA-N 0.000 description 1
- CUICVBQQHMKBRJ-LSJOCFKGSA-N Met-His-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](C)C(O)=O CUICVBQQHMKBRJ-LSJOCFKGSA-N 0.000 description 1
- RRIHXWPHQSXHAQ-XUXIUFHCSA-N Met-Ile-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(O)=O RRIHXWPHQSXHAQ-XUXIUFHCSA-N 0.000 description 1
- HGAJNEWOUHDUMZ-SRVKXCTJSA-N Met-Leu-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O HGAJNEWOUHDUMZ-SRVKXCTJSA-N 0.000 description 1
- SODXFJOPSCXOHE-IHRRRGAJSA-N Met-Leu-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O SODXFJOPSCXOHE-IHRRRGAJSA-N 0.000 description 1
- WPTHAGXMYDRPFD-SRVKXCTJSA-N Met-Lys-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O WPTHAGXMYDRPFD-SRVKXCTJSA-N 0.000 description 1
- UFOWQBYMUILSRK-IHRRRGAJSA-N Met-Lys-His Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 UFOWQBYMUILSRK-IHRRRGAJSA-N 0.000 description 1
- ZRACLHJYVRBJFC-ULQDDVLXSA-N Met-Lys-Phe Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZRACLHJYVRBJFC-ULQDDVLXSA-N 0.000 description 1
- IRVONVRHHJXWTK-RWMBFGLXSA-N Met-Lys-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N IRVONVRHHJXWTK-RWMBFGLXSA-N 0.000 description 1
- VAGCEUUEMMXFEX-GUBZILKMSA-N Met-Met-Asn Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(O)=O VAGCEUUEMMXFEX-GUBZILKMSA-N 0.000 description 1
- LLKWSEXLNFBKIF-CYDGBPFRSA-N Met-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CCSC LLKWSEXLNFBKIF-CYDGBPFRSA-N 0.000 description 1
- PHKBGZKVOJCIMZ-SRVKXCTJSA-N Met-Pro-Arg Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PHKBGZKVOJCIMZ-SRVKXCTJSA-N 0.000 description 1
- YLDSJJOGQNEQJK-AVGNSLFASA-N Met-Pro-Leu Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YLDSJJOGQNEQJK-AVGNSLFASA-N 0.000 description 1
- SOAYQFDWEIWPPR-IHRRRGAJSA-N Met-Ser-Tyr Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O SOAYQFDWEIWPPR-IHRRRGAJSA-N 0.000 description 1
- FXBKQTOGURNXSL-HJGDQZAQSA-N Met-Thr-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(O)=O FXBKQTOGURNXSL-HJGDQZAQSA-N 0.000 description 1
- NDJSSFWDYDUQID-YTWAJWBKSA-N Met-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCSC)N)O NDJSSFWDYDUQID-YTWAJWBKSA-N 0.000 description 1
- 241000361919 Metaphire sieboldi Species 0.000 description 1
- 241001074893 Methanococci Species 0.000 description 1
- 241001148031 Methanococcoides burtonii Species 0.000 description 1
- 240000005561 Musa balbisiana Species 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 108010087066 N2-tryptophyllysine Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- BJEYSVHMGIJORT-NHCYSSNCSA-N Phe-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BJEYSVHMGIJORT-NHCYSSNCSA-N 0.000 description 1
- JNRFYJZCMHHGMH-UBHSHLNASA-N Phe-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 JNRFYJZCMHHGMH-UBHSHLNASA-N 0.000 description 1
- AYPMIIKUMNADSU-IHRRRGAJSA-N Phe-Arg-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O AYPMIIKUMNADSU-IHRRRGAJSA-N 0.000 description 1
- MQWISMJKHOUEMW-ULQDDVLXSA-N Phe-Arg-His Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 MQWISMJKHOUEMW-ULQDDVLXSA-N 0.000 description 1
- LGBVMDMZZFYSFW-HJWJTTGWSA-N Phe-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CC=CC=C1)N LGBVMDMZZFYSFW-HJWJTTGWSA-N 0.000 description 1
- AGYXCMYVTBYGCT-ULQDDVLXSA-N Phe-Arg-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O AGYXCMYVTBYGCT-ULQDDVLXSA-N 0.000 description 1
- HCTXJGRYAACKOB-SRVKXCTJSA-N Phe-Asn-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N HCTXJGRYAACKOB-SRVKXCTJSA-N 0.000 description 1
- KIAWKQJTSGRCSA-AVGNSLFASA-N Phe-Asn-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KIAWKQJTSGRCSA-AVGNSLFASA-N 0.000 description 1
- WGXOKDLDIWSOCV-MELADBBJSA-N Phe-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O WGXOKDLDIWSOCV-MELADBBJSA-N 0.000 description 1
- UEEVBGHEGJMDDV-AVGNSLFASA-N Phe-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 UEEVBGHEGJMDDV-AVGNSLFASA-N 0.000 description 1
- DDYIRGBOZVKRFR-AVGNSLFASA-N Phe-Asp-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N DDYIRGBOZVKRFR-AVGNSLFASA-N 0.000 description 1
- CSYVXYQDIVCQNU-QWRGUYRKSA-N Phe-Asp-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O CSYVXYQDIVCQNU-QWRGUYRKSA-N 0.000 description 1
- DJPXNKUDJKGQEE-BZSNNMDCSA-N Phe-Asp-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O DJPXNKUDJKGQEE-BZSNNMDCSA-N 0.000 description 1
- CUMXHKAOHNWRFQ-BZSNNMDCSA-N Phe-Asp-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 CUMXHKAOHNWRFQ-BZSNNMDCSA-N 0.000 description 1
- HOYQLNNGMHXZDW-KKUMJFAQSA-N Phe-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HOYQLNNGMHXZDW-KKUMJFAQSA-N 0.000 description 1
- MGECUMGTSHYHEJ-QEWYBTABSA-N Phe-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 MGECUMGTSHYHEJ-QEWYBTABSA-N 0.000 description 1
- KJJROSNFBRWPHS-JYJNAYRXSA-N Phe-Glu-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KJJROSNFBRWPHS-JYJNAYRXSA-N 0.000 description 1
- BFYHIHGIHGROAT-HTUGSXCWSA-N Phe-Glu-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BFYHIHGIHGROAT-HTUGSXCWSA-N 0.000 description 1
- ZLGQEBCCANLYRA-RYUDHWBXSA-N Phe-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O ZLGQEBCCANLYRA-RYUDHWBXSA-N 0.000 description 1
- HGNGAMWHGGANAU-WHOFXGATSA-N Phe-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 HGNGAMWHGGANAU-WHOFXGATSA-N 0.000 description 1
- VJLLEKDQJSMHRU-STQMWFEESA-N Phe-Gly-Met Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O VJLLEKDQJSMHRU-STQMWFEESA-N 0.000 description 1
- FXYXBEZMRACDDR-KKUMJFAQSA-N Phe-His-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O FXYXBEZMRACDDR-KKUMJFAQSA-N 0.000 description 1
- NAOVYENZCWFBDG-BZSNNMDCSA-N Phe-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 NAOVYENZCWFBDG-BZSNNMDCSA-N 0.000 description 1
- BVHFFNYBKRTSIU-MEYUZBJRSA-N Phe-His-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BVHFFNYBKRTSIU-MEYUZBJRSA-N 0.000 description 1
- ONORAGIFHNAADN-LLLHUVSDSA-N Phe-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N ONORAGIFHNAADN-LLLHUVSDSA-N 0.000 description 1
- RSPUIENXSJYZQO-JYJNAYRXSA-N Phe-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 RSPUIENXSJYZQO-JYJNAYRXSA-N 0.000 description 1
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 1
- OQTDZEJJWWAGJT-KKUMJFAQSA-N Phe-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O OQTDZEJJWWAGJT-KKUMJFAQSA-N 0.000 description 1
- MJAYDXWQQUOURZ-JYJNAYRXSA-N Phe-Lys-Gln Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O MJAYDXWQQUOURZ-JYJNAYRXSA-N 0.000 description 1
- JKJSIYKSGIDHPM-WBAXXEDZSA-N Phe-Phe-Ala Chemical compound C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O JKJSIYKSGIDHPM-WBAXXEDZSA-N 0.000 description 1
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 1
- ZVRJWDUPIDMHDN-ULQDDVLXSA-N Phe-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 ZVRJWDUPIDMHDN-ULQDDVLXSA-N 0.000 description 1
- JHSRGEODDALISP-XVSYOHENSA-N Phe-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O JHSRGEODDALISP-XVSYOHENSA-N 0.000 description 1
- CXMSESHALPOLRE-MEYUZBJRSA-N Phe-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N)O CXMSESHALPOLRE-MEYUZBJRSA-N 0.000 description 1
- VFDRDMOMHBJGKD-UFYCRDLUSA-N Phe-Tyr-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N VFDRDMOMHBJGKD-UFYCRDLUSA-N 0.000 description 1
- CVAUVSOFHJKCHN-BZSNNMDCSA-N Phe-Tyr-Cys Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(O)=O)C1=CC=CC=C1 CVAUVSOFHJKCHN-BZSNNMDCSA-N 0.000 description 1
- NHHZWPNMYQUNEH-ACRUOGEOSA-N Phe-Tyr-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N NHHZWPNMYQUNEH-ACRUOGEOSA-N 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- IFMDQWDAJUMMJC-DCAQKATOSA-N Pro-Ala-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O IFMDQWDAJUMMJC-DCAQKATOSA-N 0.000 description 1
- XQLBWXHVZVBNJM-FXQIFTODSA-N Pro-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 XQLBWXHVZVBNJM-FXQIFTODSA-N 0.000 description 1
- OCSACVPBMIYNJE-GUBZILKMSA-N Pro-Arg-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O OCSACVPBMIYNJE-GUBZILKMSA-N 0.000 description 1
- VCYJKOLZYPYGJV-AVGNSLFASA-N Pro-Arg-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VCYJKOLZYPYGJV-AVGNSLFASA-N 0.000 description 1
- XZGWNSIRZIUHHP-SRVKXCTJSA-N Pro-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1 XZGWNSIRZIUHHP-SRVKXCTJSA-N 0.000 description 1
- SWXSLPHTJVAWDF-VEVYYDQMSA-N Pro-Asn-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWXSLPHTJVAWDF-VEVYYDQMSA-N 0.000 description 1
- XKHCJJPNXFBADI-DCAQKATOSA-N Pro-Asp-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O XKHCJJPNXFBADI-DCAQKATOSA-N 0.000 description 1
- XUSDDSLCRPUKLP-QXEWZRGKSA-N Pro-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 XUSDDSLCRPUKLP-QXEWZRGKSA-N 0.000 description 1
- UPJGUQPLYWTISV-GUBZILKMSA-N Pro-Gln-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UPJGUQPLYWTISV-GUBZILKMSA-N 0.000 description 1
- LHALYDBUDCWMDY-CIUDSAMLSA-N Pro-Glu-Ala Chemical compound C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O LHALYDBUDCWMDY-CIUDSAMLSA-N 0.000 description 1
- KIPIKSXPPLABPN-CIUDSAMLSA-N Pro-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 KIPIKSXPPLABPN-CIUDSAMLSA-N 0.000 description 1
- LGSANCBHSMDFDY-GARJFASQSA-N Pro-Glu-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O LGSANCBHSMDFDY-GARJFASQSA-N 0.000 description 1
- LXVLKXPFIDDHJG-CIUDSAMLSA-N Pro-Glu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O LXVLKXPFIDDHJG-CIUDSAMLSA-N 0.000 description 1
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 1
- ULIWFCCJIOEHMU-BQBZGAKWSA-N Pro-Gly-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 ULIWFCCJIOEHMU-BQBZGAKWSA-N 0.000 description 1
- UIMCLYYSUCIUJM-UWVGGRQHSA-N Pro-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 UIMCLYYSUCIUJM-UWVGGRQHSA-N 0.000 description 1
- IBGCFJDLCYTKPW-NAKRPEOUSA-N Pro-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 IBGCFJDLCYTKPW-NAKRPEOUSA-N 0.000 description 1
- XYHMFGGWNOFUOU-QXEWZRGKSA-N Pro-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 XYHMFGGWNOFUOU-QXEWZRGKSA-N 0.000 description 1
- LXLFEIHKWGHJJB-XUXIUFHCSA-N Pro-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 LXLFEIHKWGHJJB-XUXIUFHCSA-N 0.000 description 1
- KLSOMAFWRISSNI-OSUNSFLBSA-N Pro-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 KLSOMAFWRISSNI-OSUNSFLBSA-N 0.000 description 1
- FYPGHGXAOZTOBO-IHRRRGAJSA-N Pro-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@@H]2CCCN2 FYPGHGXAOZTOBO-IHRRRGAJSA-N 0.000 description 1
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 1
- SRBFGSGDNNQABI-FHWLQOOXSA-N Pro-Leu-Trp Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(=O)[C@@H]1CCCN1 SRBFGSGDNNQABI-FHWLQOOXSA-N 0.000 description 1
- SUENWIFTSTWUKD-AVGNSLFASA-N Pro-Leu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O SUENWIFTSTWUKD-AVGNSLFASA-N 0.000 description 1
- INDVYIOKMXFQFM-SRVKXCTJSA-N Pro-Lys-Gln Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O INDVYIOKMXFQFM-SRVKXCTJSA-N 0.000 description 1
- DWGFLKQSGRUQTI-IHRRRGAJSA-N Pro-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 DWGFLKQSGRUQTI-IHRRRGAJSA-N 0.000 description 1
- SPLBRAKYXGOFSO-UNQGMJICSA-N Pro-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]2CCCN2)O SPLBRAKYXGOFSO-UNQGMJICSA-N 0.000 description 1
- FYKUEXMZYFIZKA-DCAQKATOSA-N Pro-Pro-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O FYKUEXMZYFIZKA-DCAQKATOSA-N 0.000 description 1
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 1
- LNICFEXCAHIJOR-DCAQKATOSA-N Pro-Ser-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LNICFEXCAHIJOR-DCAQKATOSA-N 0.000 description 1
- QUBVFEANYYWBTM-VEVYYDQMSA-N Pro-Thr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O QUBVFEANYYWBTM-VEVYYDQMSA-N 0.000 description 1
- FDMCIBSQRKFSTJ-RHYQMDGZSA-N Pro-Thr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O FDMCIBSQRKFSTJ-RHYQMDGZSA-N 0.000 description 1
- RMJZWERKFFNNNS-XGEHTFHBSA-N Pro-Thr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMJZWERKFFNNNS-XGEHTFHBSA-N 0.000 description 1
- YHUBAXGAAYULJY-ULQDDVLXSA-N Pro-Tyr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O YHUBAXGAAYULJY-ULQDDVLXSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- IIRBTQHFVNGPMQ-AVGNSLFASA-N Pro-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 IIRBTQHFVNGPMQ-AVGNSLFASA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108010079005 RDV peptide Proteins 0.000 description 1
- 101710086015 RNA ligase Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- SRTCFKGBYBZRHA-ACZMJKKPSA-N Ser-Ala-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SRTCFKGBYBZRHA-ACZMJKKPSA-N 0.000 description 1
- IDCKUIWEIZYVSO-WFBYXXMGSA-N Ser-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C)C(O)=O)=CNC2=C1 IDCKUIWEIZYVSO-WFBYXXMGSA-N 0.000 description 1
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 1
- SFZKGGOGCNQPJY-CIUDSAMLSA-N Ser-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N SFZKGGOGCNQPJY-CIUDSAMLSA-N 0.000 description 1
- BTPAWKABYQMKKN-LKXGYXEUSA-N Ser-Asp-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BTPAWKABYQMKKN-LKXGYXEUSA-N 0.000 description 1
- KCFKKAQKRZBWJB-ZLUOBGJFSA-N Ser-Cys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O KCFKKAQKRZBWJB-ZLUOBGJFSA-N 0.000 description 1
- 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 1
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 1
- BRIZMMZEYSAKJX-QEJZJMRPSA-N Ser-Glu-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N BRIZMMZEYSAKJX-QEJZJMRPSA-N 0.000 description 1
- WBINSDOPZHQPPM-AVGNSLFASA-N Ser-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)O WBINSDOPZHQPPM-AVGNSLFASA-N 0.000 description 1
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 1
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 1
- OQPNSDWGAMFJNU-QWRGUYRKSA-N Ser-Gly-Tyr Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OQPNSDWGAMFJNU-QWRGUYRKSA-N 0.000 description 1
- FYUIFUJFNCLUIX-XVYDVKMFSA-N Ser-His-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O FYUIFUJFNCLUIX-XVYDVKMFSA-N 0.000 description 1
- HMRAQFJFTOLDKW-GUBZILKMSA-N Ser-His-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMRAQFJFTOLDKW-GUBZILKMSA-N 0.000 description 1
- IFPBAGJBHSNYPR-ZKWXMUAHSA-N Ser-Ile-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O IFPBAGJBHSNYPR-ZKWXMUAHSA-N 0.000 description 1
- MQQBBLVOUUJKLH-HJPIBITLSA-N Ser-Ile-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MQQBBLVOUUJKLH-HJPIBITLSA-N 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- ZIFYDQAFEMIZII-GUBZILKMSA-N Ser-Leu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZIFYDQAFEMIZII-GUBZILKMSA-N 0.000 description 1
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 1
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- VZQRNAYURWAEFE-KKUMJFAQSA-N Ser-Leu-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VZQRNAYURWAEFE-KKUMJFAQSA-N 0.000 description 1
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 1
- IXZHZUGGKLRHJD-DCAQKATOSA-N Ser-Leu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IXZHZUGGKLRHJD-DCAQKATOSA-N 0.000 description 1
- GVMUJUPXFQFBBZ-GUBZILKMSA-N Ser-Lys-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GVMUJUPXFQFBBZ-GUBZILKMSA-N 0.000 description 1
- LRWBCWGEUCKDTN-BJDJZHNGSA-N Ser-Lys-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LRWBCWGEUCKDTN-BJDJZHNGSA-N 0.000 description 1
- FPCGZYMRFFIYIH-CIUDSAMLSA-N Ser-Lys-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O FPCGZYMRFFIYIH-CIUDSAMLSA-N 0.000 description 1
- XNXRTQZTFVMJIJ-DCAQKATOSA-N Ser-Met-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNXRTQZTFVMJIJ-DCAQKATOSA-N 0.000 description 1
- JJUNLJTUIKFPRF-BPUTZDHNSA-N Ser-Met-Trp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CO)N JJUNLJTUIKFPRF-BPUTZDHNSA-N 0.000 description 1
- GZGFSPWOMUKKCV-NAKRPEOUSA-N Ser-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO GZGFSPWOMUKKCV-NAKRPEOUSA-N 0.000 description 1
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 1
- ILZAUMFXKSIUEF-SRVKXCTJSA-N Ser-Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ILZAUMFXKSIUEF-SRVKXCTJSA-N 0.000 description 1
- XQJCEKXQUJQNNK-ZLUOBGJFSA-N Ser-Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O XQJCEKXQUJQNNK-ZLUOBGJFSA-N 0.000 description 1
- RXUOAOOZIWABBW-XGEHTFHBSA-N Ser-Thr-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RXUOAOOZIWABBW-XGEHTFHBSA-N 0.000 description 1
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 1
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 1
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 1
- VLMIUSLQONKLDV-HEIBUPTGSA-N Ser-Thr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VLMIUSLQONKLDV-HEIBUPTGSA-N 0.000 description 1
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 1
- YXEYTHXDRDAIOJ-CWRNSKLLSA-N Ser-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CO)N)C(=O)O YXEYTHXDRDAIOJ-CWRNSKLLSA-N 0.000 description 1
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 1
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 1
- BEBVVQPDSHHWQL-NRPADANISA-N Ser-Val-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O BEBVVQPDSHHWQL-NRPADANISA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- LSHUNRICNSEEAN-BPUTZDHNSA-N Ser-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CO)N LSHUNRICNSEEAN-BPUTZDHNSA-N 0.000 description 1
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- NJEMRSFGDNECGF-GCJQMDKQSA-N Thr-Ala-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O NJEMRSFGDNECGF-GCJQMDKQSA-N 0.000 description 1
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 1
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 1
- XSLXHSYIVPGEER-KZVJFYERSA-N Thr-Ala-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XSLXHSYIVPGEER-KZVJFYERSA-N 0.000 description 1
- LHUBVKCLOVALIA-HJGDQZAQSA-N Thr-Arg-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O LHUBVKCLOVALIA-HJGDQZAQSA-N 0.000 description 1
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 1
- LXWZOMSOUAMOIA-JIOCBJNQSA-N Thr-Asn-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O LXWZOMSOUAMOIA-JIOCBJNQSA-N 0.000 description 1
- GKMYGVQDGVYCPC-IUKAMOBKSA-N Thr-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)N GKMYGVQDGVYCPC-IUKAMOBKSA-N 0.000 description 1
- NLSNVZAREYQMGR-HJGDQZAQSA-N Thr-Asp-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NLSNVZAREYQMGR-HJGDQZAQSA-N 0.000 description 1
- OHAJHDJOCKKJLV-LKXGYXEUSA-N Thr-Asp-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O OHAJHDJOCKKJLV-LKXGYXEUSA-N 0.000 description 1
- XDARBNMYXKUFOJ-GSSVUCPTSA-N Thr-Asp-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XDARBNMYXKUFOJ-GSSVUCPTSA-N 0.000 description 1
- ZLNWJMRLHLGKFX-SVSWQMSJSA-N Thr-Cys-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZLNWJMRLHLGKFX-SVSWQMSJSA-N 0.000 description 1
- JMGJDTNUMAZNLX-RWRJDSDZSA-N Thr-Glu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JMGJDTNUMAZNLX-RWRJDSDZSA-N 0.000 description 1
- LHEZGZQRLDBSRR-WDCWCFNPSA-N Thr-Glu-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LHEZGZQRLDBSRR-WDCWCFNPSA-N 0.000 description 1
- 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 1
- 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 1
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 1
- ZBKDBZUTTXINIX-RWRJDSDZSA-N Thr-Ile-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZBKDBZUTTXINIX-RWRJDSDZSA-N 0.000 description 1
- 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 1
- YJCVECXVYHZOBK-KNZXXDILSA-N Thr-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H]([C@@H](C)O)N YJCVECXVYHZOBK-KNZXXDILSA-N 0.000 description 1
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 1
- AMXMBCAXAZUCFA-RHYQMDGZSA-N Thr-Leu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMXMBCAXAZUCFA-RHYQMDGZSA-N 0.000 description 1
- KRDSCBLRHORMRK-JXUBOQSCSA-N Thr-Lys-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O KRDSCBLRHORMRK-JXUBOQSCSA-N 0.000 description 1
- DXPURPNJDFCKKO-RHYQMDGZSA-N Thr-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O DXPURPNJDFCKKO-RHYQMDGZSA-N 0.000 description 1
- WNQJTLATMXYSEL-OEAJRASXSA-N Thr-Phe-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WNQJTLATMXYSEL-OEAJRASXSA-N 0.000 description 1
- BDYBHQWMHYDRKJ-UNQGMJICSA-N Thr-Phe-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)O)N)O BDYBHQWMHYDRKJ-UNQGMJICSA-N 0.000 description 1
- NWECYMJLJGCBOD-UNQGMJICSA-N Thr-Phe-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O NWECYMJLJGCBOD-UNQGMJICSA-N 0.000 description 1
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 1
- PRTHQBSMXILLPC-XGEHTFHBSA-N Thr-Ser-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PRTHQBSMXILLPC-XGEHTFHBSA-N 0.000 description 1
- WPSKTVVMQCXPRO-BWBBJGPYSA-N Thr-Ser-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WPSKTVVMQCXPRO-BWBBJGPYSA-N 0.000 description 1
- RVMNUBQWPVOUKH-HEIBUPTGSA-N Thr-Ser-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMNUBQWPVOUKH-HEIBUPTGSA-N 0.000 description 1
- GQPQJNMVELPZNQ-GBALPHGKSA-N Thr-Ser-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O GQPQJNMVELPZNQ-GBALPHGKSA-N 0.000 description 1
- NDZYTIMDOZMECO-SHGPDSBTSA-N Thr-Thr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O NDZYTIMDOZMECO-SHGPDSBTSA-N 0.000 description 1
- UQCNIMDPYICBTR-KYNKHSRBSA-N Thr-Thr-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UQCNIMDPYICBTR-KYNKHSRBSA-N 0.000 description 1
- NLWDSYKZUPRMBJ-IEGACIPQSA-N Thr-Trp-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O NLWDSYKZUPRMBJ-IEGACIPQSA-N 0.000 description 1
- BZTSQFWJNJYZSX-JRQIVUDYSA-N Thr-Tyr-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O BZTSQFWJNJYZSX-JRQIVUDYSA-N 0.000 description 1
- XGFYGMKZKFRGAI-RCWTZXSCSA-N Thr-Val-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N XGFYGMKZKFRGAI-RCWTZXSCSA-N 0.000 description 1
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 1
- VYVBSMCZNHOZGD-RCWTZXSCSA-N Thr-Val-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O VYVBSMCZNHOZGD-RCWTZXSCSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- QAXCHNZDPLSFPC-PJODQICGSA-N Trp-Ala-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 QAXCHNZDPLSFPC-PJODQICGSA-N 0.000 description 1
- MJBBMTOGSOSAKJ-HJXMPXNTSA-N Trp-Ala-Ile Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MJBBMTOGSOSAKJ-HJXMPXNTSA-N 0.000 description 1
- PEYSVKMXSLPQRU-FJHTZYQYSA-N Trp-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O PEYSVKMXSLPQRU-FJHTZYQYSA-N 0.000 description 1
- LCPVBXOHXMBLFW-JSGCOSHPSA-N Trp-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)=CNC2=C1 LCPVBXOHXMBLFW-JSGCOSHPSA-N 0.000 description 1
- GTNCSPKYWCJZAC-XIRDDKMYSA-N Trp-Asp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N GTNCSPKYWCJZAC-XIRDDKMYSA-N 0.000 description 1
- MDDYTWOFHZFABW-SZMVWBNQSA-N Trp-Gln-Leu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O)=CNC2=C1 MDDYTWOFHZFABW-SZMVWBNQSA-N 0.000 description 1
- ZJKZLNAECPIUTL-JBACZVJFSA-N Trp-Gln-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 ZJKZLNAECPIUTL-JBACZVJFSA-N 0.000 description 1
- RPVDDQYNBOVWLR-HOCLYGCPSA-N Trp-Gly-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O RPVDDQYNBOVWLR-HOCLYGCPSA-N 0.000 description 1
- NESIQDDPEFTWAH-BPUTZDHNSA-N Trp-Met-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O NESIQDDPEFTWAH-BPUTZDHNSA-N 0.000 description 1
- GQEXFCQNAJHJTI-IHPCNDPISA-N Trp-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](CC2=CNC3=CC=CC=C32)N GQEXFCQNAJHJTI-IHPCNDPISA-N 0.000 description 1
- JDWUNEPOEZAZGD-BVSLBCMMSA-N Trp-Phe-Met Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=CC=C1 JDWUNEPOEZAZGD-BVSLBCMMSA-N 0.000 description 1
- IVBJBFSWJDNQFW-XIRDDKMYSA-N Trp-Pro-Glu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IVBJBFSWJDNQFW-XIRDDKMYSA-N 0.000 description 1
- SUEGAFMNTXXNLR-WFBYXXMGSA-N Trp-Ser-Ala Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O SUEGAFMNTXXNLR-WFBYXXMGSA-N 0.000 description 1
- ITUAVBRBGKVBLH-BVSLBCMMSA-N Trp-Tyr-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N ITUAVBRBGKVBLH-BVSLBCMMSA-N 0.000 description 1
- UIRVSEPRMWDVEW-RNXOBYDBSA-N Trp-Tyr-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)N UIRVSEPRMWDVEW-RNXOBYDBSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- TVOGEPLDNYTAHD-CQDKDKBSSA-N Tyr-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TVOGEPLDNYTAHD-CQDKDKBSSA-N 0.000 description 1
- HSVPZJLMPLMPOX-BPNCWPANSA-N Tyr-Arg-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O HSVPZJLMPLMPOX-BPNCWPANSA-N 0.000 description 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- DKKHULUSOSWGHS-UWJYBYFXSA-N Tyr-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N DKKHULUSOSWGHS-UWJYBYFXSA-N 0.000 description 1
- ZNFPUOSTMUMUDR-JRQIVUDYSA-N Tyr-Asn-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZNFPUOSTMUMUDR-JRQIVUDYSA-N 0.000 description 1
- BARBHMSSVWPKPZ-IHRRRGAJSA-N Tyr-Asp-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BARBHMSSVWPKPZ-IHRRRGAJSA-N 0.000 description 1
- BEIGSKUPTIFYRZ-SRVKXCTJSA-N Tyr-Asp-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O BEIGSKUPTIFYRZ-SRVKXCTJSA-N 0.000 description 1
- JWHOIHCOHMZSAR-QWRGUYRKSA-N Tyr-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JWHOIHCOHMZSAR-QWRGUYRKSA-N 0.000 description 1
- RCLOWEZASFJFEX-KKUMJFAQSA-N Tyr-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RCLOWEZASFJFEX-KKUMJFAQSA-N 0.000 description 1
- YLRLHDFMMWDYTK-KKUMJFAQSA-N Tyr-Cys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLRLHDFMMWDYTK-KKUMJFAQSA-N 0.000 description 1
- CRHFOYCJGVJPLE-AVGNSLFASA-N Tyr-Gln-Asn Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O CRHFOYCJGVJPLE-AVGNSLFASA-N 0.000 description 1
- QUILOGWWLXMSAT-IHRRRGAJSA-N Tyr-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O QUILOGWWLXMSAT-IHRRRGAJSA-N 0.000 description 1
- LOOCQRRBKZTPKO-AVGNSLFASA-N Tyr-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 LOOCQRRBKZTPKO-AVGNSLFASA-N 0.000 description 1
- HKYTWJOWZTWBQB-AVGNSLFASA-N Tyr-Glu-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HKYTWJOWZTWBQB-AVGNSLFASA-N 0.000 description 1
- NJLQMKZSXYQRTO-FHWLQOOXSA-N Tyr-Glu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NJLQMKZSXYQRTO-FHWLQOOXSA-N 0.000 description 1
- HIINQLBHPIQYHN-JTQLQIEISA-N Tyr-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HIINQLBHPIQYHN-JTQLQIEISA-N 0.000 description 1
- NOOMDULIORCDNF-IRXDYDNUSA-N Tyr-Gly-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NOOMDULIORCDNF-IRXDYDNUSA-N 0.000 description 1
- CTDPLKMBVALCGN-JSGCOSHPSA-N Tyr-Gly-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O CTDPLKMBVALCGN-JSGCOSHPSA-N 0.000 description 1
- WVGKPKDWYQXWLU-BZSNNMDCSA-N Tyr-His-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCCN)C(=O)O)N)O WVGKPKDWYQXWLU-BZSNNMDCSA-N 0.000 description 1
- KIJLSRYAUGGZIN-CFMVVWHZSA-N Tyr-Ile-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KIJLSRYAUGGZIN-CFMVVWHZSA-N 0.000 description 1
- AXWBYOVVDRBOGU-SIUGBPQLSA-N Tyr-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N AXWBYOVVDRBOGU-SIUGBPQLSA-N 0.000 description 1
- WSFXJLFSJSXGMQ-MGHWNKPDSA-N Tyr-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N WSFXJLFSJSXGMQ-MGHWNKPDSA-N 0.000 description 1
- OHOVFPKXPZODHS-SJWGOKEGSA-N Tyr-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OHOVFPKXPZODHS-SJWGOKEGSA-N 0.000 description 1
- KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 1
- DWAMXBFJNZIHMC-KBPBESRZSA-N Tyr-Leu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O DWAMXBFJNZIHMC-KBPBESRZSA-N 0.000 description 1
- DAOREBHZAKCOEN-ULQDDVLXSA-N Tyr-Leu-Met Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O DAOREBHZAKCOEN-ULQDDVLXSA-N 0.000 description 1
- BYAKMYBZADCNMN-JYJNAYRXSA-N Tyr-Lys-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O BYAKMYBZADCNMN-JYJNAYRXSA-N 0.000 description 1
- VTCKHZJKWQENKX-KBPBESRZSA-N Tyr-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O VTCKHZJKWQENKX-KBPBESRZSA-N 0.000 description 1
- SBLZVFCEOCWRLS-BPNCWPANSA-N Tyr-Met-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)N SBLZVFCEOCWRLS-BPNCWPANSA-N 0.000 description 1
- KZOZXAYPVKKDIO-UFYCRDLUSA-N Tyr-Met-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 KZOZXAYPVKKDIO-UFYCRDLUSA-N 0.000 description 1
- BGFCXQXETBDEHP-BZSNNMDCSA-N Tyr-Phe-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O BGFCXQXETBDEHP-BZSNNMDCSA-N 0.000 description 1
- WURLIFOWSMBUAR-SLFFLAALSA-N Tyr-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O WURLIFOWSMBUAR-SLFFLAALSA-N 0.000 description 1
- PLXQRTXVLZUNMU-RNXOBYDBSA-N Tyr-Phe-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)N PLXQRTXVLZUNMU-RNXOBYDBSA-N 0.000 description 1
- ZPFLBLFITJCBTP-QWRGUYRKSA-N Tyr-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O ZPFLBLFITJCBTP-QWRGUYRKSA-N 0.000 description 1
- MQGGXGKQSVEQHR-KKUMJFAQSA-N Tyr-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MQGGXGKQSVEQHR-KKUMJFAQSA-N 0.000 description 1
- HRHYJNLMIJWGLF-BZSNNMDCSA-N Tyr-Ser-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 HRHYJNLMIJWGLF-BZSNNMDCSA-N 0.000 description 1
- UMSZZGTXGKHTFJ-SRVKXCTJSA-N Tyr-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 UMSZZGTXGKHTFJ-SRVKXCTJSA-N 0.000 description 1
- MDXLPNRXCFOBTL-BZSNNMDCSA-N Tyr-Ser-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MDXLPNRXCFOBTL-BZSNNMDCSA-N 0.000 description 1
- LDKDSFQSEUOCOO-RPTUDFQQSA-N Tyr-Thr-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LDKDSFQSEUOCOO-RPTUDFQQSA-N 0.000 description 1
- AOIZTZRWMSPPAY-KAOXEZKKSA-N Tyr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)O AOIZTZRWMSPPAY-KAOXEZKKSA-N 0.000 description 1
- KLQPIEVIKOQRAW-IZPVPAKOSA-N Tyr-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O KLQPIEVIKOQRAW-IZPVPAKOSA-N 0.000 description 1
- PQPWEALFTLKSEB-DZKIICNBSA-N Tyr-Val-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PQPWEALFTLKSEB-DZKIICNBSA-N 0.000 description 1
- DJIJBQYBDKGDIS-JYJNAYRXSA-N Tyr-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(C)C)C(O)=O DJIJBQYBDKGDIS-JYJNAYRXSA-N 0.000 description 1
- 108010064997 VPY tripeptide Proteins 0.000 description 1
- IZFVRRYRMQFVGX-NRPADANISA-N Val-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N IZFVRRYRMQFVGX-NRPADANISA-N 0.000 description 1
- WGHVMKFREWGCGR-SRVKXCTJSA-N Val-Arg-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WGHVMKFREWGCGR-SRVKXCTJSA-N 0.000 description 1
- PFNZJEPSCBAVGX-CYDGBPFRSA-N Val-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N PFNZJEPSCBAVGX-CYDGBPFRSA-N 0.000 description 1
- VMRFIKXKOFNMHW-GUBZILKMSA-N Val-Arg-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N VMRFIKXKOFNMHW-GUBZILKMSA-N 0.000 description 1
- UDLYXGYWTVOIKU-QXEWZRGKSA-N Val-Asn-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UDLYXGYWTVOIKU-QXEWZRGKSA-N 0.000 description 1
- IDKGBVZGNTYYCC-QXEWZRGKSA-N Val-Asn-Pro Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(O)=O IDKGBVZGNTYYCC-QXEWZRGKSA-N 0.000 description 1
- JLFKWDAZBRYCGX-ZKWXMUAHSA-N Val-Asn-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N JLFKWDAZBRYCGX-ZKWXMUAHSA-N 0.000 description 1
- PVPAOIGJYHVWBT-KKHAAJSZSA-N Val-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N)O PVPAOIGJYHVWBT-KKHAAJSZSA-N 0.000 description 1
- KXUKIBHIVRYOIP-ZKWXMUAHSA-N Val-Asp-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N KXUKIBHIVRYOIP-ZKWXMUAHSA-N 0.000 description 1
- OVLIFGQSBSNGHY-KKHAAJSZSA-N Val-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N)O OVLIFGQSBSNGHY-KKHAAJSZSA-N 0.000 description 1
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- IRLYZKKNBFPQBW-XGEHTFHBSA-N Val-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N)O IRLYZKKNBFPQBW-XGEHTFHBSA-N 0.000 description 1
- HURRXSNHCCSJHA-AUTRQRHGSA-N Val-Gln-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HURRXSNHCCSJHA-AUTRQRHGSA-N 0.000 description 1
- AAOPYWQQBXHINJ-DZKIICNBSA-N Val-Gln-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N AAOPYWQQBXHINJ-DZKIICNBSA-N 0.000 description 1
- XGJLNBNZNMVJRS-NRPADANISA-N Val-Glu-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O XGJLNBNZNMVJRS-NRPADANISA-N 0.000 description 1
- CVIXTAITYJQMPE-LAEOZQHASA-N Val-Glu-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CVIXTAITYJQMPE-LAEOZQHASA-N 0.000 description 1
- PMXBARDFIAPBGK-DZKIICNBSA-N Val-Glu-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PMXBARDFIAPBGK-DZKIICNBSA-N 0.000 description 1
- JTWIMNMUYLQNPI-WPRPVWTQSA-N Val-Gly-Arg Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N JTWIMNMUYLQNPI-WPRPVWTQSA-N 0.000 description 1
- WFENBJPLZMPVAX-XVKPBYJWSA-N Val-Gly-Glu Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O WFENBJPLZMPVAX-XVKPBYJWSA-N 0.000 description 1
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 1
- PMDOQZFYGWZSTK-LSJOCFKGSA-N Val-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)C(C)C PMDOQZFYGWZSTK-LSJOCFKGSA-N 0.000 description 1
- MDYSKHBSPXUOPV-JSGCOSHPSA-N Val-Gly-Phe Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N MDYSKHBSPXUOPV-JSGCOSHPSA-N 0.000 description 1
- YTPLVNUZZOBFFC-SCZZXKLOSA-N Val-Gly-Pro Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N1CCC[C@@H]1C(O)=O YTPLVNUZZOBFFC-SCZZXKLOSA-N 0.000 description 1
- KZKMBGXCNLPYKD-YEPSODPASA-N Val-Gly-Thr Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O KZKMBGXCNLPYKD-YEPSODPASA-N 0.000 description 1
- BVWPHWLFGRCECJ-JSGCOSHPSA-N Val-Gly-Tyr Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N BVWPHWLFGRCECJ-JSGCOSHPSA-N 0.000 description 1
- PTFPUAXGIKTVNN-ONGXEEELSA-N Val-His-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)NCC(=O)O)N PTFPUAXGIKTVNN-ONGXEEELSA-N 0.000 description 1
- DLMNFMXSNGTSNJ-PYJNHQTQSA-N Val-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)N DLMNFMXSNGTSNJ-PYJNHQTQSA-N 0.000 description 1
- BZMIYHIJVVJPCK-QSFUFRPTSA-N Val-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N BZMIYHIJVVJPCK-QSFUFRPTSA-N 0.000 description 1
- FTKXYXACXYOHND-XUXIUFHCSA-N Val-Ile-Leu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O FTKXYXACXYOHND-XUXIUFHCSA-N 0.000 description 1
- OVBMCNDKCWAXMZ-NAKRPEOUSA-N Val-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](C(C)C)N OVBMCNDKCWAXMZ-NAKRPEOUSA-N 0.000 description 1
- APQIVBCUIUDSMB-OSUNSFLBSA-N Val-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N APQIVBCUIUDSMB-OSUNSFLBSA-N 0.000 description 1
- FEXILLGKGGTLRI-NHCYSSNCSA-N Val-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N FEXILLGKGGTLRI-NHCYSSNCSA-N 0.000 description 1
- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 1
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 1
- 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 1
- ZRSZTKTVPNSUNA-IHRRRGAJSA-N Val-Lys-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(O)=O ZRSZTKTVPNSUNA-IHRRRGAJSA-N 0.000 description 1
- WMRWZYSRQUORHJ-YDHLFZDLSA-N Val-Phe-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)O)N WMRWZYSRQUORHJ-YDHLFZDLSA-N 0.000 description 1
- YLRAFVVWZRSZQC-DZKIICNBSA-N Val-Phe-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N YLRAFVVWZRSZQC-DZKIICNBSA-N 0.000 description 1
- HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 1
- XBJKAZATRJBDCU-GUBZILKMSA-N Val-Pro-Ala Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XBJKAZATRJBDCU-GUBZILKMSA-N 0.000 description 1
- RYQUMYBMOJYYDK-NHCYSSNCSA-N Val-Pro-Glu Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RYQUMYBMOJYYDK-NHCYSSNCSA-N 0.000 description 1
- HWNYVQMOLCYHEA-IHRRRGAJSA-N Val-Ser-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N HWNYVQMOLCYHEA-IHRRRGAJSA-N 0.000 description 1
- CEKSLIVSNNGOKH-KZVJFYERSA-N Val-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](C(C)C)N)O CEKSLIVSNNGOKH-KZVJFYERSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- DLRZGNXCXUGIDG-KKHAAJSZSA-N Val-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O DLRZGNXCXUGIDG-KKHAAJSZSA-N 0.000 description 1
- UVHFONIHVHLDDQ-IFFSRLJSSA-N Val-Thr-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O UVHFONIHVHLDDQ-IFFSRLJSSA-N 0.000 description 1
- PDDJTOSAVNRJRH-UNQGMJICSA-N Val-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](C(C)C)N)O PDDJTOSAVNRJRH-UNQGMJICSA-N 0.000 description 1
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 1
- SUGRIIAOLCDLBD-ZOBUZTSGSA-N Val-Trp-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(=O)O)C(=O)O)N SUGRIIAOLCDLBD-ZOBUZTSGSA-N 0.000 description 1
- PFMSJVIPEZMKSC-DZKIICNBSA-N Val-Tyr-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PFMSJVIPEZMKSC-DZKIICNBSA-N 0.000 description 1
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- OWNKJJAVEHMKCW-XVFCMESISA-N [(2r,3s,4r,5r)-4-amino-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate Chemical compound N[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 OWNKJJAVEHMKCW-XVFCMESISA-N 0.000 description 1
- KHIXTHDBCAQXRC-JXOAFFINSA-N [(2r,3s,4r,5r)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 KHIXTHDBCAQXRC-JXOAFFINSA-N 0.000 description 1
- KPUOHXMVCZBWQC-JXOAFFINSA-N [(2r,3s,4r,5r)-5-[4-amino-5-(hydroxymethyl)-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 KPUOHXMVCZBWQC-JXOAFFINSA-N 0.000 description 1
- JVCCCMWZAFGSPD-JXOAFFINSA-N [(2r,3s,4r,5r)-5-[4-amino-5-(hydroxymethyl)-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 JVCCCMWZAFGSPD-JXOAFFINSA-N 0.000 description 1
- YIJVOACVHQZMKI-JXOAFFINSA-N [[(2r,3s,4r,5r)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 YIJVOACVHQZMKI-JXOAFFINSA-N 0.000 description 1
- NAOOSVVUTFPWHI-JXOAFFINSA-N [[(2r,3s,4r,5r)-5-[4-amino-5-(hydroxymethyl)-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 NAOOSVVUTFPWHI-JXOAFFINSA-N 0.000 description 1
- ASJWEHCPLGMOJE-LJMGSBPFSA-N ac1l3rvh Chemical class N1C(=O)NC(=O)[C@@]2(C)[C@@]3(C)C(=O)NC(=O)N[C@H]3[C@H]21 ASJWEHCPLGMOJE-LJMGSBPFSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000013006 addition curing Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010078114 alanyl-tryptophyl-alanine Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 108010070783 alanyltyrosine Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000005005 aminopyrimidines Chemical class 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 235000021015 bananas Nutrition 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000003508 chemical denaturation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- MSBXTPRURXJCPF-DQWIULQBSA-N cucurbit[6]uril Chemical compound N1([C@@H]2[C@@H]3N(C1=O)CN1[C@@H]4[C@@H]5N(C1=O)CN1[C@@H]6[C@@H]7N(C1=O)CN1[C@@H]8[C@@H]9N(C1=O)CN([C@H]1N(C%10=O)CN9C(=O)N8CN7C(=O)N6CN5C(=O)N4CN3C(=O)N2C2)C3=O)CN4C(=O)N5[C@@H]6[C@H]4N2C(=O)N6CN%10[C@H]1N3C5 MSBXTPRURXJCPF-DQWIULQBSA-N 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- 108010016616 cysteinylglycine Proteins 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000009144 enzymatic modification Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003617 erythrocyte membrane Anatomy 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 108010090037 glycyl-alanyl-isoleucine Proteins 0.000 description 1
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 1
- 108010028188 glycyl-histidyl-serine Proteins 0.000 description 1
- 108010043293 glycyl-prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010048994 glycyl-tyrosyl-alanine Proteins 0.000 description 1
- 108010045126 glycyl-tyrosyl-glycine Proteins 0.000 description 1
- 108010059898 glycyl-tyrosyl-lysine Proteins 0.000 description 1
- 108010020688 glycylhistidine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000002847 impedance measurement Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229920000592 inorganic polymer Polymers 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000011810 insulating material Substances 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 108010027338 isoleucylcysteine Proteins 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
- 238000002372 labelling Methods 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 1
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 108010091871 leucylmethionine Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000013554 lipid monolayer Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108010016686 methionyl-alanyl-serine Proteins 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000004377 microelectronic Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002052 molecular layer Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 108010074082 phenylalanyl-alanyl-lysine Proteins 0.000 description 1
- 108010064486 phenylalanyl-leucyl-valine Proteins 0.000 description 1
- 108010024654 phenylalanyl-prolyl-alanine Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 108010025826 prolyl-leucyl-arginine Proteins 0.000 description 1
- 108010020432 prolyl-prolylisoleucine Proteins 0.000 description 1
- 108010004914 prolylarginine Proteins 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 102220198313 rs1057519973 Human genes 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 101150072534 sbcB gene Proteins 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000018448 secretion by cell Effects 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 201000003708 skin melanoma Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 229920003046 tetrablock copolymer Polymers 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 108010033670 threonyl-aspartyl-tyrosine Proteins 0.000 description 1
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 229920000428 triblock copolymer Polymers 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 108010058119 tryptophyl-glycyl-glycine Proteins 0.000 description 1
- 108010038745 tryptophylglycine Proteins 0.000 description 1
- 230000005641 tunneling Effects 0.000 description 1
- 108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 108010003885 valyl-prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 101150097442 xthA gene Proteins 0.000 description 1
- MLBMCAGVSIMKNT-UHFFFAOYSA-N β-cds Chemical compound O1C(C(C2OS(O)(=O)=O)OS(O)(=O)=O)C(COS(O)(=O)=O)OC2OC(C(C2OS(O)(=O)=O)OS(O)(=O)=O)C(COS(O)(=O)=O)OC2OC(C(C2OS(O)(=O)=O)OS(O)(=O)=O)C(COS(O)(=O)=O)OC2OC(C(C2OS(O)(=O)=O)OS(O)(=O)=O)C(COS(O)(=O)=O)OC2OC(C(OS(O)(=O)=O)C2OS(O)(=O)=O)C(COS(=O)(=O)O)OC2OC(C(C2OS(O)(=O)=O)OS(O)(=O)=O)C(COS(O)(=O)=O)OC2OC2C(OS(O)(=O)=O)C(OS(O)(=O)=O)C1OC2COS(O)(=O)=O MLBMCAGVSIMKNT-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Electrochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明涉及胞溶素的突变体形式。本发明还涉及使用胞溶素来表征分析物。
Description
本申请为2013年03月15日申请的申请号为2013800305272的发明名称为突变胞溶素孔的分案申请。
技术领域
本发明涉及的胞溶素(lysenin)的突变体形式。本发明还涉及使用胞溶素的突变体形式进行的分析物表征。
背景技术
纳米孔感测是一种依靠对分析物分子和受体之间的单个结合或相互作用事件的观察进行检测的方法。纳米孔传感器可以通过在绝缘膜中放置纳米尺寸的单个孔并在分析物分子存在下测量在电压驱动下穿过孔进行离子传输而建立。分析物的相似性(identity)是通过其独特的电流信号而揭示，特别是电流模块(current block)的持续时间和程度以及电流水平的变化。
目前需要能在广泛范围内应用的快速且廉价的核酸(例如DNA或RNA)测序技术。现有的技术缓慢且昂贵，主要是因为它们依赖于扩增技术来生产大体积核酸并需要大量专门的荧光化学物质进行信号检测。纳米孔感测具有能够通过减少所需的核苷酸和试剂的量来提供快速且廉价的核酸测序的潜力。
使用纳米孔感测测序核酸的两个主要要素为(1)控制核酸穿过孔的运动和(2)随着核酸聚合物运动穿过所述孔识别核苷酸。在过去，为了实现对核苷酸的识别，使核酸穿过溶血素的突变体。这提供的电流信号经证明具有序列依赖性。其还证明了，当使用溶血素孔时，需要大量的核苷酸以使观察到的电流增加，这使得对所观察的电流与多核苷酸之间的直接相关性受到质疑。
虽然用于核苷酸识别的电流范围已通过溶血素孔的突变得到改进，但是如果核苷酸之间的电流差异能够被进一步改善的话，测序系统将具有更高的性能。此外，已观察到，当核酸移动穿过孔时，一些电流状态显示较高的差异。还表明，一些溶血素孔突变体比其他溶血素孔突变体具有更高的差异。虽然这些状态的差异可能包含序列的特异性信息，但是希望的是能产生具有较低差异的孔以简化系统。还希望减少使观察到的电流增加的核苷酸的数量。
胞溶素(也被称为efL1)是一种来自蚯蚓赤子爱胜蚓(Eisenia fetida)的体腔液的经纯化的孔形成毒素(pore-forming toxin)。其特异性结合到鞘磷脂，从而抑制胞溶素诱导的溶血作用(Yamaji等人，J.Biol.Chem.1998；273(9):5300-6)。胞溶素的晶体结构在De Colbis等人，Structure,2012；20:1498–1507中有公开。
发明内容
出人意料地，本发明人识别出了胞溶素单体内的一个区域，该区域可被修饰为用以改变该单体和多核苷酸之间的相互作用。该区域对应于SEQ ID NO:2的约44位点到约126位点。本发明涉及这样的突变体单体：在其中对所述识别出的区域进行一个或多个修饰以改善所述突变体单体与多核苷酸相互作用的能力。出人意料地，本发明人还证实了，含有该新的突变体单体的孔具有增强的与多核苷酸相互作用的能力，并因此显示出提高的用以评估多核苷酸特征如序列特征的性能。出人意料地，所述突变体孔显示出提高的核苷酸识别能力。特别是，出人意料地，所述突变体孔显示出增加的电流范围，这使得更容易区分不同核苷酸，并且显示出减少的状态变化，这提高了信噪比。此外，减少了在多核苷酸移动穿过孔时使电流增加的核苷酸的数目。这使得更容易确定多核苷酸移动穿过所述孔时所观察到的电流与所述多核苷酸之间的直接关系。
因此，本发明提供了一种包含SEQ ID NO:2中所示序列的变体的突变体胞溶素单体，其中所述单体能够形成孔并且其中所述变体在SEQ ID NO:2的约44位点到约126位点的区域内包含一个或多个修饰，所述修饰能改变所述单体与多核苷酸相互作用的能力。
本发明还提供：
-一种构造，包含两个或多个共价连接的源自胞溶素的单体，其中所述单体中的至少一个为本发明的突变体胞溶素单体；
-一种多核苷酸，其编码本发明的突变体胞溶素单体或本发明的基因融合的构造(genetically fused construct)；
-一个源自胞溶素的同源寡聚孔，包含足够数目的本发明的突变体胞溶素单体；
-一个源自胞溶素的异源寡聚孔，包含至少一个本发明的突变体胞溶素单体；
-一种孔，包含至少一个本发明的构造；
-一种表征目标分析物的方法，包括：(a)使目标多核苷酸与本发明的孔接触，使得目标多核苷酸移动穿过所述孔；和(b)在分析物相对于所述孔移动时获取一个或多个测量值，其中所述测量值表示所述目标分析物的一个或多个特征并由此表征所述目标分析物；
-一种形成表征目标多核苷酸用传感器的方法，包括在本发明的孔和多核苷酸结合蛋白之间形成复合体，并由此形成用于表征目标多核苷酸的传感器；
-一种用于表征目标多核苷酸的传感器，包括在本发明的孔和多核苷酸结合蛋白之间的复合体；
-本发明的孔在表征目标分析物中的应用；
-用于表征目标多核苷酸的试剂盒，包括(a)本发明的孔和(b)多核苷酸结合蛋白；
-一种用于表征样本中目标多核苷酸的设备，包括(a)多个本发明的孔和(b)多个多核苷酸结合蛋白；
-一种提高含SEQ ID NO:2中所示序列的胞溶素单体用于表征多核苷酸的能力的方法，包括在SEQ ID NO:2的约44位点到约126位点的区域内进行一个或多个修饰，所述修饰会改变所述单体与多核苷酸相互作用的能力并且不影响所述单体用于形成孔的能力；
-一种制备本发明的构造的方法，包括将至少一个本发明的突变体胞溶素单体共价连接到一个或多个源自胞溶素的单体；和
-一种形成本发明孔的方法，包括使至少一个本发明突变体单体或至少一个本发明构造与足够数目的本发明单体、本发明构造或源自胞溶素的单体进行寡聚用以形成孔。
附图说明
图1显示了使用解旋酶(标记为A)控制DNA移动穿过胞溶素纳米孔(标记为B)的示例图。1)将单链DNA底物与含有胆固醇标签(标记为D)的退火引物添加到双分子层(标记为C)的顺侧(标记为X)。所述胆固醇标签结合到所述双分子层，使所述底物富集在所述双分子层表面处。2)被加成到顺侧隔室(compartment)的解旋酶结合到所述DNA。在二价金属离子和NTP底物的存在下，所述解旋酶沿着所述DNA运动(灰色箭头)。3)在施加的电压下，纳米孔通过DNA上的前导区部分捕获所述DNA底物。在施加的电势的力的作用下，所述DNA被牵拉穿过所述孔直到结合在所述DNA上的解旋酶与所述孔的顶部接触，防止进一步的不受控的DNA移位。在该过程中，双链DNA部分(例如引物)被去除。所述解旋酶沿着所述DNA以3’到5’的方向运动并逆着所施加的电场将螺旋状(threaded)DNA(DNA的运动方向用黑色箭头示出)牵拉出所述孔。4)所述解旋酶将所述DNA牵拉出所述纳米孔，从而将所述DNA供回到所述顺式隔室。穿过所述纳米孔的DNA的最后部分为所述5’-前导区。5)当所述解旋酶将所述DNA移出所述纳米孔后，所述解旋酶被释放回所述顺侧隔室中。替代地，如果所述DNA 3’端被捕获，则所述DNA将在3’-5’解旋酶的控制下从顺侧移动穿过所述孔到达反侧(标记为Y)，从而最终在双分子层的反侧上离开。
图2显示了实施例1,2,3,4,5和6中所使用的DNA底物设计。所述DNA底物由PhiX(SEQ ID NO:13,标记为A)中单链DNA的一400碱基部分与一50T 5’-前导区(由链A虚线区域表示)组成。在50T前导区后退火到该链的是含有3’胆固醇标签(标记为C)的引物(标记为B)，以使使DNA富集在所述双分子层的表面上并由此提高捕获效率。
图3显示了插入到DPhPC双分子层中的野生型胞溶素孔的电流轨迹(对于A和B，y轴＝电流(pA)，x轴＝时间(min))。A)显示了在不存在DNA和解旋酶的情况下在+120mV下观察到约+280pA的稳定开孔(open-pore)电流(625mM KCl,100mM Hepes(4-羟乙基哌嗪乙磺酸),pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2,野生型胞溶素(SEQID NO:2))。B)显示了在添加DNA、解旋酶和ATP的情况下(0.3nM400mer DNA(SEQ ID NO:13和14),Hel308 Mbu,(100nM,SEQ ID NO:15),1mM ATP)，没有明显的DNA捕获，并且没有解旋酶控制的DNA移动穿过所述纳米孔。
图4显示了Hel308 Mbu(SEQ ID NO:15)能够以受控的方式移动DNA穿过胞溶素纳米孔(胞溶素-E84D/E85K,具有突变E84D/E85K的SEQ ID NO:2)，从而随着所述DNA移动穿过所述纳米孔电流产生逐步的变化。A)显示了DNA捕获和Hel308 Mbu控制的400merDNA运动的示例性电流轨迹(y轴＝电流(pA),x轴＝时间(min))，从～400pA的开孔水平观察到较低的在～200pA下的电流模块(180mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾,0.3nM 400mer DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15),1mM ATP,10mM MgCl2,胞溶素-E84D/E85K(具有突变E84D/E85K的SEQ ID NO:2))。图中星号表示解旋酶控制的DNA移动。在施加的电势下，结合有解旋酶的DNA被胞溶素纳米孔捕获。这得到从开孔水平(～400pA)到DNA水平(～220pA)的电流模块。B)显示了上图轨迹中所述解旋酶控制的DNA移动的放大图(y轴＝电流(pA),x轴＝时间(min))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图5显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E92N/E94N/E97N/D121N/D126N,具有突变E92N/E94N/E97N/D121N/D126N的SEQ IDNO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308Mbu控制400mer DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(min))(120mV,625mMKCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾,0.3nM 400mer DNA(SEQID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15),1mM ATP,10mM MgCl2,胞溶素-E92N/E94N/E97N/D121N/D126N(具有突变E92N/E94N/E97N/D121N/D126N的SEQ ID NO:2))。在施加的电势下，DNA被胞溶素纳米孔捕获。该胞溶素突变体显示出高水平的DNA捕获vs.WT胞溶素。在所述孔中被捕获的DNA产生从开孔水平(～280pA)到DNA水平(～110pA)的电流模块。结合有解旋酶的DNA在所述酶移动DNA穿过所述孔时显示出逐步变化的电流。将解旋酶控制的DNA移动由星号标出。B)为上图轨迹中典型的解旋酶控制的DNA移动中的一个的放大图(y轴＝电流(pA),x轴＝时间(min))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图6显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308 Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(min))(180mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾,0.6nM400mer DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15),1mM ATP,10mMMgCl2,胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A(具有突变E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2))。在施加的电势下，DNA被胞溶素纳米孔捕获。该胞溶素突变体显示出高水平的DNA捕获vs.WT胞溶素。在所述孔中被捕获的DNA产生从开孔水平(～390pA)到DNA水平(～200pA)的电流模块。结合有解旋酶的DNA显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。将解旋酶控制的DNA移动由星号标出。B)为上图轨迹中典型的解旋酶控制DNA移动中的一个的放大图(y轴＝电流(pA),x轴＝时间(min))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图7显示出Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E76S/E84Q/E85K/E92Q/E97S/D126G/E167A,具有突变E76S/E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(s))(+180mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.6nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15),胞溶素-E76S/E84Q/E85K/E92Q/E97S/D126G/E167A,具有突变E76S/E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2))。B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图8显示出Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E50S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E50S的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308 Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(s))(+120mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.3nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15)，胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E50S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E50S的SEQ ID NO:2))。B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图9显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E71S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E71S的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(min))(+180mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.3nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15),胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E71S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E71S的SEQ ID NO:2).B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图10显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E128S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E128S的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(s))(+180mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.6nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15)，胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/E128S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/E128S的SEQ ID NO:2)。B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图11显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/D68S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/D68S的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(min))(+120mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.3nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15)，胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/D68S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/D68S的SEQ ID NO:2)。B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
图12显示了Hel308 Mbu(SEQ ID NO:15)能以受控方式移动DNA穿过胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/D121S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/D121S的SEQ ID NO:2)，从而在随着DNA移动穿过所述纳米孔电流产生逐步变化。A)显示了典型的Hel308 Mbu控制的DNA移动的示例电流轨迹(y轴＝电流(pA),x轴＝时间(s))(+120mV,625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,1mM ATP,10mM MgCl2,0.6nM DNA(SEQ ID NO:13和14),100nM Hel308 Mbu(SEQ ID NO:15)，胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A/D121S,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A/D121S的SEQ ID NO:2)。B)显示了上图轨迹中解旋酶控制的DNA移动的一放大图(y轴＝电流(pA),x轴＝时间(s))。所述DNA水平显示出随着所述酶移动DNA穿过所述孔电流是逐步变化的。
序列表说明
SEQ ID NO:1示出了编码胞溶素单体的多核苷酸序列。
SEQ ID NO:2示出了胞溶素单体的氨基酸序列。
SEQ ID NO:3示出了编码Phi29 DNA聚合酶的多核苷酸序列。
SEQ ID NO:4示出了Phi29 DNA聚合酶的氨基酸序列。
SEQ ID NO:5示出了源自大肠杆菌(E.coli)的sbcB基因的密码子优化的多核苷酸序列。其编码大肠杆菌的核酸外切酶I(EcoExo I)。
SEQ ID NO:6示出了大肠杆菌的核酸外切酶I(EcoExo I)的氨基酸序列。
SEQ ID NO:7示出了源自大肠杆菌的xthA基因的密码子优化的多核苷酸序列。其编码大肠杆菌的核酸外切酶III。
SEQ ID NO:8示出了大肠杆菌的核酸外切酶III的氨基酸序列。该酶从双链DNA(dsDNA)中的一条链沿3’–5’方向执行对5’单磷酸核苷的分配酶解(distributivedigestion)。酶在链上的引发需要约4个核苷酸的5’突出。
SEQ ID NO:9示出了源自极端嗜热菌(T.thermophilus)的recJ基因的密码子优化的多核苷酸序列。其编码极端嗜热菌的RecJ酶(TthRecJ-cd)。
SEQ ID NO:10示出了极端嗜热菌的RecJ酶(TthRecJ-cd)的氨基酸序列。该酶从单链DNA沿5’–3’方向执行对5’单磷酸核苷的进行性酶解(processive digestion)。酶在链上的引发需要至少4个核苷酸。
SEQ ID NO:11示出了源自噬菌体λ核酸外切酶(bacteriophage lambda exo)(redX)基因的密码子优化的多核苷酸序列。其编码噬菌体λ核酸外切酶。
SEQ ID NO:12示出了噬菌体λ核酸外切酶的氨基酸序列。该序列是组装成三聚体的三个相同亚基中的一个。所述酶从双链DNA中的一条链沿5’-3’方向执行对核苷酸的高进行性酶解(http://www.neb.com/nebecomm/products/productM0262.asp)。酶在链上的引发优先需要约4个具有5’磷酸的核苷酸的5’突出。
SEQ ID NO:13和14示出了在实施例1,2,3,4,5和6中使用的单链DNA的多核苷酸序列。SEQ ID NO:14具有3’-胆固醇标签。
SEQ ID NO:15示出了Hel308 Mbu的氨基酸序列。
SEQ ID NO:16示出了胞溶素相关蛋白质(LRP)1的氨基酸序列。
SEQ ID NO:17示出了胞溶素相关蛋白质(LRP)1的氨基酸序列。
SEQ ID NO:18示出了胞溶素相关蛋白质(LRP)1的氨基酸序列。
SEQ ID NO:19示出了抗癌晶体蛋白-2(parasporin-2)的活性变体的氨基酸序列。该全长蛋白在其氨基和羧基末端裂开从而形成能够形成孔的活性变体。
具体实施方式
应理解的是，所公开的产品和方法的不同应用可以根据本领域的具体需求进行调整。还应理解的是，本文中使用的术语仅仅是为了描述本发明的具体实施方案，不意欲进行限制。
另外，如在本说明书和所附权利要求书中使用的，单数形式的“一个”、“所述”包括复数指代物，除非文中另有明确说明。因此，例如，涉及“一个突变体单体”时包括“多个突变体单体”，涉及“一个取代”时包括两个或多个这样的取代，涉及“一个孔”时包括两个或多个这样的孔，涉及“一个多核苷酸”时包括两个或多个这样的多核苷酸，等。
所有在本文中引用的出版物、专利和专利申请，无论在前文或后文，均以全文引用的方式纳入本文中。
突变体胞溶素单体
本发明提供了突变体胞溶素单体。所述突变体胞溶素单体可用于形成本发明的孔。突变体胞溶素单体为其序列由野生型胞溶素单体的序列(即SEQ ID NO:2)变化而来且在本发明其他单体或者胞溶素的或源自胞溶素的其他单体存在下保持有形成孔的能力的单体。用于确定突变体单体形成孔的能力的方法是本领域公知的且将在下文更详细论述。例如，所述突变体单体形成孔的能力可按实施例1中所述确定。
所述突变体单体具有改变的与多核苷酸相互作用的能力。因此，含有一个或多个突变体单体的孔具有提高的核苷酸读取性能，例如显示出(1)提高的多核苷酸捕获和(2)提高的多核苷酸识别或区分能力。特别地，由所述突变体单体构造的孔能比野生型的能更容易地捕获核苷酸和多核苷酸。此外，由所述突变体单体构造的孔显示出增加的电流范围，这使得更容易区分不同的核苷酸，且显示出降低的状态变化，这提高了信噪比。此外，在多核苷酸移动穿过由所述突变体构造的孔时使电流增加的核苷酸的数目减少了。这使得更容易确定多核苷酸移动穿过所述孔时所观察到的电流与所述多核苷酸之间的直接关系。所述突变体的提高的核苷酸读取性能通过五种主要机制实现，即可通过改变下述而实现：
·空间位阻(teric)(增加或减小氨基酸残基的尺寸)；
·电荷(例如引入或去除–ve电荷和/或引入或去除+ve电荷)；
·氢键合(例如引入可将氢键合至碱基对的氨基酸)；
·π-堆积(例如引入通过离域电子π体系而相互作用的氨基酸)；和/或
.改变所述孔的结构(例如引入能增加桶状结构或通道的尺寸的氨基酸)。
上述五种机制中的任何一种或多种是本发明突变体单体形成的孔的性能得以提高的原因。例如，含有本发明突变体单体的孔可由于改变的空间位阻、改变的氢键合和改变的结构而显示出提高的核苷酸读取性能。
本发明突变体单体含有SEQ ID NO:2中所示序列的变体。SEQ ID NO:2为胞溶素单体的野生型序列。SEQ ID NO:2的变体为具有由SEQ ID NO:2的氨基酸序列变化而来的氨基酸序列且保持有其形成孔的能力的多肽。
出人意料地，本发明人识别出了胞溶素单体内的一个区域，该区域可被修饰用以改变所述单体和多核苷酸之间的相互作用，例如当使用纳米孔通过含所述单体的孔感测表征所述多核苷酸时。所述区域为SEQ ID NO:2的约44位点到约126位点。通常至少该区域的一部分为胞溶素的跨膜区域。通常至少该区域的一部分为胞溶素的桶状结构或通道。通常至少该区域的一部分为胞溶素的内壁或内膜(lining)。
胞溶素的跨膜区域经鉴定为SEQ ID NO:2的44位点至67位点(De Colbis等人,Structure,2012；20:1498–1507)。
根据本发明，所述变体包含位于SEQ ID NO:2的从约44位点到约126位点的区域内的一个或多个修饰，所述修饰能改变所述单体或优选地所述区域与多核苷酸相互作用的能力。所述单体与多核苷酸之间的相互作用可被增加或减小。所述单体与多核苷酸之间的相互作用增加将例如有助于通过含所述突变体单体的孔对所述多核苷酸的捕获。所述区域与多核苷酸之间的相互作用减小将例如提高对所述多核苷酸的识别或区分。对所述多核苷酸的识别或区分可通过以下方式提高，通过减小含有突变体单体的孔的状态的变化(这将提高信噪比)和/或减小在所述多核苷酸移动穿过含有所述突变体单体的孔时使电流增加的所述多核苷酸中核苷酸的数目。
因此，本发明提供了含有SEQ ID NO:2中所示序列的变体的突变体胞溶素单体，其中所述单体能够形成孔并且其中所述变体包括SEQ ID NO:2的从约44位点到约126位点的一个或多个修饰，所述修饰能改变所述单体与多核苷酸相互作用的能力。
所述单体与多核苷酸相互作用的能力可使用本领域公知的方法确定。所述单体可与多核苷酸以任何方式相互作用，例如通过非共价相互作用如疏水性相互作用、氢键合、范德华力(Van der Waal’s force)、pi(π)-阳离子相互作用或静电力。例如，所述区域与多核苷酸结合的能力可使用常规结合试验测得。合适的试验包括但不限于，基于荧光的结合试验、核磁共振(NMR)、等温滴定量热法(ITC)和电子自旋共振(ESR)光谱法。替代地，包含一个或多个所述突变体单体的孔与多核苷酸相互作用的能力可使用上下文中所述的任一方法确定。优选的试验在实施例中有描述。
所述一个或多个修饰位于SEQ ID NO:2的约44位点到约126位点的区域中。所述一个或多个修饰优选位于以下区域中的任一个中：约40位点至约125位点、约50位点至约120位点、约60位点至约110位点和约70位点至约100位点。如果进行所述一个或多个修饰是为了提高对多核苷酸的捕获，则更优选在以下区域中的任一个中进行所述修饰：约44位点至约103位点、约68位点至约103位点、约84位点至约103位点、约44位点至约位点97、约68位点至约97位点或约84位点至约97位点。如果进行所述一个或多个修饰是为了提高对多核苷酸的识别或区分，则更优选在以下区域中的任一个中进行所述修饰：约44位点至约109位点、约44位点至约97位点或约48位点至约88位点。所述区域优选为SEQ ID NO:2的约44位点至约67位点。
如果所述一个或多个修饰是用于提高对多核苷酸的识别或区分，则优选在进行用于提高多核苷酸捕获的一个或多个修饰之外进行修饰。这使得由突变体单体形成的孔能有效捕获多核苷酸然后表征该多核苷酸，例如按如下所述评估其序列。
对蛋白质纳米孔的修饰——用以改变其与多核苷酸相互作用的能力，特别是提高其捕获和/或识别或区分多核苷酸的能力——在本领域中有充分的文献记载。例如，WO2010/034018和WO 2010/055307中公开了所述修饰。根据本发明，可对胞溶素单体进行类似的修饰。
可进行任何数目的修饰，如1,2,5,10,15,20,30个或更多的修饰。可进行任何修饰，只要能改变所述单体与多核苷酸相互作用的能力即可。合适的修饰包括，但不限于，氨基酸取代、氨基酸添加和氨基酸缺失。所述一个或多个修饰优选为一个或多个取代。这在下文有更详细论述。
所述一个或多个修饰优选地(a)改变所述单体的空间位阻效应或优选地改变所述区域的空间位阻效应，(b)改变所述单体的净电荷或优选地改变所述区域的净电荷，(c)改变所述单体与所述多核苷酸进行氢键合的能力，或优选地改变所述区域与所述多核苷酸进行氢键合的能力，(d)引入或去除通过离域电子π体系进行相互作用的化学基团，和/或(e)改变所述单体的结构，或优选地改变所述区域的结构。所述一个或多个修饰更优选地进行(a)至(e)的任意组合，例如(a)和(b)；(a)和(c)；(a)和(d)；(a)和(e)；(b)和(c)；(b)和(d)；(b)和(e)；(c)和(d)；(c)和(e)；(d)和(e),(a),(b)和(c)；(a),(b)和(d)；(a),(b)和(e)；(a),(c)和(d)；(a),(c)和(e)；(a),(d)和(e)；(b),(c)和(d)；(b),(c)和(e)；(b),(d)和(e)；(c),(d)和(e)；(a),(b),(c)and d)；(a),(b),(c)和(e)；(a),(b),(d)和(e)；(a),(c),(d)和(e)；(b),(c),(d)和(e)；(a),(b),(c)和(d)。
对于(a)，可增加或减小所述单体的空间位阻效应。根据本发明可以使用改变所述空间位阻效应的任何方法。引入大体积的(bulky)残基，例如苯丙氨酸(F)，色氨酸(W)，酪氨酸(Y)或组氨酸(H)，可增加所述单体的空间位阻。所述一个或多个修饰优选地是引入F、W、Y和H中的一个或多个。可以引入F、W、Y和H的任意组合。所述F、W、Y和H中的一个或多个可通过添加而引入。所述F、W、Y和H中的一个或多个优选地通过取代而引入。适于引入这类残基的位置在下面更详细地论述。
相反地，去除大体积的残基，例如苯丙氨酸(F)、色氨酸(W)、酪氨酸(Y)或组氨酸(H)，能减少所述单体的空间位阻。所述一个或多个修饰优选地是去除F、W、Y和H中的一个或多个。可以去除F、W、Y和H的任意组合。所述F、W、Y和H中的一个或多个可通过缺失而去除。所述F、W、Y和H中的一个或多个优选地通过用具有较小侧基的残基，例如例如丝氨酸(S)、苏氨酸(T)、丙氨酸(A)和缬氨酸(V)进行取代而去除。
对于(b)，可用任何方法改变所述净电荷。优选地增加或减少净正电荷。可用任何方式增加净正电荷。优选地，通过引入、优选通过取代一个或多个带正电的氨基酸和/或通过中和、优选通过取代一个或多个负电荷而增加净正电荷。
优选地，通过引入一个或多个带正电的氨基酸来增加净正电荷。所述一个或多个带正电的氨基酸可通过添加而引入。所述一个或多个带正电的氨基酸优选地通过取代而引入。带正电的氨基酸为带净正电荷的氨基酸。所述带正电的氨基酸可以是天然存在的或非天然存在的。所述带正电的氨基酸可以是合成的或经修饰的。例如，可以专门设计经修饰的带净正电荷的氨基酸而用于本发明中。对氨基酸的许多不同类型的修饰均是本领域中公知的。
优选的天然存在的带正电的氨基酸包括，但不限于，组氨酸(H)、赖氨酸(K)和精氨酸(R)。所述一个或多个修饰优选为引入H,K和R中的一个或多个。可以引入任意数目和任意组合的H,K和R。所述H,K和R中的一个或多个可通过添加而引入。所述H,K和R中的一个或多个优选地通过取代而引入。适于引入这类残基的位置在下文更详细论述。
添加或取代天然存在的氨基酸的方法是本领域公知的。例如，甲硫氨酸(M)可以用精氨酸(R)取代，通过在编码所述单体的多核苷酸相关位置通过用精氨酸的密码子(AGA)替换甲硫氨酸的密码子(ATG)而进行。然后所述多核苷酸可按如下所述进行表达。
添加或取代非天然存在的氨基酸的方法也是本领域公知的。例如，非天然存在的氨基酸可以通过将合成氨酰基-tRNA包含到用于表达所述孔的IVTT系统中而引入。替代地，通过在特定氨基酸的合成(即非天然存在的)类似物存在下，在针对该特定氨基酸为营养缺陷型的大肠杆菌中表达所述单体，来引入非天然存在的氨基酸。在使用部分肽合成来产生所述孔的情况下，它们还可以通过裸露连接(naked ligation)而产生。
任何氨基酸均可用带正电的氨基酸取代。一个或多个不带电氨基酸、非极性氨基酸和/或芳香族氨基酸可以用一个或多个带正电的氨基酸取代。不带电的氨基酸没有净电荷。适宜的不带电的氨基酸包括，但不限于，半胱氨酸(C)、丝氨酸(S)、苏氨酸(T)、甲硫氨酸(M)、天冬酰胺(N)和谷氨酰胺(Q)。非极性氨基酸具有非极性侧链。适宜的非极性氨基酸包括，但不限于，甘氨酸(G)、丙氨酸(A)、脯氨酸(P)、异亮氨酸(I)、亮氨酸(L)和缬氨酸(V)。芳香族氨基酸具有芳香族侧链。适宜的芳香族氨基酸包括，但不限于，组氨酸(H)、苯丙氨酸(F)、色氨酸(W)和酪氨酸(Y)。优选地，一个或多个带负电的氨基酸用一个或多个带正电的氨基酸取代。适宜的带负电的氨基酸包括，但不限于，天冬氨酸(D)和谷氨酸(E)。
优选的引入包括，但不限于，以下取代：用K取代E，用R取代M，用H取代M，用K取代M，用R取代D，用H取代D，用K取代D，用R取代E，用H取代E，用R取代N，用R取代T，用R取代G。最优选地用K取代E。
可以引入或取代任何数目的带正电的氨基酸。例如，可以引入或取代1,2,5,10,15,20,25,30个或更多带正电的氨基酸。
更优选地通过中和一个或多个负电荷来增加净正电荷。所述一个或多个负电荷可以通过用一个或多个不带电的氨基酸、非极性氨基酸和/或芳香族氨基酸取代一个或多个带负电的氨基酸而进行替代来中和。去除负电荷能增加净正电荷。所述不带电的氨基酸、非极性氨基酸和/或芳香族氨基酸可以是天然存在的或非天然存在的。它们可以是合成的或经修饰的。适宜的不带电的氨基酸、非极性氨基酸和芳香族氨基酸如上文所述。优选的取代包括，但不限于，用Q取代E，用S取代E，用A取代E，用Q取代D，用N取代E，用N取代D，用G取代D，用S取代D。
可以取代任意数目和任意组合的不带电的氨基酸、非极性氨基酸和/或芳香族氨基酸。例如，可以取代1,2,5,10,15,20,25或30个或者更多不带电的氨基酸、非极性氨基酸和/或芳香族氨基酸。带负电的氨基酸可以用下述氨基酸取代：(1)不带电的氨基酸；(2)非极性氨基酸；(3)芳香族氨基酸；(4)不带电的氨基酸和非极性氨基酸；(5)不带电的氨基酸和芳香族氨基酸；和(5)非极性氨基酸和芳香族氨基酸；或(6)不带电的氨基酸、非极性氨基酸和芳香族氨基酸。
所述一个或多个负电荷可以通过在一个或多个带负电的氨基酸附近例如1,2,3或4个氨基酸范围内或在一个或多个带负电的氨基酸相邻处引入一个或多个带正电的氨基酸而中和。带正电和带负电的氨基酸的实例如上文所述。所述带正电的氨基酸可以用上文所述的任何方式引入，例如通过取代而引入。
优选地，通过引入一个或多个带负电的氨基酸和/或中和一个或多个正电荷来减少净正电荷。可以减少净正电荷的方法将从上文关于增加净正电荷的描述中清楚得知。上文描述的关于增加净正电荷的任何事实方案同样适用于减少净正电荷的情况，不同在于，电荷正好相反。特别地，所述一个或多个正电荷优选地通过用一个或多个不带电的氨基酸、非极性氨基酸和/或芳香族氨基酸取代一个或多个带正电的氨基酸而中和或者通过在一个或多个带正电的氨基酸附近例如1,2,3或4个氨基酸范围内或在一个或多个带正电的氨基酸相邻处引入一个或多个带负电的氨基酸而中和。
优选地增加或减少净负电荷。上文描述的关于增加或减少净正电荷的任何实施方案同样分别适用于减少或增加净负电荷的情况。
对于(c)，可用任何方式改变所述单体进行氢键合的能力。引入丝氨酸(S),苏氨酸(T),天冬酰胺(N),谷氨酰胺(Q),酪氨酸(Y)或组氨酸(H)，可增加所述单体的氢键合能力。优选地，所述一个或多个修饰为引入S,T,N,Q,Y和H中的一个或多个。可以引入S,T,N,Q,Y和H的任意组合。所述S,T,N,Q,Y和H中的一个或多个可通过添加而引入。所述S,T,N,Q,Y和H中的一个或多个优选通过取代而引入。适于引入这类残基的位置在下文更详细论述。
去除丝氨酸(S),苏氨酸(T),天冬酰胺(N),谷氨酰胺(Q),酪氨酸(Y)或组氨酸(H)，可减少所述单体的氢键合能力。优选地，所述一个或多个修饰为去除S,T,N,Q,Y和H中的一个或多个。可去除S,T,N,Q,Y和H的任意组合。所述S,T,N,Q,Y和H中的一个或多个可通过缺失而去除。所述S,T,N,Q,Y和H中的一个或多个优选地通过用氢键合能力较差的其他氨基酸例如丙氨酸(A),缬氨酸(V),异亮氨酸(I)和亮氨酸(L)进行取代而去除。
对于(d)，引入芳香族残基，例如苯丙氨酸(F),色氨酸(W),酪氨酸(Y)或组氨酸(H)，也可增加所述单体中的π-堆积。去除芳香族残基，例如苯丙氨酸(F),色氨酸(W),酪氨酸(Y)或组氨酸(H)，也可增加所述单体中的π-堆积。这类氨基酸可参照上文(a)中的论述而引入或去除。
对于(e)，根据本发明进行一个或多个修饰来改变所述单体的结构。例如，可去除、缩短或扩展一个或多个环形区域。这通常有利于多核苷酸进入或离开所述孔。所述一个或多个环形区域可以在所述孔的顺侧、所述孔的反侧或位于所述孔的两侧。替代地，所述孔的氨基末端和/或羧基末端的一个或多个区域可以扩展或删除。这通常会改变所述孔的尺寸和/或电荷。
从上文论述中清楚的是，引入某些氨基酸将增加所述单体与多核苷酸通过多于一种的机制进行相互作用的能力。例如，用H取代E将不仅依照(b)增加净正电荷(通过中和负电荷)而且将依照(c)增加所述单体进行氢键合的能力。
所述变体优选地包括在SEQ ID NO:2的下述位置中的一个或多个处的取代：M44,N46,N48,E50,R52,H58,D68,F70,E71,S74,E76,S78,Y79,S80,H81,S82,E84,E85,S86,Q87,S89,M90,E92,E94,E97,E102,H103,T104,T106,R115,Q117,N119,D121和D126。所述变体优选地包括在这些位置中的1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33或34位的取代。所述变体优选地包括在SEQ IDNO:2的下述位置中的一个或多个处的取代：D68,E71,S74,E76,S78,S80,S82,E84,E85,S86,Q87,S89,E92,E102,T104,T106,R115,Q117,N119和D121。所述变体优选地包括在这些位置中的1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19或20位的取代。经取代进入所述变体的氨基酸可以是天然存在的氨基酸或其非天然存在的衍生物。经取代进入所述变体的氨基酸可以是D-氨基酸。上文所列的每个位置均可用天冬酰胺(N),丝氨酸(S),谷氨酰胺(Q),精氨酸(R),甘氨酸(G),酪氨酸(Y),天冬氨酸(D),亮氨酸(L),赖氨酸(K)或丙氨酸(A)进行取代。
所述变体优选地包括SEQ ID NO:2的以下突变中的至少一个：
(a)44位点处的丝氨酸(S)；
(b)46位点处的丝氨酸(S)；
(c)48位点处的丝氨酸(S)；
(d)52位点处的丝氨酸(S)；
(e)58位点处的丝氨酸(S)；
(f)68位点处的丝氨酸(S)；
(g)70位点处的丝氨酸(S)；
(h)71位点处的丝氨酸(S)；
(i)76位点处的丝氨酸(S)；
(j)79位点处的丝氨酸(S)；
(k)81位点处的丝氨酸(S)；
(l)84位点处的丝氨酸(S),天冬氨酸(D)或谷氨酰胺(Q)；
(m)85位点处的丝氨酸(S)或赖氨酸(K)；
(n)87位点处的丝氨酸(S)；
(o)90位点处的丝氨酸(S)；
(p)92位点处的天冬酰胺(N)或谷氨酰胺(Q)；
(q)94位点处的丝氨酸(S)或天冬酰胺(N)；
(r)97位点处的丝氨酸(S)或天冬酰胺(N)；
(s)102位点处的丝氨酸(S)；
(t)103位点处的丝氨酸(S)；
(u)121位点处的天冬酰胺(N)或丝氨酸(S)；
(v)50位点处的丝氨酸(S)；
(w)94位点处的天冬酰胺(N)或丝氨酸(S)；
(x)97位点处的天冬酰胺(N)或丝氨酸(S)；
(y)121位点处的丝氨酸(S)或天冬酰胺(N)；
(z)126位点处的天冬酰胺(N)或谷氨酰胺(Q)或甘氨酸(G)；和
(aa)128位点处的丝氨酸(S)或天冬酰胺(N)。
所述变体可以包括任何数目的突变(a)至(aa)，例如1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26或27个所述突变。所述突变的优选组合见下文所述。被引入到所述变体中的氨基酸可以是天然存在的氨基酸或其非天然存在的衍生物。被引入到所述变体中的氨基酸可以是D-氨基酸。
所述变体优选包含SEQ ID NO:2的以下突变中的至少一个：
(a)68位点处的丝氨酸(S)；
(b)71位点处的丝氨酸(S)；
(c)76位点处的丝氨酸(S)；
(d)84位点处的天冬氨酸(D)或谷氨酰胺(Q)；
(e)85位点处的赖氨酸(K)；
(f)92位点处的天冬酰胺(N)或谷氨酰胺(Q)；
(g)102位点处的丝氨酸(S)；
(h)121位点处的天冬酰胺(N)或丝氨酸(S)；
(i)50位点处的丝氨酸(S)；
(j)94位点处的天冬酰胺(N)或丝氨酸(S)；
(k)97位点处的天冬酰胺(N)或丝氨酸(S)；和
(l)126位点处的天冬酰胺(N)或谷氨酰胺(Q)或甘氨酸(G)。
所述变体可以包括任何数目的突变(a)至(l)，例如1,2,3,4,5,6,7,8,9,10,11或12个所述突变。所述突变的优选组合见下文所述。被引入到所述变体中的氨基酸可以是天然存在的氨基酸或其非天然存在的衍生物。被引入到所述变体中的氨基酸可以是D-氨基酸。
所述变体可以包括在SEQ ID NO:2的约44位点到约126位点的区域外部的一个或多个额外修饰，所述额外修饰与上述区域内的修饰结合用于提高多核苷酸捕获和/或提高多核苷酸识别或区分。适宜的修饰包括，但不限于，在D35,E128,E135,E134和E167中的一个或多个处进行取代。特别地，通过在128,135,134和167位点中的一个或多个处的取代E来去除负电荷，可以提高多核苷酸捕获。在这些位点中的一个或多个处的E可以用上文所述的任何方式进行取代。优选地，E128,E135,E134和E167全部按上文所述进行取代。优选用A取代E。换言之，所述变体优选包含E128A,E135A,E134A和E167A中的一个或多个或者全部。另一优选的取代为D35Q。
在一优选的实施方案中，所述变体包含SEQ ID NO:2中的以下取代：
i.E84D和E85K中的一个或多个，例如两个；
ii.E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个，例如2,3,4,5或6个；
iii.E92N,E94N,E97N,D121N和D126N中的一个或多个，例如2,3,4或5个；
iv.E92N,E94N,E97N,D121N,D126N和E128N中的一个或多个，例如2,3,4,5或6个；
v.E76S,E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个，例如2,3,4,5,6或7个；
vi.E84Q,E85K,E92Q,E97S,D126G,E167A和E50S中的一个或多个，例如2,3,4,5,6或7个；
vii.E84Q,E85K,E92Q,E97S,D126G,E167A和E71S中的一个或多个，例如2,3,4,5,6或7个；
viii.E84Q,E85K,E92Q,E97S,D126G,E167A和E94S中的一个或多个，例如2,3,4,5,6或7个；
ix.E84Q,E85K,E92Q,E97S,D126G,E167A和E102S中的一个或多个，例如2,3,4,5,6或7个；
x.E84Q,E85K,E92Q,E97S,D126G,E167A和E128S中的一个或多个，例如2,3,4,5,6或7个；
xi.E84Q,E85K,E92Q,E97S,D126G,E167A和E135S中的一个或多个，例如2,3,4,5,6或7个；
xii.E84Q,E85K,E92Q,E97S,D126G,E167A和D68S中的一个或多个，例如2,3,4,5,6或7个；
xiii.E84Q,E85K,E92Q,E97S,D126G,E167A和D121S中的一个或多个，例如2,3,4,5,6或7个；
xiv.E84Q,E85K,E92Q,E97S,D126G,E167A和D134S中的一个或多个，例如2,3,4,5,6或7个；
xv.E84D,E85K和E92Q中的一个或多个，例如2或3个；
xvi.E84Q,E85K,E92Q,E97S,D126G和E135S中的一个或多个，例如1,2,3,4,5或6个；
xvii.E85K,E92Q,E94S,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xviii.E76S,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xix.E71S,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xx.D68S,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xxi.E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3或4个；
xxii.E84Q,E85K,E92Q,E97S,H103S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxiii.E84Q,E85K,M90S,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxiv.E84Q,Q87S,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxv.E84Q,E85S,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xxvi.E84S,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xxvii.H81S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxviii.Y79S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxix.F70S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxx.H58S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxxi.R52S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxxii.N48S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxxiii.N46S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxxiv.M44S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4,5或6个；
xxxv.E92Q和E97S中的一个或多个，例如两个；
xxxvi.E84Q,E85K,E92Q和E97S中的一个或多个，例如1,2,3或4个；
xxxvii.E84Q和E85K中的一个或多个，例如两个；
xxxviii.E84Q,E85K和D126G中的一个或多个，例如1,2或3个；
xxxix.E84Q,E85K,D126G和E167A中的一个或多个，例如1,2,3或4个；
xl.E92Q,E97S和D126G中的一个或多个，例如1,2或3个；
xli.E84Q,E85K,E92Q,E97S和D126G中的一个或多个，例如1,2,3,4或5个；
xlii.E84Q,E85K,E92Q,E97S和E167A中的一个或多个，例如1,2,3,4或5个；
xliii.E84Q,E85K,E92Q,D126G和E167A中的一个或多个，例如1,2,3,4或5个；
xliv.E84Q,E85K,E97S,D126G和E167A中的一个或多个，例如1,2,3,4或5个；
xlv.E84Q,E92Q,E97S,D126G和E167A中的一个或多个，例如1,2,3,4或5个；
xlvi.E85K,E92Q,E97S,D126G和E167A中的一个或多个，例如1,2,3,4或5个；
xlvii.E84D,E85K和E92Q中的一个或多个，例如1,2或3个；
xlviii.E84Q,E85K,E92Q,E97S,D126G,E167A和D121S中的一个或多个，例如1,2,3,4,5,6或7个；
xlix.E84Q,E85K,E92Q,E97S,D126G,E167A和D68S中的一个或多个，例如1,2,3,4,5,6或7个；
l.E84Q,E85K,E92Q,E97S,D126G,E167A和E135S中的一个或多个，例如1,2,3,4,5,6或7个；
li.E84Q,E85K,E92Q,E97S,D126G,E167A和E128S中的一个或多个，例如1,2,3,4,5,6或7个；
lii.E84Q,E85K,E92Q,E97S,D126G,E167A和E102S中的一个或多个，例如1,2,3,4,5,6或7个；
liii.E84Q,E85K,E92Q,E97S,D126G,E167A和E94S中的一个或多个，例如1,2,3,4,5,6或7个；
liv.E84Q,E85K,E92Q,E97S,D126G,E167A和E71S中的一个或多个，例如1,2,3,4,5,6或7个；
lv.E84Q,E85K,E92Q,E97S,D126G,E167A和E50S中的一个或多个，例如1,2,3,4,5,6或7个；
lvi.E76S,E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个，例如1,2,3,4,5,6或7个；
lvii.E92N,E94N,E97N,D121N,D126N和E128N中的一个或多个，例如1,2,3,4,5或6个；
lviii.E92N,E94N,E97N,D121N和D126N中的一个或多个，例如1,2,3,4或5个；或
lix.E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个，例如1,2,3,4,5或6。
在上述中，第一个字母是指SEQ ID NO:2中被替代的氨基酸，数字是指在SEQ IDNO:2中的位置，第二个字母是指替换第一个字母所代表的氨基酸的氨基酸。因此，E84D是指84位点处的谷氨酸(E)被天冬氨酸(D)取代。
所述变体可以包括i至lix的任一个中的任意数目的取代，例如1,2,3,4,5,6或7个。所述变体优选包括上述i至lix的任一个中所示的所有取代。
在一优选的实施方案种，所述变体包括上述i至xv的任一个中的取代。所述变体可以包括i至xv的任一个中的任意数目的取代，例如1,2,3,4,5,6或7个。所述变体优选包括上述i至xv的任一个中所示的所有取代。
如果所述一个或多个修饰是用于提高所述单体识别或区分多核苷酸的能力，则优选在进行上述用于提高多核苷酸捕获的修饰之外进行所述一个或多个修饰，例如E84Q,E85K,E92Q,E97S,D126G和E167A。
对所识别区域进行的一个或多个修饰可以是指，用在胞溶素的同源物或旁系同源物(paralogue)的相应位置存在的氨基酸取代所述区域中的一个或多个氨基酸。胞溶素的同源物的四个实例在SEQ ID NO:16至19中示出。这类取代的优点是，它们可能导致突变体单体形成孔，因为其同源单体也能形成孔。
除了上面所讨论的特定的突变外，所述变体可包括其他的突变。这些突变不一定提高所述单体与多核苷酸相互作用的能力。所述突变可以利于例如表达和/或纯化。基于氨基酸的相似性，变体与SEQ ID NO:2的整个长度的氨基酸序列具有至少50％同源性。更优选地，基于氨基酸的相似性，所述变体与SEQ ID NO:2的整个长度的氨基酸序列具有至少55％,至少60％,至少65％,至少70％,至少75％,至少80％,至少85％,至少90％同源性，更优选地至少95％,97％或99％同源性。在100或更长,例如125,150,175或200或更长的连续氨基酸的长度上，可以具有至少80％,例如至少85％,90％或95％的氨基酸相似性(“严格同源性(hard homology)”)。
可使用本领域的标准方法测定同源性。例如UWGCG包提供了BESTFIT程序，该程序可用于计算同源性，例如使用其默认设置(Devereux等人(1984)核酸s Research 12,p387-395)。PILEUP算法和BLAST算法可用于计算同源性或比对序列(line up sequence)(例如识别等价残基或对应序列(通常基于其默认设置))，例如Altschul S.F.(1993)J Mol Evol36:290-300；Altschul,S.F等人(1990)J Mol Biol 215:403-10中所描述的。
进行BLAST分析的软件可通过国家生物技术信息中心(National Center forBiotechnology Information)(http://www.ncbi.nlm.nih.gov/)而公开获得。这一算法包括，首先通过识别查询序列中W长度的短字(short words)来识别高得分序列对(HSP)，所述查询序列中W长度的字在与数据库序列中相同长度的字比对(align with)时能匹配或满足一些为正值的阈值评分T。T指的是邻近字的得分阈值(Altschul等人,supra)。这些初始邻近字的匹配记录(hits)用作开启检索以寻找包含它们的HSP的种子。该字匹配记录沿着每个序列向两个方向扩展到，直到累积比对得分(cumulative alignment score)增加为止。所述字匹配记录在每个方向的扩展在以下的时候停止：累积比对得分从其取得的最大值下降X量时；由于一个或多个负得分残基比对的积累而是累积得分趋于零或低于零时；或任一序列结束时。BLAST算法参数W、T和X决定比对的灵敏度和速度。BLAST程序使用默认设置：字长(W)为11，BLOSUM62得分矩阵(参见Henikoff and Henikoff(1992)Proc.Natl.Acad.Sci.USA 89:10915-10919)比对值(B)为50、期望值(E)为10,M＝5,N＝4,以及两条链的比较值。
BLAST算法对两个序列进行相似性的统计分析；参见例如Karlin and Altschul(1993)Proc.Natl.Acad.Sci.USA 90:5873-5787。由BLAST算法提供的相似性的一个量度为最小和概率(P(N))，该最小和概率表示两个氨基酸序列偶然发生配对的概率。例如，如果在一个序列与另一个序列相比，最小和概率小于约1，优选小于约0.1，更优选地小于约0.01，最优选地小于约0.001，则上述第一个序列被认为与上述第二个序列相似。
可以对SEQ ID NO:2的除了上述那些氨基酸序列之外的氨基酸序列进行氨基酸取代，例如多达1,2,3,4,5,10,20或30个取代。保守取代是将氨基酸用相似化学结构、相似化学性能或相似侧链体积的其他氨基酸进行替换。被引入的氨基酸可以具有与它们所替代的氨基酸相似的极性、亲水性、疏水性、碱性、酸性、中性或电荷。替代地，所述保守取代可以在之前存在芳香族或脂肪族氨基酸的地方引入另外的芳香族或脂肪族氨基酸。保守的氨基酸改变是本领域公知的，并且可以根据下表1中所限定的20个主要氨基酸的性质进行选择。如果氨基酸具有相似的极性，则这还可以通过参照表2中氨基酸侧链的亲水性大小(hydropathy scale)来确定。
表1–氨基酸的化学性质
表2-亲水性大小
所述变体可以包含一个或多个位于上述指定区域外部的取代，其中氨基酸被胞溶素的同源物和旁系同源物中相应位置处的那些氨基酸替换。旁系同源物的同源物的四个实例示于SEQ ID NO:16至19中。
SEQ ID NO:2的氨基酸序列的一个或多个氨基酸残基可以另外从上述变体中缺失。可以缺失多达1,2,3,4,5,10,20或30个残基，或者更多。
变体可以包括SEQ ID NO:2的片段。所述片段保留有形成孔的活性。这可以按上文所述进行试验。片段可以具有至少50,100,150,200或250个氨基酸长度。这类片段可以用于产生本发明的孔。由于根据本发明SEQ ID NO:2的约44位点到约126位点的区域可以通过一个或多个缺失进行修饰，因此片段不用必须含有整个区域。因此，比未修饰区域的长度短的片段也是本发明能想到的。片段优选含有形成SEQ ID NO:2的结构域的孔。片段更优选地含有SEQ ID NO:2的约44位点到约126位点的区域，该区域可根据本发明进行修饰。
一个或多个氨基酸可以替代地或另外地被添加到上述的变体中。在SEQ ID NO:2的变体的氨基酸序列(包括其片段)的氨基末端或羧基末端可以含有延伸(extension)。所述延伸可以很短，例如从1到10个氨基酸长度。替代地，所述延伸可以较长，例如多达50或100个氨基酸。根据本发明，载体蛋白可以融合到氨基酸序列。其他融合蛋白在下文更详细地论述。
如上文所述，变体为具有从SEQ ID NO:2的氨基酸序列变化而来的氨基酸序列且保留有其形成孔的能力的多肽。变体通常含有SEQ ID NO:2的负责形成孔的区域，即约44位点到约126位点，并且该区域根据本发明按如上所述进行修饰。如上所述，其可以含有该区域的片段。除了本发明的修饰外，SEQ ID NO:2的变体可以包括一个或多个另外的修饰，例如取代、添加或缺失。这些修饰优选地位于所述变体对应SEQ ID NO:2的约位点1至约位点43和约位点127至约位点297的长度中(即根据本发明修饰的区域的外部)。
可以修饰所述突变体单体以有助于对它们的识别或纯化，所述修饰例如通过下述进行：通过添加组氨酸残基(hist标签)、天冬氨酸残基(asp标签)、抗生蛋白链菌素标签或flag标签，或通过添加信号序列来促进它们从细胞的分泌——当多肽并不天然含有该序列时。引入遗传标签的替换方案是通过化学反应将标签连接到所述孔上的天然或工程位点。其一个例子为将凝胶迁移试剂与工程连接在所述孔外部的半胱氨酸进行反应。这被证明是一种用于分离溶血素异源寡聚体的方法(Chem Biol.1997Jul；4(7):497-505)。
所述突变体单体可以用揭示标签进行标记。所述揭示标签可以是能对孔进行检测的任何适宜标签。适宜的标签包括，但不限于，荧光分子、放射性同位素例如125I、35S，酶、抗体、抗原、多核苷酸、聚乙二醇(PEG)、肽和配体如生物素。
所述突变体单体还可以使用D-氨基酸制备。例如，所述突变体单体可以包含L-氨基酸和D-氨基酸的混合物。这是本领域制备所述蛋白质或肽所常规使用的。
所述突变体单体包含一个或多个特异性修饰，以有利于与多核苷酸的相互作用。所述突变体单体还可以包含其他非特异性修饰，只要它们不影响孔的形成即可。很多非特异性侧链修饰是本领域已知的，并可以针对所述突变体单体的侧链进行。这类修饰包括，例如，通过与醛进行反应然后用NaBH4还原而进行的氨基酸的还原性烷基化，用甲基乙酰亚胺酯(methylacetimidate)进行的脒基化，或用乙酸酐进行的酰化。
所述突变体单体可以使用本领域已知的标准方法制备。所述单体可以合成或通过重组的方式制备。例如，所述单体可以通过体外翻译和转录(IVTT)进行合成。用于制备孔单体的适宜方法在国际申请号PCT/GB09/001690(公布号WO 2010/004273),PCT/GB09/001679(公布号WO 2010/004265)或PCT/GB10/000133(公布号WO 2010/086603)中有论述。将孔插入膜中的方法在下文进行论述。
编码突变体单体的多核苷酸序列可以使用本领域标准方法得到并复制。这类序列在下文更详细论述。编码突变体单体的多核苷酸序列可以使用本领域标准技术在细菌宿主细胞中进行表达。所述突变体单体可以在细胞中通过重组表达载体进行多肽的原位表达而制备。所述表达载体可选地携带有诱导型启动子以控制所述多肽的表达。
突变体单体可以从制备孔的生物体或在重组表达后，通过任何蛋白质液相色谱系统进行纯化，而大规模制备，如下文所述。通常的蛋白质液相色谱系统包括FPLC、AKTA系统、Bio-Cad系统、Bio-Rad生物系统和Gilson HPLC系统。然后所述突变体单体可以被引入到天然存在的膜或人工膜中而用于本发明。将孔插入到膜中的方法在下文论述。
在一些实施方案中，对所述突变体单体进行化学修饰。可用任何方式在任何位点对所述突变体单体进行化学修饰。所述突变体单体优选通过下述进行化学修饰：将分子连接到一个或多个半胱氨酸(半胱氨酸连接)、将分子连接到一个或多个赖氨酸、将分子连接到一个或多个非天然氨基酸、表位的酶修饰或末端修饰。适于进行这些修饰的方法是本领域公知的。适宜的非天然氨基酸包括，但不限于，4-叠氮基-L-苯丙氨酸(Faz)，以及LiuC.C.and Schultz P.G.,Annu.Rev.Biochem.,2010,79,413-444的图1中的编号为1-71的氨基酸中任意一个。所述突变体单体可以通过任何分子的连接而进行化学修饰。例如，所述突变体单体可以通过连接聚乙二醇(PEG)、核酸如DNA、染料、荧光团或生色团而进行化学修饰。
在一些实施方案中，所述突变体单体用分子适配体进行化学修饰，以有利于含所述单体的孔与目标分析物、目标核苷酸或目标多核苷酸之间的相互作用。适配体的存在提高了孔与核苷酸或多核苷酸的主客体化学(host-guest chemistry)并由此提高了由所述突变体单体形成的孔的测序能力。主客体化学的原理是本领域公知的。所述适配体对提高孔与核苷酸或多核苷酸相互作用的孔的物理或化学性能具有影响。所述适配体可以改变所述孔的桶状结构或通道的电荷，或者改变与核苷酸或多核苷酸的特异性相互作用或结合从而有利于其与所述孔的相互作用。
所述分子适配体优选为环状分子如环糊精，能杂交的物质、DNA结合剂或相互螯合剂(interchelator)、肽或肽类似物、合成的聚合物、芳香族平面分子、带正电的小分子或能够进行氢键合的小分子。
所述适配体可以是环状的。环状适配体优选具有与所述孔相同的对称性。
所述适配体通常通过主客体化学与分析物、核苷酸或多核苷酸相互作用。所述适配体通常能够与核苷酸或多核苷酸相互作用。所述适配体含有一个或多个能够与核苷酸或多核苷酸相互作用的化学基团。所述一个或多个化学基团优选通过非共价相互作用与核苷酸或多核苷酸相互作用，所述非共价相互作用例如疏水性相互作用、氢键合、范德华力、π-阳离子相互作用和/或静电力。所述一个或多个能够与核苷酸或多核苷酸相互作用的化学基团优选带正电。所述一个或多个能够与核苷酸或多核苷酸相互作用的化学基团更优选地含有氨基。所述氨基可连接到伯、仲或叔碳原子。所述适配体甚至更优选地含有氨基的环，例如6,7,8或9个氨基的环。所述适配体最优选地含有6或9个氨基的环。质子化的氨基的环可与核苷酸或多核苷酸中带负电的磷酸基相互作用。
可通过所述适配体与含有所述突变体单体的所述孔之间的主客体化学来促进所述适配体在所述孔内的正确定位。所述适配体优选含有一个或多个能够与所述孔内的一个或多个氨基酸相互作用的化学基团。所述适配体更优选地含有一个或多个能够与所述孔内的一个或多个氨基酸通过非共价相互作用而进行相互作用的化学基团，所述非共价相互作用例如疏水性相互作用、氢键合、范德华力、π-阳离子相互作用和/或静电力。能够与所述孔内的一个或多个氨基酸相互作用的化学基团通常为羟基或胺。所述羟基可连接到伯、仲或叔碳原子。所述羟基可与所述孔内不带电的氨基酸形成氢键。有利于所述孔与所述核苷酸或多核苷酸之间的相互作用的任何适配体均可使用。
适宜适配体包括，但不限于，环糊精、环肽和葫芦脲(cucurbituril)。所述适配体优选为环糊精或其衍生物。所述环糊精或其衍生物可以为Eliseev,A.V.,and Schneider,H-J.(1994)J.Am.Chem.Soc.116,6081-6088中公开的任何环糊精或其衍生物。所述适配体更优选地为七-6-氨基-β-环糊精(am7-βCD),6-单脱氧-6-单氨基-β-环糊精(am1-βCD)或七-(6-脱氧-6-胍基)-环糊精(gu7-βCD)。gu7-βCD中的胍基具有比am7-βCD中的伯胺高得多的pKa并因此带更多的正电。该gu7-βCD适配体可以用于增加核苷酸在所述孔内的停留时间，从而增加测得的剩余电流的准确性以及增加高温下的碱基检测速率(base detectionrate)或降低数据采集速率。
如下文更详细论述的，如果使用3-(2-吡啶二硫代)丙酸琥珀酰亚胺酯(SPDP)交联剂，则所述适配体优选为七(6-脱氧-6-氨基)-6-N-单(2-吡啶基)二硫代丙酰基-β-环糊精(am6amPDP1-βCD)。
更适宜的适配体包括含有8个糖单元(并因此具有八重对称性)的γ-环糊精。所述γ-环糊精可以包含连接体分子或可以被修饰为含有在上述β-环糊精实例中所用的全部或大部分经修饰的糖单元。
所述分子适配体优选共价连接到所述突变体单体。所述适配体可使用本领域已知的任何方法共价连接到所述孔。所述适配体通常通过化学连接而连接。如果所述分子适配体经由半胱氨酸连接而连接，则所述一个或多个半胱氨酸优选已通过取代被引入所述突变体。当然，本发明的突变体单体可以在272and 283位点中的一个或这两个处含有半胱氨酸残基。所述突变体单体可以通过将分子适配体连接到所述半胱氨酸中的一个或这两个上而进行化学修饰。替代地，所述突变体单体可以通过将分子连接到一个或多个在其他位点处引入的半胱氨酸或非天然氨基酸如FAz而进行化学修饰。
半胱氨酸残基的反应活性可以通过修饰相邻残基而提高。例如，侧翼精氨酸、组氨酸或赖氨酸残基的碱基会将半胱氨酸硫醇基的pKa改变成更具反应活性的S-基团的pKa。半胱氨酸残基的反应活性可以通过硫醇保护基团例如dTNB来保护。它们可以与突变体单体的一个或多个半胱氨酸残基进行反应，之后连接一连接体。
所述分子可以直接连接到所述突变体单体。所述分子优选使用连接体，如化学交联剂或肽连接体，连接到所述突变体单体。
适宜的化学交联剂是本领域公知的。优选的交联剂包括2,5-二氧代吡咯烷-1-基3-(吡啶-2-基二硫烷基)丙酸酯、2,5-二氧代吡咯烷-1-基4-(吡啶-2-基二硫烷基)丁酸酯和2,5-二氧代吡咯烷-1-基8-(吡啶-2-基二硫烷基)辛酸酯。最优选的交联剂为3-(2-吡啶基二硫代)丙酸琥珀酰亚胺酯(SPDP)。通常所述分子在所述分子/交联剂复合体共价连接到所述突变体单体之前而共价连接到双功能交联剂，但是其也可在双功能交联剂/单体复合体连接到所述分子之前而将所述双功能交联剂共价连接到所述单体。
所述连接体优选对二硫苏糖醇(DTT)具有抗性。适宜的连接体包括，但不限于，基于碘乙酰胺和基于马来酰亚胺的连接体。
在其他实施方案中，所述单体可以连接到多核苷酸结合蛋白。这样形成了可在本发明方法中使用的模块测序系统。对多核苷酸结合蛋白的论述如下。
所述多核苷酸结合蛋白可以共价连接到所述突变体单体。所述蛋白质可以使用本领域已知的任何方法共价连接到所述孔。所述单体和蛋白质可以是通过化学融合的或基因融合的。如果整个构造从单个多核苷酸序列表达而来，则所述单体和蛋白是通过基因融合的。孔到多核苷酸结合蛋白的基因融合在国际申请号PCT/GB09/001679(公布号WO 2010/004265)中有论述。
如果所述多核苷酸结合蛋白通过半胱氨酸连接而连接，则所述一个或多个半胱氨酸优选已通过取代被引入到所述突变体。这类取代通常在同源物中具有较低保守性环形区域中进行，较低的保守性是指可以忍受突变或插入。因此它们适于连接多核苷酸结合蛋白。这类取代通常在SEQ ID NO:2的1至43和127至297位残基中进行。半胱氨酸残基的反应活性可以通过上文所述的修饰而提高。
所述多核苷酸结合蛋白可以直接连接到突变体单体或经由一个或多个连接体而连接。所述多核苷酸结合蛋白可以使用国际申请号PCT/GB10/000132(公布号WO 2010/086602)中所述的杂交连接体(hybridization linker)而连接到所述突变体单体。替代地，可以使用肽连接体。肽连接体为氨基酸序列。所述肽连接体的长度、柔性和亲水性通常被设计为，其不妨碍所述单体和分子的功能。优选的柔性肽连接体具有2至20个例如4,6,8,10或16个丝氨酸和/或甘氨酸的氨基酸长度。更优选的柔性连接体包括(SG)1,(SG)2,(SG)3,(SG)4,(SG)5和(SG)8，其中S为丝氨酸，G为甘氨酸。优选的刚性连接体具有2至30个例如4,6,8,16或24个脯氨酸的氨基酸长度。更优选的刚性连接体包括(P)12，其中P为脯氨酸。
所述突变体单体可以用分子适配体和多核苷酸结合蛋白进行化学修饰。
制备突变体胞溶素单体
本发明还提供了一种提高包含SEQ ID NO:2中所示序列的胞溶素单体表征多核苷酸的能力的方法。该方法包括，在SEQ ID NO:2的约44位点到约126位点的区域中进行一个或多个修饰，所述修饰能改变所述单体与多核苷酸相互作用的能力且不影响所述单体用于形成孔的能力。上文针对突变体胞溶素单体和下文针对多核苷酸表征所论述的任何实施方案同样适用于本发明的该方法。
构造
本发明还提供了一种构造，所述构造包含两个或多个共价连接的源自胞溶素的单体，其中所述单体中的至少一个为本发明的突变体胞溶素单体。本发明的构造保持其形成孔的能力。本发明的一个或多个构造可以用于形成用于表征目标分析物的孔。本发明的一个或多个构造可以用于形成用于表征目标多核苷酸例如测序目标多核苷酸的孔。所述构造可以包含2,3,4,5,6,7,8,9或10个或者更多单体。所述两个或多个单体可以相同或不同。
至少一个所述构造中的单体为本发明的突变体单体。所述构造中的其他单体不用必须为本发明的突变体单体。例如，至少一个单体可以包含SEQ ID NO:2中所示的序列。所述构造中的至少一个单体可以为SEQ ID NO:2中的旁系同源物或同源物。适宜的同源物示于SEQ ID NO:16至19中。
替代地，至少一个单体可以含有SEQ ID NO:2的变体，基于氨基酸的相似性，所述变体与SEQ ID NO:2的整个序列具有至少50％同源性，但是不包括任何本发明突变体单体所需的特异性突变。更优选地，基于氨基酸的相似性，所述变体与SEQ ID NO:2的整个序列具有至少55％,至少60％,至少65％,至少70％,至少75％,至少80％,至少85％,至少90％，更优选地至少95％,97％或99％同源性。所述变体可以为上述的片段或任何其他变体。本发明的构造也可以含有SEQ ID NO:16,17,18或19的变体，基于氨基酸的相似性，所述变体与SEQ ID NO:16,17,18或19的整个序列具有至少50％同源性或至少为上述提及的任何同源性水平中的任何一个。
所述构造中的所有单体均可以为本发明突变体单体。所述突变体单体可以相同或不同。在一更优选的实施方案中，所述构造含有两个单体，并且所述单体中至少一个为本发明突变体单体。
所述单体可以是通过基因融合的。如果整个构造从单个多核苷酸序列表达而来，则单体是通过基因融合。所述单体的编码序列可以以任意方式组合以形成编码所述构造的单个多核苷酸序列。基因融合在国际申请号PCT/GB09/001679(公布号WO 2010/004265)中有论述。
所述单体可以在任何构造中通过基因融合。所述单体可以通过其末端氨基酸进行融合。例如，一个单体中的氨基末端可以融合到另一个单体的羧基末端。
两个或多个单体可以直接通过基因融合在一起。所述单体优选地使用连接体进行基因融合。所述连接体可以被设计成使所述单体具有移动性。优选的连接体为氨基酸序列(即肽连接体)。上文论述的任何肽连接体均可以使用。
在另一个优选的实施方案中，所述单体是通过化学融合的。如果单体例如通过化学交联剂进行化学连接，则它们是通过化学融合的。上文论述的任何化学交联剂均可以使用。所述连接体可以连接到被引入到突变体单体中的一个或多个半胱氨酸残基或非天然氨基酸，例如Faz。替代地，所述连接体可以连接到所述构造中的单体之一的末端。单体通常经由SEQ ID NO:2的1至43和127至297位残基中的一个或多个而连接。
如果一个构造含有不同的单体，则可以通过保持连接体的浓度远超过所述单体的浓度来避免单体自身之间的交联。替代地，在使用两个连接体情况下可以使用“锁与钥匙(lock and key)”设置(arrangement)。每个连接体只有一端可以一起反应而形成更长的连接体，所述连接体的另一端各自与不同单体反应。这类连接体在国际申请号PCT/GB10/000132(公布号WO2010/086602)中有描述。
本发明还提供了制备本发明构造的方法。所述方法包括将至少一个本发明的突变体胞溶素单体共价连接到源自胞溶素的一个或多个单体。上文针对本发明构造所描述的任何实施方案同样适用于制备所述构造的方法。
多核苷酸
本发明还提供了编码本发明突变体单体的多核苷酸序列。所述突变体单体可以是上文论述的任何突变体单体。所述多核苷酸序列优选含有基于核苷酸相似性与SEQ ID NO:1的整个序列具有至少50％,60％,70％,80％,90％或95％同源性的一序列。在300或更长,例如375,450,525或600或更长的连续氨基酸的长度上，可以具有至少80％,例如至少85％,90％或95％的核苷酸相似性(“严格同源性(hard homology)”)。同源性可以按上文所述计算。在遗传密码简并(degeneracy)的基础上，所述多核苷酸序列可以含有不同于SEQ IDNO:1的序列。
本发明还提供了编码本发明的任意基因融合构造的多核苷酸序列。所述多核苷酸优选包括如上所述的SEQ ID NO:1所示两个或更多序列或者其变体。
多核苷酸序列可以使用本领域标准方法得到并复制。编码野生型胞溶素的染色体DNA可以从产生有机体如赤子爱胜蚓(Eisenia fetida)的孔中提取。编码所述孔单体的基因可以使用涉及特定引物的PCR扩增。然后可以使扩增的序列经历定向诱变。适宜的定向诱变方法是本领域已知的，包括例如联合链反应(combine chain reaction)。编码本发明构造的多核苷酸可使用公知技术，例如在Sambrook,J.and Russell,D.(2001).MolecularCloning:A Laboratory Manual,第3版.Cold Spring Harbor Laboratory Press,ColdSpring Harbor,NY中记载的那些制成。
得到的多核苷酸序列之后可被并入一重组的可复制载体中，例如克隆载体中。所述载体可用于复制相容宿主细胞中的多核苷酸。因此，所述多核苷酸序列可以通过下述而制备：将一多核苷酸引入可复制载体中、将所述载体引入一相容宿主细胞然后使所述宿主细胞在能使所述载体进行复制的条件下生长。所述载体可以从宿主细胞中回收。适于克隆多核苷酸的宿主细胞是本领域已知的，并在下文有更详细描述。
所述多核苷酸序列可以被克隆到适宜的表达载体中。在表达载体中，所述多核苷酸序列通常可操作地连接到控制序列，所述控制序列能够通过宿主细胞提供对编码序列的表达。这类表达载体可用于表达孔亚基。
术语“可操作地连接”是指所述组分以能使其按其预定方式发挥功能的关系进行并置(juxtaposition)。“可操作地连接”到编码序列的控制序列以下述方式连接：使所述编码序列在与所述控制序列相容的条件下进行表达。可以在载体中引入相同或不同多核苷酸序列的多个拷贝。
然后可以将所述表达载体引入适宜的宿主细胞中。因此，本发明的突变体单体或构造可通过下述而产生：将多核苷酸序列插入表达载体中、将所述载体引入到相容的细菌宿主细胞中，然后使所述宿主细胞在能使所述多核苷酸序列的表达的条件下生长。重组体表达的单体或构造可以自组装到宿主细胞膜的孔中。替代地，以此方式产生的重组体孔可以被从所述宿主细胞中去除并被插入到另外的膜中。当产生含有至少两个不同亚基的孔时，所述不同亚基可以如上文所述在不同宿主细胞中被单独表达、被从所述宿主细胞中去除并被组装到一单独膜的孔中，例如绵羊红细胞膜或含鞘磷脂的脂质体。
所述载体可以是例如质粒、病毒或噬菌体，它们提供有复制的起点、可选地提供有用于表达所述多核苷酸序列的启动子和可选地提供有所述启动子的调节因子。所述载体可以含有一个或多个选择性标记基因，例如四环素耐受性基因。启动子及其他表达调控信号可以被选择为，与设计所述表达载体所针对的宿主细胞相容。通常使用T7,trc,lac,ara或λL启动子。
所述宿主细胞通常以较高的水平来表达孔亚基。用多核苷酸序列转化的宿主细胞被选择为，与转化所述宿主细胞所用的表达载体相容。所述宿主细胞通常是细菌的宿主细胞，优选地为大肠杆菌的宿主细胞。任何具有λDE3溶素原(lysogen)，例如C41(DE3),BL21(DE3),JM109(DE3),B834(DE3),TUNER，Origami和Origami B的细胞，可以表达含有T7启动子的载体。除上文所列条件外，可以使用Proc Natl Acad Sci U S A.2008 Dec 30；105(52):20647-52中引用的任何方法来表达所述胞溶素蛋白。
孔
本发明还提供了多种孔。本发明的孔对于表征分析物是理想的。本发明的孔尤其对于表征例如测序多核苷酸是理想的，因为它们能够以高敏感性区分不同核苷酸。所述孔可用于表征核酸，例如DNA和RNA，包括测序所述核酸和识别单碱基的变化。本发明的孔甚至可以区分甲基化的和未甲基化的核苷酸。本发明的孔对碱基的分辨率出人意料的高。所述孔表明了所有四个DNA核苷酸几乎完全分离。所述孔可以基于在所述孔中的停留时间和流经所述孔的电流而进一步用于区分脱氧胞苷单磷酸(dCMP)和甲基-dCMP。
本发明的孔还可以在许多条件下区分不同核苷酸。特别地，所述孔将在有利于对多核苷酸的表征(例如测序)的条件下区分核苷酸。本发明的孔区分不同核苷酸的程度可通过改变施加的电势、盐浓度、缓冲剂、温度和是否存在添加剂，例如脲、甜菜碱和DTT，来控制。这使得可以很好的调节(fine-tuned)所述孔的功能，特别是当测序时。这将在下文更详细论述。本发明的孔还可以用于从与一个或多个单体的相互作用中而不是在逐个核苷酸的基础上来识别多核苷酸聚合物。
本发明的孔可以是是分离的、基本分离的、纯化的或基本纯化的孔。如果本发明的孔完全不含任何其他组分，例如脂质或其他孔，则本发明的孔是分离的或纯化的孔。如果孔混合有不影响其预期用途的载体或稀释剂，则所述孔为基本分离的。例如，如果孔以下述形式存在：含有小于10％、小于5％、小于2％或小于1％的其他组分，例如脂质或其他孔，则所述孔为基本分离的或基本纯化的。替代地，本发明的孔可以存在于脂质双分子层中。
本发明的孔可以作为单独的孔或单个孔而存在。替代地，本发明的孔可以两个或更多孔的同源或异源孔群或多个孔而存在。
同源寡聚孔
本发明还提供了包含相同的本发明突变体单体的源自胞溶素的同源寡聚孔。所述单体在其氨基酸序列方面是相同的。本发明的同源寡聚孔对于表征例如测序多核苷酸是理想的。本发明的同源寡聚孔可以具有上文所述的任何优点。本发明的具体同源寡聚孔的优点说明于实施例中。
所述同源寡聚孔可以含有任何数目的突变体单体。所述孔通常含有两个或多个突变体单体。所述突变体单体中的一个或多个优选地如上所述进行了化学修饰。换言之，对所述单体中的一个或多个进行化学修饰(并且其他单体没有进行化学修饰)并不妨碍所述孔为同源孔，只要每个所述单体的氨基酸序列相同即可。
制备胞溶素孔的方法在实施例及Yamaji等人,J.Biol.Chem.1998；273(9):5300-6中进行了描述。
异源寡聚孔
本发明还提供了包含至少一个本发明突变体单体的源自胞溶素的异源寡聚孔，其中所述单体中至少一个不同于其他单体。所述单体就其氨基酸序列而言不同于其他单体。本发明的异源寡聚孔对于表征例如测序多核苷酸是理想的。本发明的异源寡聚孔可以使用本领域中已知的方法制备(例如Protein Sci.2002 Jul；11(7):1813-24)。
所述异源寡聚孔含有足够单体以形成所述孔。所述单体可以是任何类型。所述孔通常含有两个或更多单体。
所述孔可以包含至少一个含有SEQ ID NO:2中所示序列的单体、其旁系同源物、其同源物，或其变体，所述变体不具有本发明突变体单体所需的突变。适宜的变体为上文针对本发明构造所述的任何变体，包括SEQ ID NO:2,16,17,18和19及其变体。在该实施方案中，其余单体优选为本发明的突变体单体。
在一优选实施方案中，所述孔含有(a)本发明的一个突变体单体，和(b)足够数目的用以形成所述孔的相同单体，其中(a)中的所述突变体单体不同于(b)中的所述相同单体。(b)中的所述相同单体优选含有SEQ ID NO:2中所示序列、其旁系同源物、其同源物或其变体，所述变体不具有本发明突变体单体所需的突变。
本发明的异源寡聚孔优选仅含有本发明的一个突变体胞溶素单体。
在另一优选的实施方案中，所述异源寡聚孔中所有单体均为本发明的突变体单体，并且这些单体中至少一个不同于其他单体。
在上述的所有实施方案中，所述突变体单体中的一个或多个优选如上所述进行化学修饰。在一个单体上存在化学修饰不会使所述孔为异源寡聚体孔。至少一个单体的氨基酸序列必须不同于其他单体的序列。制备孔的方法在下文更详细论述。
含有构造的孔
本发明还提供了包含至少一个本发明构造的孔。本发明构造包含两个或多个共价连接的源自胞溶素的单体，其中所述单体中至少一个是本发明的突变体胞溶素单体。换言之，构造必须包含多于一个的单体。所述孔中的单体中至少两个为本发明构造的形式。所述单体可以是任何类型。
孔通常包含(a)含有两个单体的一个构造，和(b)足够数目的用以形成所述孔的单体。所述构造可以是上文所述的任何构造。所述单体可以是上文所述的任何单体，包括本发明的发明的突变体单体在内。
另一典型的孔含有多于一个的本发明构造，例如两个、三个或四个本发明的构造。这类孔进一步含有足够数目的用以形成所述孔的单体。所述单体可以是上文所述的任何单体。本发明的另外的孔仅含有包含2个单体的构造。本发明的特定孔含有几个构造，每个构造含有两个单体。所述构造可以寡聚进入具有一构造的孔中，使得每个构造中仅一个单体有助于形成所述孔。通常地，所述构造的其他单体(即不形成所述孔的单体)将位于所述孔的外部。
可以如上文所述在所述构造中引入突变。所述突变可以是交替的，即，所述突变对于两个单体构造内的每个单体而言是不同的并且所述构造被装配成寡聚体，导致交替的修饰(alternating modifications)。换言之，含有MutA和MutB的单体被融合并装配，以形成A-B:A-B:A-B:A-B孔。替代地，所述突变可以是邻接的(neighbouring)，即相同单体被引入到构造中的两个单体内，然后使其与不同突变体单体寡聚。换言之，含有MutA的单体被融合，之后与含有MutB的单体寡聚，从而形成A-A:B:B:B:B:B:B。
在含有构造(construct-containing)的孔中，本发明的一个或多个单体可以如上文所述进行化学修饰。
制备本发明的孔
本发明还提供了一种制造本发明的孔的方法。所述方法包括，使至少一个本发明的突变体单体或至少一个本发明的构造与足够数目的本发明的突变体胞溶素单体、本发明的构造或源自胞溶素的单体寡聚，从而形成孔。如果所述方法涉及的是制备本发明的同源寡聚孔，则在所述方法中使用所有单体为具有相同氨基酸序列的本发明突变体胞溶素单体。如果所述方法涉及的是制备本发明的异源寡聚孔，则至少一个所述单体不同于其他单体。上述的关于本发明的孔的任何实施方案同样适用于制备所述孔的方法。
一种优选的制备本发明的孔的方法在实施例1中公开。
表征分析物的方法
本发明还提供了一种表征目标分析物的方法。所述方法包括，使所述目标分析物与本发明的孔接触，从而使所述目标分析物移动穿过所述孔。然后在所述分析物相对于所述孔移动时，使用本领域已知的标准方法测量所述目标分析物的一个或多个特征。优选在所述分析物移动穿过所述孔时，测量所述目标分析物的一个或多个特征。优选在跨所述孔施加电势时实施步骤(a)和(b)。如下文更详细论述的，施加的电势通常导致在所述孔和多核苷酸结合蛋白之间形成复合体。所述施加的电势可以是电压电势。替代地，所述施加的电势可以是化学电势。其一个例子是在两性分子层中使用盐梯度。Holden等人,J Am ChemSoc.2007 Jul 11；129(27):8650-5中公开了盐梯度。
本发明的方法是用于表征目标分析物。所述方法是用于表征至少一个分析物。所述方法可以涉及表征两个或多个分析物。所述方法可以包括表征任意数目的分析物，例如2,5,10,15,20,30,40,50,100个或更多分析物。
所述目标分析物优选为金属离子、无机盐、聚合物、氨基酸、肽、多肽、蛋白质、核苷酸、寡核苷酸、多核苷酸、染料、漂白剂、药物、诊断剂、消遣性药物(recreational drug)、爆炸性污染物或环境污染物。所述方法可以涉及表征相同类型的两个或多个分析物，例如两个或多个蛋白质、两个或多个核苷酸或两个或多个药物制剂。替代地，所述方法可以涉及表征不同类型的两个或多个分析物，例如一个或多个蛋白质、一个或多个核苷酸和一个或多个药物制剂。
所述目标分析物可以是细胞分泌物。替代地，所述目标分析物可以是存在于细胞内部的分析物，使得在实施本发明之前必须从细胞中提取出所述分析物。
所述分析物优选为氨基酸、肽、多肽和/或蛋白质。所述氨基酸、肽、多肽或蛋白质可以是天然存在的或非天然存在的。所述多肽或蛋白质内可以包含合成或经修饰的氨基酸。对氨基酸的许多不同类型的修饰是本领域已知的。适宜的氨基酸及其修饰见上文。对于本发明而言，可以理解的是，所述目标分析物可以通过本领域可获得的任何方法修饰。
所述蛋白质可以是酶、抗体、激素、生长因子或生长调节蛋白，例如细胞因子。所述细胞因子可以选自白细胞介素，优选IFN-1,IL-1,IL-2,IL-4,IL-5,IL-6,IL-10,IL-12和IL-13；干扰素，优选IL-γ，及其他细胞因子，例如TNF-α。所述蛋白质可以是细菌蛋白、真菌蛋白、病毒蛋白或寄生物衍生蛋白。
所述目标分析物优选为核苷酸、寡核苷酸或多核苷酸。核苷酸通常含有核碱基、糖和至少一个磷酸基。所述核碱基通常是杂环的。核碱基包括但不限于，嘌呤和嘧啶，更具体地，腺嘌呤、鸟嘌呤、胸腺嘧啶、尿嘧啶和胞嘧啶。所述糖通常为戊糖。核苷酸糖包括但不限于，核糖和脱氧核糖。所述核苷酸通常为核糖核苷酸或脱氧核糖核苷酸。所述核苷酸通常含有单磷酸，二磷酸或三磷酸。磷酸可以连接在核苷酸的5’或3’端。
核苷酸包括但不限于，腺苷单磷酸(AMP)、腺苷二磷酸(ADP)、腺苷三磷酸(ATP)、鸟苷单磷酸(GMP)、鸟苷二磷酸(GDP)、鸟苷三磷酸(GTP)、胸苷单磷酸(TMP)、胸苷二磷酸(TDP)、胸苷三磷酸(TTP)、尿苷单磷酸(UMP)、尿苷二磷酸(UDP)、尿苷三磷酸(UTP)、胞苷单磷酸(CMP)、胞苷二磷酸(CDP)、胞苷三磷酸(CTP)、5-甲基胞苷单磷酸、5-甲基胞苷二磷酸、5-甲基胞苷三磷酸、5-羟甲基胞苷单磷酸、5-羟甲基胞苷二磷酸、5-羟甲基胞苷三磷酸、环状腺苷单磷酸(cAMP)、环状鸟苷单磷酸(cGMP)、脱氧腺苷单磷酸(dAMP)、脱氧腺苷二磷酸(dADP)、脱氧腺苷三磷酸(dATP)、脱氧鸟苷单磷酸(dGMP)、脱氧鸟苷二磷酸(dGDP)、脱氧鸟苷三磷酸(dGTP)、脱氧胸苷单磷酸(dTMP)、脱氧胸苷二磷酸(dTDP)、脱氧胸苷三磷酸(dTTP)、脱氧尿苷单磷酸(dUMP)、脱氧尿苷二磷酸(dUDP)、脱氧尿苷三磷酸(dUTP)、脱氧胞苷单磷酸(dCMP)、脱氧胞苷二磷酸(dCDP)和脱氧胞苷三磷酸(dCTP)、5-甲基-2’-脱氧胞苷单磷酸、5-甲基-2’-脱氧胞苷二磷酸、5-甲基-2’-脱氧胞苷三磷酸、5-羟甲基-2’-脱氧胞苷单磷酸、5-羟甲基-2’-脱氧胞苷二磷酸和5-羟甲基-2’-脱氧胞苷三磷酸。所述核苷酸优选选自AMP,TMP,GMP,UMP,dAMP,dTMP,dGMP或dCMP。核苷酸可以是脱碱基的(abasic)(即缺少核苷碱基)。所述核苷酸可以包含另外的修饰。特别是，适宜的经修饰的核苷酸包括但不限于，2’氨基嘧啶(如2’-氨基胞苷和2’-氨基尿苷)、2’-羟基嘌呤(例如2’-氟嘧啶(例如2’-氟胞苷和2’氟尿苷)、羟基嘧啶(例如5’-α-P-硼烷基尿苷(borano uridine))、2’-O-甲基核苷酸(例如2’-O-甲基腺苷、2’-O-甲基鸟苷、2’-O-甲基胞苷和2’-O-甲基尿苷)、4’-硫代嘧啶(例如4’-硫代尿苷和4’-硫代胞苷)，核苷酸具有对核苷碱基的修饰(例如5-戊炔基-2’-脱氧尿苷、5-(3-氨基丙基)-尿苷和1,6-二氨基己基-N-5-氨基甲酰甲基尿苷)。
寡核苷酸是短的核苷酸聚合物，通常具有50个或更少的核苷酸，例如40个或更少、30个或更少、20个或更少、10个或更少，或者5个或更少的核苷酸。所述寡核苷酸可以包含上述任何核苷酸，包括脱碱基的和经修饰的核苷酸。本发明的方法优选用于表征目标多核苷酸。多核苷酸，例如核酸，是含有两个或多个核苷酸的大分子。所述多核苷酸或核酸可以含有任意核苷酸的任意结合。所述核苷酸可以使天然存在的或人工的。所述目标多核苷酸中的一个或多个核苷酸可以是经氧化的或甲基化的。所述目标多核苷酸中的一个或多个核苷酸可以是被破坏的。例如，所述多核苷酸可以含有嘧啶二聚体。所述二聚体通常与通过紫外线的破坏有关并且是皮肤黑素瘤的主要原因。所述目标多核苷酸中的一个或多个核苷酸可以通过例如标签或标记进行修饰。适宜的标签如上文所述。所述目标多核苷酸可以含有一个或多个间隔物。
核苷酸如上文所定义。存在于多核苷酸中的核苷酸通常包括，但不限于，腺苷单磷酸(AMP)、鸟苷单磷酸(GMP)、胸苷单磷酸(TMP)、尿苷单磷酸(UMP)、胞苷单磷酸(CMP)、环状腺苷单磷酸(cAMP)、环状鸟苷单磷酸(cGMP)、脱氧腺苷单磷酸(dAMP)、脱氧鸟苷单磷酸(dGMP)、脱氧胸苷单磷酸(dTMP)、脱氧尿苷单磷酸(dUMP)和脱氧胞苷一磷酸(dCMP)。所述核苷酸优选选自AMP,TMP,GMP,CMP,UMP,dAMP,dTMP,dGMP,dCMP和dUMP。
所述核苷酸可以是脱碱基的(即缺少核苷碱基)。
所述多核苷酸中的核苷酸可以按任何方式彼此连接。所述核苷通常通过它们的糖基和磷酸基进行连接，同在核酸中一样。所述核苷酸可以通过它们的核碱基连接，同在嘧啶二聚体中一样。
所述多核苷酸可以是单链的或双链的。至少所述多核苷酸的一部分优选为双链的。单链多核苷酸可以具有一个或多个与其杂交的引物，并因此包含一个或多个较短的双链多核苷酸区域。所述引物可以是作为目标多核苷酸的相同类型的多核苷酸或可以是不同类型的多核苷酸。
所述多核苷酸可以是核酸，诸如脱氧核糖核酸(DNA)或核糖核酸(RNA)。所述目标多核苷酸可包括与一条DNA链杂交的一条RNA链。所述多核苷酸可以是本领域已知的任何合成核酸，例如肽核酸(PNA)、甘油核酸(GNA)、苏糖核酸(TNA)、锁核酸(locked nucleicacid，LNA)，或其他具有核苷酸侧链的合成聚合物。
所述目标多核苷酸的全部或仅一部分可以使用该方法表征。所述目标多核苷酸可以具有任何长度。例如，所述多核苷酸可具有至少10,至少50,至少100,至少150,至少200,至少250,至少300,至少400或至少500个核苷酸对的长度。所述多核苷酸可以具有1000或更多个核苷酸对、5000或更多个核苷酸对长度，或100000或更多个核苷酸对长度。
所述目标分析物，例如目标多核苷酸，存在于任何适宜的样本中。本发明通常针对已知含有或怀疑其含有所述目标分析物，例如目标多核苷酸的样本进行实施。替代地，本发明可以针对样本实施来确认已知或预期存在于所述样本中的一个或多个目标分析物，例如一个或多个目标多核苷酸的相似性。
所述样本可以是生物样本。本发明可以针对由任何有机体或微生物体获得或提取的样本在体外实施。所述有机体或微生物体通常是古核的(archaean)、原核的或真核的，并通常属于以下五界之一：植物界、动物界、真菌界、无核原生物界和原生生物界。本发明可以针对由任何病毒获得或提取的样本在体外实施。所述样本优选为液体样本。所述样本通常包括患者的体液。所述样本可以是尿液、淋巴液、唾液、粘液或羊水，但优选为血液、血浆或血清。通常，所述样本来自人，但替代地，其可以是来自其他哺乳动物，例如来自商购的家畜，如马、牛、羊或猪，或替代地，可为宠物，如猫或狗。替代地，源自植物的样本通常获得自经济作物，例如谷类、豆类、水果或蔬菜，如小麦、大麦、燕麦、油菜、玉米、大豆、稻、香蕉、苹果、西红柿、马铃薯、葡萄、烟草、黄豆、扁豆、甘蔗、可可、棉花。
所述样本可以是非生物样本。所述非生物样本优选为液体样本。所述非生物样本的实例包括外科手术液、水，例如饮用水、海水或河水，以及用于实验室测试的试剂。
通常在分析前对所述样本进行处理，例如，通过离心或通过膜过滤掉不需要的分子或细胞，例如红血细胞。所述样本可以在获取后立即进行检测。所述样本通常也可以在分析前储存，优选在低于-70℃储存。
所述孔通常存在于膜中。本发明可以使用任何膜。适宜的膜是本领域已知的。所述膜优选包含鞘磷脂。所述膜优选为两性分子层。两性分子层是由两性分子，例如磷脂形成的层，具有至少一个亲水部分和至少一个亲脂或疏水部分。所述两性分子层可以是合成的或天然存在的。非天然存在的两性分子和形成单层的两性分子是本领域已知的，包括，例如，嵌段共聚物(Gonzalez-Perez等人,Langmuir,2009,25,10447-10450)。嵌段共聚物是两个或多个单体亚基聚合在一起而产生单个聚合物链的聚合材料。嵌段共聚物通常具有每个单体亚基的性能。然而，嵌段共聚物可以具有由单个亚基形成的聚合物所不具有的独特性能。嵌段共聚物是可以设计成，使所述单体亚基之一为疏水性的(即亲脂性的)，而其他亚基在水性介质中时为亲水性的。在此情况下，该嵌段共聚物可以具有两亲性质并且可以形成类似生物膜的结构。该嵌段共聚物可以是二嵌段的(由两个单体亚基构成)，但也可以由多于两个的单体亚基构成从而形成与两亲分子行为类似的更复杂排列。所述共聚物可以是三嵌段共聚物、四嵌段共聚物或五嵌段共聚物。
所述两性分子层可以是单层或双层的。所述两性分子层通常为平面脂质双分子层或支撑双分子层(supported bilayer)。
所述两性分子层通常是脂质双分子层。脂质双分子层是细胞膜的模型并被用作多个实验研究的优良平台。例如，脂质双分子层能通过单通道记录而用于对膜蛋白的体外研究。替代地，脂质双分子层可以用作生物传感器来检测多种物质的存在。所述脂质双分子层可以是任何的脂质双分子层。合适的脂质双分子层包括但不限于，平面脂质双分子层，支撑双分子层或脂质体。所述脂质双分子层优选为平面脂质双分子层。适宜的脂质双分子层公开于国际申请PCT/GB08/000563(公布号WO 2008/102121),国际申请No.PCT/GB08/004127(公布号WO 2009/077734)和国际申请No.PCT/GB2006/001057(公布号WO 2006/100484)中。
形成脂质双分子层的方法为本领域已知的。合适的方法公开在实施例中。脂质双分子层通常通过Montal和Mueller(Proc.Natl.Acad.Sci.USA.,1972；69:3561-3566)的方法形成，其中脂质单分子层穿过孔的任一侧负载在水溶液/空气界面上，所述孔垂直于所述界面。
Montal&Mueller的方法受欢迎的原因是，其成本经济并且是形成具有良好品质的适于蛋白孔嵌入脂质双分子层的相对简单的方法。其他常规的形成双分子层的方法包括脂质体双分子层的尖端浸渍(tip-dipping)、涂覆双分子层(painting bilayers)和膜片钳(patch-clamping)。
在一个优选实施方案中，所述脂质双分子层如国际申请No.PCT/GB08/004127(公布号WO 2009/077734)所述而形成。在另一个优选实施方案中，在另一个优选实施方案中，所述膜为固态层。固态层不来源于生物体。换言之，固态层不是由生物环境(例如有机体或细胞)获得或分离出的，或生物上可获得的结构合成制得的变体。固态层可以由有机和无机材料形成，所述有机和无机材料包括但不限于微电子材料；绝缘材料，例如Si3N4,A12O3,和SiO；有机和无机聚合物，例如聚酰胺，塑料如
或弹性体如双组分加成固化硅橡胶，和玻璃。所述固态层可以由单原子层如石墨烯形成，或只有几个原子厚的层形成。适宜的石墨烯层在国际申请No.PCT/US2008/010637(公布号WO 2009/035647)中公开。
所述方法通常使用以下物质实施：(i)含有孔的人工两性分子层，(ii)分离出的、天然存在的含有孔的脂质双分子层，或(iii)具有嵌入其中的孔的细胞。所述方法通常使用人工两性分子层例如人工脂质双分子层实施。所述层除孔之外还可以含有其他跨膜和/或膜内蛋白以及其他分子。适合的装置和条件如下所述。本发明的方法通常在体外实施。
所述分析物，例如目标多核苷酸，可以偶联到所述膜。这可以使用任何已知方法实现。如果所述膜是为两性分子层，例如脂质双分子层(如上文详细论述的)，则所述分析物，例如目标多核苷酸优选通过所述膜中存在的多肽或所述膜中存在的疏水锚(anchor)偶联至所述膜。所述疏水锚优选为脂质、脂肪酸、固醇、碳纳米管或氨基酸。
所述分析物，例如目标多核苷酸可以直接偶联到所述膜。所述分析物，例如目标多核苷酸优选通过连接体偶联到所述膜。优选的连接体包括但不限于，聚合物，例如多核苷酸、聚乙二醇(PEG)和多肽。如果多核苷酸直接偶联到所述膜，则由于所述膜与所述孔的内部之间的距离，表征不能进行到所述多核苷酸的末端，将丢失一些数据。如果使用连接体，则所述多核苷酸能够被表征完全。如果使用连接体，则所述连接体可以在任何位置连接到所述多核苷酸。所述连接体优选在尾部聚合物连接到所述多核苷酸。
所述偶联可以是稳定的或暂时的。对于某些应用，暂时性的偶联是优选的。如果一个稳定偶联的分子直接连接在多核苷酸的5’或3’端，则由于所述双分子层与所述孔的内部之间的距离，表征不能进行到所述多核苷酸的末端，将丢失一些数据。如果所述偶联是暂时性的，则当偶联的末端随机地变为没有双分子层时，所述多核苷酸不能被表征完全。与膜形成稳定或暂时性的连接的化学基团在下面更详细的描述。所述分析物，例如目标多核苷酸可以使用胆固醇或脂肪酰链暂时性地与两性分子层例如脂质双分子层偶联。可以使用任何具有6-30个碳原子长度的脂肪酰链，例如十六烷酸。
在优选实施方案中，将所述分析物，例如目标多核苷酸偶联到脂质双分子层。所述分析物，例如目标多核苷酸与合成脂质双分子层的偶联可以预先已用多种不同的共享策略(tethering strategies)实施。这些策略综述于下表3中。
表3
多核苷酸可以使用经修饰的亚磷酰胺在合成反应中官能化，使其能容易的与反应基团的加成兼容，所述反应基团诸如硫醇，胆固醇，脂质和生物素基团。这些不同的连接化学成分为多核苷酸提供了一系列连接选择。每个不同的修饰基团以稍微不同的方式连接到所述多核苷酸并且所述偶联不总是永久性的，使得多核苷酸在所述双分子层上有不同的停留时间。暂时性偶联的优点如上所述。
多核苷酸的偶联还能通过很多其他手段实现，使得反应性基团被添加到所述多核苷酸。之前已经有在DNA任一端添加反应性基团的报道。可以使用多核苷酸激酶和ATPγS在ssDNA的5’端添加硫醇基团(Grant,G.P.和P.Z.Qin(2007)."A facile method forattaching nitroxide spin labels at the 5'terminus of nucleic acids."Nucleic Acids Res 35(10):e77)。可以使用末端转移酶添加具有多种不同选择的化学基团，诸如生物素，硫醇或荧光素，将经修饰的寡核苷酸添加到ssDNA的3’端(Kumar,A.,P.Tchen,等人(1988)."Nonradioactive labeling of synthetic oligonucleotide probes withterminal deoxynucleotidyl transferase."Anal Biochem 169(2):376-82)。
替换地，反应性基团可以被认为是DNA短片段互补性添加到已经偶联到所述双分子层的DNA短片段，使得所述连接可以通过杂交实现。已经报道ssDNA的短片段的连接可以使用T4 RNA连接酶I实现(Troutt,A.B.,M.G.McHeyzer-Williams,等人(1992)."Ligation-anchored PCR:a simple amplification technique with single-sided specificity."Proc Natl Acad Sci U S A89(20):9823-5)。替换地，单链DNA或双链DNA可以连接到天然双链DNA上，然后通过加热变性或化学变性分开这两条链。对于天然双链DNA，可以在双链的一个或两个末端添加一段单链DNA或双链DNA。然后当双链被解链(melted)时，如果使用单链DNA进行连接，每条链将具有5’端或3’端的修饰，或者，如果使用双链DNA进行连接，每条链将具有5’端修饰，3’端修饰、或5’端修饰和3’端修饰。如果所述多核苷酸是人工合成链，所述偶联化学成分能在多核苷酸的化学合成过程中加入。例如，所述多核苷酸能使用具有反应性基团连接其上的引物合成。
一种常规的用于扩增基因组DNA片段的技术是使用聚合酶链反应(PCR)。这里，使用两个合成的寡核苷酸引物，可形成相同DNA片段的大量复制，其中对于每个拷贝，双链的每条链的5’将是一个人工合成的多核苷酸。通过使用具有反应性基团诸如胆固醇、硫醇、生物素或脂质的反义引物，每个扩增的目标DNA的拷贝将含有用于偶联的反应性基团。
本发明方法中使用的孔为本发明的孔(即含有至少一个本发明突变体单体或至少一个本发明构造的孔)。所述孔可以与上述方法中的任意一种进行化学修饰。所述孔优选地用能够与上述目标分析物相互作用的共价适配体进行修饰。
所述方法优选地用于表征目标多核苷酸并且步骤(a)包括使目标多核苷酸与所述孔和多核苷酸结合蛋白接触，并且所述蛋白控制目标多核苷酸穿过所述孔的运动。所述多核苷酸结合蛋白可以是能够结合至所述多核苷酸并控制其穿过所述孔的运动的任何蛋白。确定蛋白是否结合到多核苷酸是本领域中已知的。所述蛋白通常与所述多核苷酸相互作用并修饰所述多核苷酸的至少一种性能。所述蛋白可以通过使所述多核苷酸裂开形成单独的核苷酸或更短的核苷酸链，例如二核苷酸或三核苷酸而修饰所述多核苷酸。所述部分可以通过将所述多核苷酸定向或将其移动至特定位置，即控制其移动，来修饰所述多核苷酸。
所述多核苷酸结合蛋白优选地为多核苷酸处理酶。多核苷酸处理酶为能够与多核苷酸相互作用并修饰所述多核苷酸的至少一种性能的多肽。所述酶可以通过使所述多核苷酸裂开形成单个的核苷酸或更短的核苷酸链，例如二核苷酸或三核苷酸而修饰所述多核苷酸。所述酶可以通过将多核苷酸定向或将其移动至特定位置来修饰所述多核苷酸。所述多核苷酸处理酶不需要显示出酶活性，只要其能够结合目标序列并控制其运动穿过所述孔即可。例如，所述酶可以被修饰为去除了其酶活性或可以在能防止其作为酶而起作用的条件下使用。所述条件将在下文更详细描述。
所述多核苷酸处理酶优选地源自核酸溶解酶(nucleolytic enzyme)。在所述酶的构造中使用的多核苷酸处理酶更优选地源自酶分类(EC)组3.1.11,3.1.13,3.1.14,3.1.15,3.1.16,3.1.21,3.1.22,3.1.25,3.1.26,3.1.27,3.1.30和3.1.31中任一组中的多个。所述酶可以是国际申请号PCT/GB10/000133(公布号WO 2010/086603)中公开的那些酶中的任一个。
优选的酶为聚合酶、核酸外切酶、解旋酶和拓扑异构酶，例如促旋酶。适宜的酶包括，但不限于，来自大肠杆菌的核酸外切酶I(SEQ ID NO:6)、来自大肠杆菌的核酸外切酶III(SEQ ID NO:8)、来自极端嗜热菌(T.thermophilus)的RecJ(SEQ ID NO:10)，以及噬菌体λ核酸外切酶(SEQ ID NO:12)和其变体。含有SEQ ID NO:10中所示序列或其变体的三个亚基相互作用而形成三聚体核酸外切酶。所述酶可以是Phi29 DNA聚合酶(SEQ ID NO:4)或其变体。所述酶可以是解旋酶或源自解旋酶。通常的解旋酶为Hel308,RecD或XPD，例如Hel308 Mbu(SEQ ID NO:15)或其变体。
SEQ ID NO:4,6,8,10,12或15的变体为具有从SEQ ID NO:4,6,8,10,12或15的氨基酸序列变化而来的氨基酸序列并保持多核苷酸结合能力的酶。所述变体可以包括能促进多核苷酸的结合和/或促进其在高盐浓度和/或室温下的活性的修饰。
基于氨基酸的相似性，变体优选与SEQ ID NO:4,6,8,10,12或15的氨基酸序列的整个长度具有至少50％同源性。更优选地，基于氨基酸的相似性，所述变体多肽可以与SEQID NO:4,6,8,10,12或15的氨基酸序列的整个序列具有至少55％,至少60％,至少65％,至少70％,至少75％,至少80％,至少85％,至少90％且更优选地至少95％,97％或99％同源性。在200或更长、例如230,250,270或280或更长的连续氨基酸长度上，可以具有至少80％,例如至少85％,90％或95％的氨基酸相似性(“严格同源性”)。同源性按上文所述确定。所述变体可用上文针对SEQ ID NO:2所论述的方式中的任一种与野生型序列进行区分。所述酶可以如上文所述共价连接到所述孔。
使用纳米孔测序多核苷酸只要有两种策略，即标准测序和核酸外切酶测序。本发明的方法可以涉及标准测序或核酸外切酶测序。
在标准测序中，所述DNA顺着或逆着施加电势穿过纳米孔而移位。逐渐地或进行性地作用在双链DNA上的核酸外切酶可用在所述孔的顺侧上以使剩余的单链在施加的电势下穿过，或者在反向电势下用在所述孔的反侧上。同样地，解开双链DNA的解旋酶也可以类似的方式使用。也可以使用聚合酶。还有的测序应用可能需要逆着施加电势进行链移位，但是DNA必须在反向电势或没有电势的情况下首先被所述酶“捕获”。然后随着在结合之后电势被切换回，所述链从顺侧到反侧穿过所述孔并通过电流保持延伸的构造。单链DNA核酸外切酶或单链DNA依赖性聚合酶可用作分子马达，将最近移位的单链以受控和逐步的方式逆着施加的电势(从反侧到顺侧)穿过所述孔而拉回。
在一个实施方案中，表征目标多核苷酸的方法包括使目标序列与孔和解旋酶接触。在所述方法中可以使用任何解旋酶。解旋酶可以按两种模式相对于所述孔而工作。首先，优选地使用解旋酶来实施所述方法，使得所述解旋酶控制目标序列顺着由施加的电压产生的电场穿过所述孔的运动。在这种模式中，DNA的5’端首先被捕获到所述孔中，然后所述酶控制所述DNA进入到所述孔中的运动，使得目标序列顺着电场穿过所述孔直到其最终移位到所述双分子层的反侧。替代地，所述方法优选这样实施：使得所述解旋酶控制所述目标序列逆着由施加的电压产生的电场穿过所述孔的运动。在这种模式下，DNA的3’端首先被捕获到所述孔中，然后所述酶控制所述DNA穿过所述孔的运动，使得目标序列逆着施加的电场从所述孔中被拉出直到其完全退回到所述双分子层的顺侧。
在核酸外切酶测序中，核酸外切酶从目标多核苷酸的一端释放单个的核苷酸并按下文所述识别这些单个的核苷酸。在另一个实施方案中，表征目标多核苷酸的方法包括使目标序列与孔和核酸外切酶接触。上文论述的核酸外切酶中的任一种均可在所述方法中使用。所述酶可以如上文所述共价连接到所述孔。
核酸外切酶是通常结合到多核苷酸的一端并且从该端一次酶解所述序列一个核苷酸的酶。所述核酸外切酶可以沿着5′倒3′的方向或3′到5′的方向酶解所述多核苷酸。多核苷酸的结合有核酸外切酶的一端通常通过选择所用的酶和/或使用本领域中已知的方法来确定。在多核苷酸的任意一端的羟基或帽状结构(cap structure)通常可以用于防止或促进所述核酸外切酶结合至所述多核苷酸的特定端。
所述方法包括使所述多核苷酸与所述核酸外切酶接触，从而使所述核苷酸从所述多核苷酸的一端以一定速率被酶解，该速率允许一部分的核苷酸能如上文所述被表征或识别。实施上述操作的方法是本领域公知的。例如，使用埃德曼降解(Edman degradation)来从多肽的末端顺次酶解各单个氨基酸，使得所述氨基酸可以使用高效液相色谱法(HPLC)进行识别。类似的方法也可以在本发明中使用。
核酸外切酶发挥功能的速率通常比野生型核酸外切酶的最佳速率慢。本发明方法中核酸外切酶的适宜活性速率包括每秒酶解0.5-1000个核苷酸，每秒酶解0.6-500个核苷酸，每秒酶解0.7-200个核苷酸，每秒酶解0.8-100个核苷酸，每秒酶解0.9-50个核苷酸，或每秒酶解1-20或10个核苷酸。所述速率优选为每秒酶解1,10,100,500或1000个核苷酸。核酸外切酶的适宜活性速率可以多种方式实现。例如，根据本发明可以使用具有降低的最佳活性速率的变体核酸外切酶。
本发明的方法包括测量目标分析物例如目标多核苷酸的一个或多个特征。所述方法可以包括测量目标分析物例如目标多核苷酸的两个、三个、四个或五个或者更多个特征。对于目标多核苷酸而言，所述一个或多个特征优选地选自(i)目标多核苷酸的长度，(ii)目标多核苷酸的相似性，(iii)目标多核苷酸的序列，(iv)目标多核苷酸的二级结构，和(v)目标多核苷酸是否被修饰。(i)到(v)的任何组合均可以根据本发明进测定。
对于(i)，多核苷酸的长度可以利用目标多核苷酸与所述孔之间相互作用的数目进行测定。
对于(ii)，多核苷酸的相似性可以通过多种方式进行测定。多核苷酸的相似性可以联合目标多核苷酸序列的测定进行测定或者在不测定目标多核苷酸序列的情况下进行测定。前者是直接的；对所述多核苷酸进行测序，并由此进行识别。后者可以多种方式完成。例如，可以测定多核苷酸中特定模序(motif)的存在(不测定多核苷酸的其余序列)。替代地，在所述方法中特定电和/或光信号的测定可以识别来自特定来源的目标多核苷酸。
对于(iii)，多核苷酸的序列可以如前文所述进行测定。适宜的测序方法，特别是使用电测量的那些方法，在Stoddart D等人,Proc Natl Acad Sci,12；106(19):7702-7，Lieberman KR等人,J Am Chem Soc.2010；132(50):17961-72，以及国际申请WO 2000/28312中有描述。
对于(iv)，二级结构可以多种方式测定。例如，如果所述方法涉及电测量，则二级结构可以利用流经孔的停留时间的变化或电流的变化进行测定。这使得能够对单链和双链多核苷酸区域进行区分。
对于(v)，可以测定任何修饰的存在与否。所述方法优选包括确定所述目标多核苷酸是否用一个或多个蛋白质或一个或多个标记物、标签或间隔物通过甲基化、氧化、损伤，进行了修饰。特定的修饰将导致与孔的特定的相互作用，这可使用下述方法测定。例如，可以基于孔与每个核苷酸的相互作用过程中流经所述孔的电流，来区分胞嘧啶与甲基胞嘧啶。
本发明还提供了一种评估目标多核苷酸的序列的方法。本发明进一步提供了一种对目标多核苷酸进行测序的方法。
可以进行多种不同类型的测量。这包括但不限于：电测量和光学测量。可能的电测量包括：电流测量、阻抗测量，隧道测量(Ivanov AP等人，Nano Lett.2011Jan 12；11(1):279-85)，以及FET测量(国际申请WO 2005/124888)。奥尼GV等人，冯科学仪器厂。2010年1月；81(1)：014301)。光学测量可以与电测量结合(Soni GV等人,Rev SciInstrum.2010Jan；81(1):014301)。所述测量可以是跨膜电流测量，例如对流经所述孔的离子电流的测量。
电测量可以使用标准的单通道记录设备进行，如Stoddart D等人,Proc NatlAcad Sci,12；106(19):7702-7,Lieberman KR等人,J Am Chem Soc.2010；132(50):17961-72,以及国际申请WO-2000/28312中所述。替代地，电测量可以使用多通道系统进行，例如国际申请WO-2009/077734和国际申请WO-2011/067559中描述的所述。
在优选的实施方案中，所述方法包括：
(a)使目标多核苷酸与本发明的孔和多核苷酸结合蛋白接触，使得所述目标多核苷酸移动穿过所述孔并且所述结合蛋白控制所述目标多核苷酸穿过所述孔的运动；和
(b)当所述多核苷酸相对于所述孔移动时，测量流经所述孔的电流，其中，所述电流表示所述目标多核苷酸的一个或多个特征并由此表征所述目标多核苷酸。
所述方法可以使用适于研究孔被插入膜中的膜/孔系统的任何设备进行。所述方法可以使用适于跨膜孔感测的任何设备进行。例如，所述设备包括含水溶液的室和将所述室分成两部分的屏障。所述屏障具有孔穴，其中所述的含有孔的膜形成其中。
所述方法可以使用国际申请号PCT/GB08/000562(WO 2008/102120)中所述设备实施。
所述方法可以包括测量当分析物例如目标多核苷酸相对于所述孔移动时流经所述孔的电流。因此所述设备可以还包括能够施加电势并测量穿过膜和孔的电信号的电路。所述方法可以使用膜片钳或电压钳进行。所述方法优选包括使用电压钳。
本发明的方法可以包括测量当分析物例如目标多核苷酸相对于所述孔移动时流经所述孔的电流。测量流经跨膜蛋白孔的离子电流的适宜条件是本领域已知的并在实施例中有公开。所述方法通常通过所述跨膜和孔施加电压而实施。所用电压通常为+2V至-2V，通常-400mV至+400mV。所用电压优选在具有以下下限和上限的范围，所述下限选自-400mV,-300mV,-200mV,-150mV,-100mV,-50mV,-20mV和0mV并且所述上限独立地选自+10mV,+20mV,+50mV,+100mV,+150mV,+200mV,+300mV和+400mV。所用电压更优选在100mV到240mV范围内，最优选在120mV到220mV的范围内。可通过对孔施加提高的电势来提高对不同核苷酸的识别。
所述方法通常在任何载荷子例如金属盐(如碱金属盐)、卤盐(如氯化物盐(如碱金属氯化物盐))的存在下实施。载荷子可包括离子液体或有机盐，例如四甲基氯化铵、三甲基苯基氯化铵、苯基三甲基氯化铵，或1-乙基-3-甲基咪唑鎓氯。在上面论述的示例性设备中，所述盐存在于所述室的水溶液中。通常使用氯化钾(KCl)、氯化钠(NaCl)或氯化铯(CsCl)。优选KCl。所述盐浓度可以是饱和的。所述盐浓度可以是3M或更低并且通常为0.1-2.5M,0.3-1.9M,0.5-1.8M,0.7-1.7M,0.9-1.6M或1M-1.4M。所述盐浓度优选为150mM-1M。所述方法优选使用至少0.3M，例如至少0.4M,至少0.5M,至少0.6M,至少0.8M,至少1.0M,至少1.5M,至少2.0M,至少2.5M或至少3.0M的盐浓度实施。高的盐浓度能提供高的信噪比并使得在正常电流波动的背景下，代表核苷酸的存在的电流能被识别。
所述方法通常在缓冲剂的存在下实施。在上文所述的示例性设备中，所述缓冲剂存在于所述室的水溶液中。任何缓冲剂均可以在本发明方法中使用。通常，所述缓冲剂为HEPES。另一个适合的缓冲剂为Tris-HCl缓冲剂。所述方法通常在4.0-12.0,4.5-10.0,5.0-9.0,5.5-8.8,6.0-8.7或7.0-8.8或7.5-8.5的pH下进行实施。所述pH优选约为7.5。
所述方法可在0℃-100℃,15℃-95℃,16℃-90℃,17℃-85℃,18℃-80℃,19℃-70℃,或20℃-60℃下实施。所述方法通常在室温下实施。所述方法可选地在能支持酶功能的温度下例如约37℃实施。
所述方法通常在游离的核苷酸或游离的核苷酸类似物以及促进多核苷酸结合蛋白的作用的酶的辅因子存在下实施，所述多核苷酸结合蛋白例如解旋酶或核酸外切酶。所述游离的核苷酸可以是上述所有单个多核苷酸中的一个或多个。所述游离的核苷酸包括但不局限于，腺苷单磷酸(AMP),腺苷二磷酸(ADP),腺苷三磷酸(ATP),鸟苷单磷酸(GMP),鸟苷二磷酸(GDP),鸟苷三磷酸(GTP),胸苷单磷酸(TMP),胸苷二磷酸(TDP),胸苷三磷酸(TTP),尿苷单磷酸(UMP),尿苷二磷酸(UDP),尿苷三磷酸(UTP),胞苷单磷酸(CMP),胞苷二磷酸(CDP),胞苷三磷酸(CTP),环状腺苷单磷酸(cAMP),环状鸟苷单磷酸(cGMP),脱氧腺苷单磷酸(dAMP),脱氧腺苷二磷酸(dADP),脱氧腺苷三磷酸(dATP),脱氧鸟苷单磷酸(dGMP),脱氧鸟苷二磷酸(dGDP),脱氧鸟苷三磷酸(dGTP),脱氧胸苷单磷酸(dTMP),脱氧胸苷二磷酸(dTDP),脱氧胸苷三磷酸(dTTP),脱氧尿苷单磷酸(dUMP),脱氧尿苷二磷酸(dUDP),脱氧尿苷三磷酸(dUTP),脱氧胞苷单磷酸(dCMP),脱氧胞苷二磷酸(dCDP)和脱氧胞苷三磷酸(dCTP)。所述游离核苷酸优选选自AMP,TMP,GMP,CMP,UMP,dAMP,dTMP,dGMP或dCMP。所述游离核苷酸优选为腺苷三磷酸(ATP)。所述酶的辅因子为使解旋酶发挥功能的因子。所述酶的辅因子优选为二价金属阳离子。所述二价金属阳离子优选为Mg2+,Mn2+,Ca2+或Co2+。所述酶的辅因子最优选为Mg2+。
所述目标多核苷酸可以与所述孔和多核苷酸结合蛋白以任何顺序接触。优选的是，当所述目标多核苷酸与所述蛋白和所述孔接触时，所述目标多核苷酸首先与所述蛋白形成复合体。然后，当跨所述孔施加电压时，所述目标多核苷酸/蛋白复合体与所述孔形成复合体并控制所述多核苷酸穿过所述孔的运动。
识别单独的核苷酸的方法
本发明还提供了表征单独的核苷酸的方法。换言之，目标分析物是单独的核苷酸。所述方法包括使所述核苷酸与本发明的孔接触使得所述核苷酸与所述孔相互作用，和测量在所述相互作用过程中流经所述孔的电流并由此表征所述核苷酸。因此，本发明涉及对单独的核苷酸的纳米孔感测。本发明还提供了识别单独的核苷酸的方法，包括测量在所述相互作用过程中流经所述孔的电流并由此确定所述核苷酸的相似性。可以使用上文所述的任何本发明的孔。所述孔优选用上文所述的分子适配体进行化学修饰。
如果电流以核苷酸特有的方式流经所述孔(即，如果检测到关于核苷酸的独特电流流经所述孔)，则存在核苷酸。如果电流没有以核苷酸特有的方式流经所述孔，则不存在核苷酸。
本发明可用于基于核苷酸对流经孔的电流所具有的不同影响来区分类似结构的核苷酸。各单独的核苷酸能从它们在与所述孔相互作用时的电流幅值而在单个分子水平上被识别。本发明也可以用于确定样本中是否存在特定的核苷酸。本发明也可以用于测量样本中特定核苷酸的浓度。
所述孔通常存在于膜中。所述方法可以使用上述任何适宜的膜/孔系统实施。
单独的核苷酸是单个核苷酸。单独的核苷酸是没有通过核苷酸键结合至另一核苷酸或多核苷酸的核苷酸。核苷酸键是指一个核苷酸的磷酸基之一被结合至另一核苷酸的糖基。单独的核苷酸通常为没有通过核苷酸键结合至另一个至少5,至少10,至少20,至少50,至少100,至少200,至少500,至少1000或至少5000个核苷酸的多核苷酸的核苷酸。例如，所述单独的核苷酸已从目标多核苷酸序列，例如DNA或RNA链中被酶解出。本发明的方法可用于识别任何核苷酸。所述核苷酸可以是上文论述的任何核苷酸。
所述核苷酸可以源自核酸序列例如核糖核酸(RNA)或脱氧核糖核酸的酶解。核酸序列可以使用本领域中已知的任何方法酶解。适宜的方法包括，但不限于，使用酶或催化剂的那些方法。核酸的催化酶解在Deck等人，Inorg.Chem.,2002；41:669-677中有公开。
来自单个多核苷酸的单独核苷酸可以以顺序方式与所述孔接触，以对整个或部分的多核苷酸进行测序。对多核苷酸的测序已在上文详细论述。
所述核苷酸可以与膜的任一侧上的所述孔接触。所述核苷酸可以被引入所述膜的任一侧上的所述孔。所述核苷酸可以与所述膜的一侧接触，该侧允许所述核苷酸穿过所述孔到达所述膜的另一侧。例如，所述核苷酸与所述孔的一端接触，所述孔在其天然环境中允许离子或小分子，例如核苷酸进入到所述孔的桶状结构或通道中，由此使所述核苷酸可以穿过所述孔。在这种情况下，所述核苷酸在通过孔的桶状结构或通道穿过所述膜时与所述孔和/或适配体相互作用。替代地，所述核苷酸可以与所述膜的一侧接触，该侧允许所述核苷酸经由所述适配体或结合所述适配体而与所述孔相互作用，与所述孔分离，并保留在所述膜的同一侧上。本发明提供了能固定所述适配体位置的孔。结果，所述核苷酸优选地与所述孔的能使所述适配体与所述核苷酸相互作用的一端接触。
所述核苷酸可以与所述孔以任何方式和在任何位点相互作用。如上文所述，所述核苷酸优选地经由所述适配体或结合所述适配体而可逆地结合至所述孔。所述核苷酸最优选地在其穿过跨膜的所述孔时经由所述适配体或结合所述适配体而可逆地结合至所述孔。所述核苷酸还可在其穿过跨膜的所述孔时经由所述适配体或结合所述适配体而可逆地结合至所述孔的桶状结构或通道。
在核苷酸和所述孔之间相互作用的过程中，所述核苷酸以核苷酸所特有的方式影响流经所述孔的电流。例如，特定的核苷酸将在特定的平均时间段内以特定的程度减少流过所述孔的电流。换言之，对于特定核苷酸而言流经所述孔的电流是独特的。可以实施对照实验来确定特定核苷酸对流经所述孔的电流的影响。然后可将对测试样本实施本发明方法得到的结果与由所述对照实验得到的结果相比较，来识别样本中的特定核苷酸或确定样本中是否存在特定核苷酸。以代表特定核苷酸的方式影响流经所述孔的电流的频率可以用于确定样本中核苷酸的浓度。还可以计算出样本中不同核苷酸的比例。例如，可以计算出dCMP与甲基-dCMP的比例。
所述方法可以包括使用上述的任何设备、样本或条件。
形成传感器的方法
本发明还提供一种形成用于表征目标多核苷酸的传感器的方法。所述方法包括：在本发明的孔和多核苷酸结合蛋白例如解旋酶或核酸外切酶之间形成复合体。所述复合体可以通过使所述孔和所述蛋白在目标多核苷酸的存在下接触而形成然后跨所述孔施加电势。如上所述，所施加的电势可以是化学电势或电压电势。替代地，所述复合体可以通过将所述孔共价连接到所述蛋白而形成。共价连接的方法是本领域中已知的，并且在例如国际申请号PCT/GB09/001679(公布号WO 2010/004265)和PCT/GB10/000133(公布号WO 2010/086603)中被公开。所述复合体为用于表征目标多核苷酸的传感器。所述方法优选包括在本发明的孔和解旋酶之间形成复合体。上述任何实施方案同样适用于该方法。
本发明还提供一种用于表征目标多核苷酸的传感器。所述传感器包括在本发明的孔和多核苷酸结合蛋白之间形成的复合体。上述的任何实施方案同样适用于本发明的传感器。
试剂盒
本发明还提供了用于表征目标多核苷酸例如测序目标多核苷酸的试剂盒。所述试剂盒包括(a)本发明的孔和(b)多核苷酸结合蛋白，例如解旋酶或核酸外切酶。上述的任何实施方案同样适用于本发明的试剂盒。
本发明的试剂盒可另外包括一个或多个能实施上述任何实施方案的其他试剂或仪器。所述试剂或仪器包括以下的一个或多个：合适的缓冲剂(水溶液)、用于从受体获得样本的工具(例如容器或含有针的仪器)、用于扩增和/或表达多核苷酸序列的工具、上文定义的膜，或者电压钳或膜片钳设备。试剂可以以干态存在于所述试剂盒中，使得液体样本使该试剂重悬(resuspend)。可选地，所述试剂盒还可包括能使该试剂盒在本发明方法中使用的说明或关于该方法可以用于哪种病人的详细资料。可选地，所述试剂盒可包括核苷酸。
设备本发明还提供了用于表征例如测序样本中的目标多核苷酸的设备。所述设备可以包括(a)多个本发明的孔和(b)多个多核苷酸结合蛋白，例如解旋酶或核酸外切酶。所述设备可以是用于分析分析物的任何常规设备，例如阵列或芯片。
所述设备优选包括：
传感器装置，能支撑多个孔并可操作地使用所述孔和蛋白来实施多核苷酸的表征或测序；
-至少一个存储器，用于容纳实施表征或测序的材料；
-流体学系统，配置成从所述至少一个存储器可控地向所述传感器装置供应材料；和
-多个容器，用于接收各样本，所述流体学系统被配置成选择性地从所述容器向所述传感器装置供应所述样本。
所述装置可以是国际申请号PCT/GB10/000789(公布号WO 2010/122293),国际申请号PCT/GB10/002206(尚未公布)或国际申请号PCT/US99/25679(公布号WO 00/28312)中描述的任何装置。
以下实施例用于说明本发明:
实施例1–孔的产生
DNA合成
用于胞溶素的多肽在GenScript USA Inc.进行合成并使用NdeI和HindIII限制位点克隆到pT7载体中。为了表达的目的在DNA的起点放置Met(ATG)的密码子，并在DNA的结束翻译的一端放置两个终止密码子(TAA TGA)。
蛋白表达和寡聚
使用用于环状DNA的大肠杆菌T7-S30提取系统通过耦联体外转录和翻译(IVTT)而生成蛋白。蛋白在含有脂质囊泡的鞘磷脂(SM)的存在下进行表达，以促进在单体单元表达时的寡聚。为制备SM囊泡，将0.5mL的25mg/mL的SM的原液(Avanti Polar Lipids,目录号860062C)的氯仿溶液放置在37℃，以蒸发掉氯仿。一旦氯仿蒸发，就向瓶中添加5mL的TE缓冲液(10mM Tris,1mM EDTA,pH 8.0)以溶解脂质。然后将混合物涡旋约1分钟并用氮气快速冷冻。然后将脂质混合物在37℃解冻，涡旋并再次快速冷冻。将其重复5-6次。为在脂质囊泡的存在下生成100uL的IVTT蛋白，通过在20,000g下自旋(spinning)约10分钟将25μL制得的SM脂质囊泡沉淀。一旦除去上清液，就根据厂商的说明向所述沉淀(pellet)中添加IVTT试剂盒(Invitrogen Expressway Maxi Expression Module,目录号45-4001)的组分、甲硫氨酸L-[35S](Perkin Elmer,产品编号NEG009A005MC,比活度(specific activity):>1000Ci(37.0TBq)/mMole)和DNA模板。简言之，将20uL的大肠杆菌的slyD-提取物、20uL的不含氨基酸的2.5X IVPS反应缓冲液、1.25uL的不含蛋氨酸的50mM氨基酸、0.5uL的75mM蛋氨酸、0.5uL的甲硫氨酸L-[35S]、1.0uL的T7酶混合物、2.5uL的400ng/uL(1ug)DNA模板和4.25uL的无核糖核酸酶水下添加到模板沉淀中并在37℃孵育30分钟。然后将50uL进料缓冲液添加到所述混合物中并在37℃另外孵育90分钟，所述进料缓冲液含有25uL的2X IVPS进料缓冲液、1.25uL的不含蛋氨酸的50mM氨基酸、0.5uL的75mM蛋氨酸、0.5uL的甲硫氨酸L-[35S]和22.75uL的无核糖核酸酶水。然后将样本在20,000g自旋10分钟，并除去上清液。向所述上清液中添加含有3X SDS的100uL Laemmli上样缓冲液(loading buffer)(1X)。然后将样本用7.5％的凝胶进行SDS-PAGE电泳。
蛋白的纯化
将所述凝胶在50℃在纸上真空干燥3小时(Whatman 3MM Chr)，并过夜暴露于X射线胶片(约18小时)。使用放射自显影照片(autoradiograph)作为模板，从干燥凝胶中切割蛋白寡聚物条带。在150uL TE缓冲液中再水合之后，除去纸张。然后将所述凝胶用一次性杵压碎，并将浆料通过Costar自旋-X离心管过滤器(0.22μm的孔CA膜，产品编号8160)通过在25,000g离心10分钟而过滤。然后取该蛋白溶液(滤液)用在平面脂质双分子层实验中。
使用与上文实施例1中所述类似的过程，制备以下胞溶素突变体并纯化：-胞溶素-(E84Q/E85K/E92Q/E97S/D126G/E135S)(具有突变E84Q/E85K/E92Q/E97S/D126G/E135S的SEQ ID NO:2)，胞溶素-(E85K/E92Q/E94S/E97S/D126G)(具有突变E85K/E92Q/E94S/E97S/D126G的SEQ ID NO:2),胞溶素-(E76S/E85K/E92Q/E97S/D126G)(具有突变E76S/E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E71S/E85K/E92Q/E97S/D126G)(具有突变E71S/E85K/E92Q/E97S/D126G的SEQ ID NO:2),胞溶素-(D68S/E85K/E92Q/E97S/D126G)(具有突变D68S/E85K/E92Q/E97S/D126G的SEQ ID NO:2),胞溶素-(E85K/E92Q/E97S/D126G)(具有突变E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E84Q/E85K/E92Q/E97S/H103S/D126G)(具有突变E84Q/E85K/E92Q/E97S/H103S/D126G的SEQ ID NO:2)，胞溶素-(E84Q/E85K/M90S/E92Q/E97S/D126G)(具有突变E84Q/E85K/M90S/E92Q/E97S/D126G的SEQID NO:2)，胞溶素-(E84Q/Q87S/E85K/E92Q/E97S/D126G)(具有突变E84Q/Q87S/E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E84Q/E85S/E92Q/E97S/D126G)(具有突变E84Q/E85S/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E84S/E85K/E92Q/E97S/D126G)((具有突变E84S/E85K/E92Q/E97S/D126G的SEQ ID NO:2))，胞溶素-(H81S/E84Q/E85K/E92Q/E97S/D126G)((具有突变H81S/E84Q/E85K/E92Q/E97S/D126G的SEQ ID NO:2))，胞溶素(Y79S/E84Q/E85K/E92Q/E97S/D126G)(具有突变Y79S/E84Q/E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(F70S/E84Q/E85K/E92Q/E97S/D126G)(具有突变F70S/E84Q/E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(H58S/E84Q/E85K/E92Q/E97S/D126G)(具有突变H58S/E84Q/E85K/E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E92Q/E97S)(具有突变E92Q/E97S的SEQ ID NO:2)，胞溶素-(E84Q/E85K/E92Q/E97S)(具有突变E84Q/E85K/E92Q/E97S的SEQID NO:2)，胞溶素-(E84Q/E85K/D126G)(具有突变E84Q/E85K/D126G的SEQ ID NO:2)，胞溶素-(E84Q/E85K/D126G/E167A)(具有突变E84Q/E85K/D126G/E167A的SEQ ID NO:2)，胞溶素-(E92Q/E97S/D126G)(具有突变E92Q/E97S/D126G的SEQ ID NO:2)，胞溶素-(E84D/E85K/E92Q)(具有突变E84D/E85K/E92Q的SEQ ID NO:2)，胞溶素-(E84Q)(具有突变E84Q的SEQ IDNO:2)，胞溶素-(D126N)(具有突变D126N的SEQ ID NO:2)，胞溶素-(E92Q)(具有突变E92Q的SEQ ID NO:2)。
实施例2
该实施例说明了可以观察到野生型胞溶素(SEQ ID NO:2)纳米孔插入到1,2-二植烷酰-甘油基-3-磷酸胆碱脂质(DPhPC)双分子层中。在测试的实验条件下不可能观察到DNA捕获事件或任何解旋酶控制DNA移动。在该实施例中使用的一般方法和底物示于图1中并在该图附图标记进行了描述。
材料和方法
引物被设计为用于扩增PhiX174的～400的片段。这些引物的每一个5’端包括一50个核苷酸的非互补区域，可以是同源聚物延伸(homopolymeric stretch)或10个核苷酸同源聚合物部分的重复单元。此外，正向引物的5'端是“加帽的”以包括四个2'-O-甲基-尿嘧啶(mU)核苷酸，并且反向引物的5’端为化学磷酸化的。然后这些引物的修饰使得可以使用λ核酸外切酶主要仅对反义链进行受控酶解。所述mU帽保护正义链不被核酸酶酶解，而在反义链5’的PO4促进该酶解。因此，在用λ核酸外切酶孵育后，仅双链的正义链保持完整，现成为单链DNA(ssDNA)。产生的ssDNA然后进行如上所述的PAGE纯化。
本文中所述所有实施例中使用的DNA底物的设计如图2所示。所述DNA底物由来自PhiX的ssDNA的一400个碱基部分组成，具有一50T的5’-前导区。在50T前导区之后退火到该链的是含有3’胆固醇标签的引物以使DNA富集在所述双分子层的表面，并由此提高捕获效率。
从嵌入到1,2-二植烷酰-甘油基-3-磷酸胆碱脂质(DPhPC,Avanti Polar Lipids)双分子层中的单个野生型胞溶素(SEQ ID NO:2)纳米孔获得电测量值。在20μm厚PTFE膜(在常规Delrin室内)中跨～100μm直径的孔洞通过Montal-Mueller技术形成双分子层，隔开两个1mL的缓冲溶液。所有实验在所述缓冲液中进行。使用装配有1440A数字转换器的Axopatch 200B放大器(分子装置)测定单通道电流。将铂电极连接到缓冲溶液，使得顺式隔室(cis-compartment)(其中添加有纳米孔和酶/DNA)连接到Axopatch headstage的接地端(the ground of the Axopatch headstage)，并且反式隔间连接到所述headstage的活性电极(active electrode)。
在缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中在所述双分子层中实现单个野生型胞溶素(SEQ ID NO:2)孔之后，在+120mV下运行一对照实验5分钟。将DNA多核苷酸(SEQ ID NO:13和14)和Hel308 Mbu(SEQID NO:15)添加到50μL的缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中并预孵育5分钟(DNA＝6nM,酶(Hel308 Mbu)＝2μM)。将该预孵育的混合物添加到电生理学室的顺式隔间中的950μL缓冲液(625mM KCl,100mMHepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中以设法引发解旋酶-DNA复合体在所述胞溶素纳米孔中的捕获(得到最终浓度：DNA＝0.3nM,酶(Hel308 Mbu)＝100nM(SEQ ID NO:15))。在+120mV运行另一对照实验5分钟。根据需要通过向顺式隔室中添加NTP(1mM ATP)来引发解旋酶ATP酶活性。在+120mV的恒定电势下进行实验。
结果与讨论
可以观察到WT胞溶素(SEQ ID NO:2)纳米孔插入到了DPhPC双分子层中(图3)。观察到约280pA的稳定开孔电流。但是，当向顺式隔室中添加解旋酶-DNA底物混合物之外，没有观察到DNA捕获事件或解旋酶控制的DNA移动。
实施例3
该实施例说明了使用Hel308解旋酶(Hel308 MBu,SEQ ID NO:15)来控制完整DNA链穿过突变体胞溶素纳米孔(具有突变E84D/E85K的Lys-E84D/E85K,SEQ ID NO:2)的运动。该实施例的一般方法和用到的底物示于图1中并在该图附图标记有描述。
按实施例2中所述获得电测量值。在缓冲条件(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III))下在双分子层中实现单个胞溶素-E84D/E85K(具有突变E84D/E85K的SEQ ID NO:2)孔之后，向顺式隔室中添加MgCl2(10mM)，并在+120mV下运行一对照实验5分钟。将DNA多核苷酸(SEQ ID NO:13和14)和Hel308 Mbu(SEQ ID NO:15)添加到50μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中并预孵育5分钟(DNA＝6nM,酶＝2μM)。将该预孵育的混合物添加到电生理学室的顺式隔间中的950μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中以引发解旋酶-DNA复合体在胞溶素纳米孔中的捕获(得到最终浓度：DNA＝0.3nM,酶＝100nM(SEQ ID NO:15))。在+120mV运行另一对照实验10分钟。根据需要通过向顺式隔室中添加NTP(1mM ATP)来引发解旋酶ATP酶活性。在+120mV或+180mV的恒定电势下进行实验。
结果与讨论
如图1中所示向胞溶素-E84D/E85K(具有突变E84D/E85K的SEQ ID NO:2)中添加解旋酶-DNA底物产生了如图4所示的特征电流模块(在+180mV的施加电势下)。没有结合解旋酶的DNA短暂地与所述纳米孔相互作用产生短期的电流模块(<<1秒)。结合有解旋酶并且具有活性的(即在ATP酶作用下沿着DNA链移动)DNA产生如图4所示电流逐步变化的长特征模块水平。纳米孔中的不同DNA模序产生独特的电流模块水平。
对于给定的底物，我们观察了反映DNA序列的电流转变的特征图(图4中的实施例)。观察到，该事件范围约为25pA(在+180mV的施加电势下)。
实施例4
该实施例说明了使用Hel308解旋酶(Hel308 MBu,SEQ ID NO:15)来控制完整DNA链穿过突变体胞溶素纳米孔(具有突变E92N/E94N/E97N/D121N/D126N的胞溶素-E92N/E94N/E97N/D121N/D126N,SEQ ID NO:2)的运动。该实施例的一般方法和用到的底物示于图1中并在该图附图标记有描述。
按实施例2中所述获得电测量值。在缓冲条件(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III))下在双分子层中实现单个胞溶素-E92N/E94N/E97N/D121N/D126N(具有突变E92N/E94N/E97N/D121N/D126N的SEQ ID NO:2)纳米孔之后，向顺式隔室中添加MgCl2(10mM)，并在+120mV下运行一对照实验5分钟。将DNA多核苷酸(SEQID NO:13和14)和Hel308 Mbu(SEQ ID NO:15)添加到50μL缓冲液(625mM KCl,100mM HepespH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中并预孵育5分钟(DNA＝6nM,酶＝2μM)。将该预孵育的混合物添加到电生理学室的顺式隔间中的950μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mMMgCl2)中以引发解旋酶-DNA复合体在胞溶素纳米孔中的捕获(得到最终浓度：DNA＝0.3nM,酶＝100nM)。在+120mV运行另一对照实验10分钟。根据需要通过向顺式隔室中添加NTP(1mMATP)来引发解旋酶ATP酶活性。在+120mV的恒定电势下进行实验。
结果与讨论
如图1中所示向胞溶素-E92N/E94N/E97N/D121N/D126N(具有突变E92N/E94N/E97N/D121N/D126N的SEQ ID NO:2)中添加解旋酶-DNA底物产生了如图5所示的特征电流模块。没有结合解旋酶的DNA短暂地与所述纳米孔相互作用产生短期的电流模块(<<1秒)。结合有解旋酶并且具有活性的(即在ATP酶作用下沿着DNA链移动)DNA产生如图5所示电流逐步变化的长特征模块水平。纳米孔中的不同DNA模序产生独特的电流模块水平。对于给定的底物，我们观察了反映DNA序列的电流转变的特征图(图5中的实施例)。观察到，该事件范围约为60pA。
实施例5
该实施例说明了使用Hel308解旋酶(Hel308 MBu,SEQ ID NO:15)来控制完整DNA链穿过突变体胞溶素纳米孔(胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A,具有突变E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2)的运动。该实施例的一般方法和用到的底物示于图1中并在该图附图标记有描述。
按实施例2中所述获得电测量值。在缓冲条件(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III))下在双分子层中实现单个胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A(具有突变E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2)纳米孔之后，向顺式隔室中添加MgCl2(10mM)，并在+120mV下运行一对照实验5分钟。6个突变中，前5个(E84Q/E85K/E92Q/E97S/D126G)是在根据本发明的44-126的区域中。最后一个(E167A)是在上述区域之外的另一突变。将DNA多核苷酸(SEQ ID NO:13和14)和Hel308 Mbu(SEQ ID NO:15)添加到50μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中并预孵育5分钟(DNA＝12nM,酶＝2μM)。将该预孵育的混合物添加到电生理学室的顺式隔间中的950μL缓冲液(625mM KCl,100mM Hepes pH8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),10mM MgCl2)中以引发解旋酶-DNA复合体在胞溶素纳米孔中的捕获(得到最终浓度：DNA＝0.6nM,酶＝100nM)。在+120mV运行另一对照实验10分钟。根据需要通过向顺式隔室中添加NTP(1mM ATP)来引发解旋酶ATP酶活性。在+120或+180mV的恒定电势下进行实验。
结果与讨论
如图1中所示向胞溶素纳米孔胞溶素-E84Q/E85K/E92Q/E97S/D126G/E167A(具有突变E84Q/E85K/E92Q/E97S/D126G/E167A的SEQ ID NO:2)中添加解旋酶-DNA底物产生了如图6所示的特征电流模块(在+180mV的施加电势下)。没有结合解旋酶的DNA短暂地与所述纳米孔相互作用产生短期的电流模块(<<1秒)。结合有解旋酶并且具有活性的(即在ATP酶作用下沿着DNA链移动)DNA产生如图6所示电流逐步变化的长特征模块水平。纳米孔中的不同DNA模序产生独特的电流模块水平。对于给定的底物，我们观察了反映DNA序列的电流转变的特征图(图6中的实施例)。观察到，该事件范围约为30pA(在+180mV的施加电势下)。
实施例6
该实施例说明了使用Hel308解旋酶(Hel308 MBu,SEQ ID NO:15)来控制完整DNA链穿过许多不同突变体胞溶素纳米孔(对于所测试的突变体孔的列表见表4)的运动。该实施例的一般方法和用到的底物示于图1中并在该图附图标记有描述。
按实施例2中所述获得电测量值。在缓冲条件(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III))下在双分子层中实现单个胞溶素突变体孔(见下文所测试的纳米孔列表)之后，向顺式隔室中添加MgCl2(10mM)，并在+120mV下运行一对照实验5分钟。将DNA多核苷酸(SEQ ID NO:13和14)和Hel308 Mbu(SEQ ID NO:15)添加到50μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH8.0,10mM MgCl2)中并预孵育5分钟(DNA＝12,6或3nM,酶＝2μM)。将该预孵育的混合物添加到电生理学室的顺式隔间中的950μL缓冲液(625mM KCl,100mM Hepes pH 8.0,75mM亚铁氰化钾(II),25mM铁氰化钾(III),pH 8.0,10mM MgCl2)中以引发解旋酶-DNA复合体在胞溶素纳米孔中的捕获(得到最终浓度：DNA＝0.6,0.3或0.15nM,酶＝100nM)。在+120mV运行另一对照实验10分钟。根据需要通过向顺式隔室中添加NTP(1mM ATP)来引发解旋酶ATP酶活性。在+120或+180mV的恒定电势下进行实验。
结果与讨论
如图1中所示向单个胞溶素纳米孔(见下文表4中所列孔)中添加解旋酶-DNA底物(EQ ID NO:13和14)产生了如图7-12所示的特征电流模块(在+120或+180mV的施加电势下)。没有结合解旋酶的DNA短暂地与所述纳米孔相互作用产生短期的电流模块(<<1秒)。对于多个所测试的胞溶素突变体，结合有解旋酶并且具有活性的(即在ATP酶作用下沿着DNA链移动)DNA产生如图7-12所示电流逐步变化的长特征模块水平。纳米孔中的不同DNA模序产生独特的电流模块水平。
表4
实施例7
该实施例描述了一种利用大肠杆菌表达来合成突变体胞溶素纳米孔的方法。
材料和方法
用含有构造Strep-TrxEco-TEV-胞溶素的质粒转化大肠杆菌Rosetta2(DE3)pLysS细胞，通过添加0.2mM IPTG并在18℃放置过夜来引发表达。将所述细胞在400rpm下30分钟以收集沉淀。将细胞沉淀重新悬浮于50mM Tris 300mM NaCl 0.1μl/ml核酸酶(benzonase)10μl/ml Calbiochem系列V蛋白酶抑制剂中的1X的BugBuster中并在4℃放置4小时。将裂解物(lysate)在20000rpm下自旋30分钟并通过0.2μm的过滤器。
将过滤的裂解物上样到StrepTrap柱上，在100mM Tris 300mM NaCl10mM脱硫生物素(dethiobiotin)pH 8.0下进行洗脱。通过用链球菌(Strep)标记的TEV蛋白酶(1:20w/w)在4℃孵育过夜来除去Strep-TrxEco-TEV标签。通过用链球菌珠(strep bead)孵育来除去任何未裂解的蛋白质、裂解的标签和TEV蛋白酶。通过离心除去所述链球菌珠并向上清液中添加鞘磷脂(1mg/ml)，然后在37℃放置过夜。
序列表
<110> 牛津纳米孔技术公司
<120> 突变胞溶素孔
<130> N. 116729A
<150> US 61/622,174
<151> 2012-04-10
<160> 19
<170> PatentIn version 3.5
<210> 1
<211> 897
<212> DNA
<213> 赤子爱胜蚓
<400> 1
atgagtgcga aggctgctga aggttatgaa caaatcgaag ttgatgtggt tgctgtgtgg 60
aaggaaggtt atgtgtatga aaatcgtggt agtacctccg tggatcaaaa aattaccatc 120
acgaaaggca tgaagaacgt taatagcgaa acccgtacgg tcaccgcgac gcattctatt 180
ggcagtacca tctccacggg tgacgccttt gaaatcggct ccgtggaagt ttcatattcg 240
catagccacg aagaatcaca agtttcgatg accgaaacgg aagtctacga atcaaaagtg 300
attgaacaca ccattacgat cccgccgacc tcgaagttca cgcgctggca gctgaacgca 360
gatgtcggcg gtgctgacat tgaatatatg tacctgatcg atgaagttac cccgattggc 420
ggtacgcaga gtattccgca agtgatcacc tcccgtgcaa aaattatcgt tggtcgccag 480
attatcctgg gcaagaccga aattcgtatc aaacatgctg aacgcaagga atatatgacc 540
gtggttagcc gtaaatcttg gccggcggcc acgctgggtc acagtaaact gtttaagttc 600
gtgctgtacg aagattgggg cggttttcgc atcaaaaccc tgaatacgat gtattctggt 660
tatgaatacg cgtatagctc tgaccagggc ggtatctact tcgatcaagg caccgacaac 720
ccgaaacagc gttgggccat taataagagc ctgccgctgc gccatggtga tgtcgtgacc 780
tttatgaaca aatacttcac gcgttctggt ctgtgctatg atgacggccc ggcgaccaat 840
gtgtattgtc tggataaacg cgaagacaag tggattctgg aagttgtcgg ctaatga 897
<210> 2
<211> 297
<212> PRT
<213> 赤子爱胜蚓
<400> 2
Met Ser Ala Lys Ala Ala Glu Gly Tyr Glu Gln Ile Glu Val Asp Val
1 5 10 15
Val Ala Val Trp Lys Glu Gly Tyr Val Tyr Glu Asn Arg Gly Ser Thr
20 25 30
Ser Val Asp Gln Lys Ile Thr Ile Thr Lys Gly Met Lys Asn Val Asn
35 40 45
Ser Glu Thr Arg Thr Val Thr Ala Thr His Ser Ile Gly Ser Thr Ile
50 55 60
Ser Thr Gly Asp Ala Phe Glu Ile Gly Ser Val Glu Val Ser Tyr Ser
65 70 75 80
His Ser His Glu Glu Ser Gln Val Ser Met Thr Glu Thr Glu Val Tyr
85 90 95
Glu Ser Lys Val Ile Glu His Thr Ile Thr Ile Pro Pro Thr Ser Lys
100 105 110
Phe Thr Arg Trp Gln Leu Asn Ala Asp Val Gly Gly Ala Asp Ile Glu
115 120 125
Tyr Met Tyr Leu Ile Asp Glu Val Thr Pro Ile Gly Gly Thr Gln Ser
130 135 140
Ile Pro Gln Val Ile Thr Ser Arg Ala Lys Ile Ile Val Gly Arg Gln
145 150 155 160
Ile Ile Leu Gly Lys Thr Glu Ile Arg Ile Lys His Ala Glu Arg Lys
165 170 175
Glu Tyr Met Thr Val Val Ser Arg Lys Ser Trp Pro Ala Ala Thr Leu
180 185 190
Gly His Ser Lys Leu Phe Lys Phe Val Leu Tyr Glu Asp Trp Gly Gly
195 200 205
Phe Arg Ile Lys Thr Leu Asn Thr Met Tyr Ser Gly Tyr Glu Tyr Ala
210 215 220
Tyr Ser Ser Asp Gln Gly Gly Ile Tyr Phe Asp Gln Gly Thr Asp Asn
225 230 235 240
Pro Lys Gln Arg Trp Ala Ile Asn Lys Ser Leu Pro Leu Arg His Gly
245 250 255
Asp Val Val Thr Phe Met Asn Lys Tyr Phe Thr Arg Ser Gly Leu Cys
260 265 270
Tyr Asp Asp Gly Pro Ala Thr Asn Val Tyr Cys Leu Asp Lys Arg Glu
275 280 285
Asp Lys Trp Ile Leu Glu Val Val Gly
290 295
<210> 3
<211> 1830
<212> DNA
<213> 噬菌体 phi AR29
<400> 3
atgaaacaca tgccgcgtaa aatgtatagc tgcgcgtttg aaaccacgac caaagtggaa 60
gattgtcgcg tttgggccta tggctacatg aacatcgaag atcattctga atacaaaatc 120
ggtaacagtc tggatgaatt tatggcatgg gtgctgaaag ttcaggcgga tctgtacttc 180
cacaacctga aatttgatgg cgcattcatt atcaactggc tggaacgtaa tggctttaaa 240
tggagcgcgg atggtctgcc gaacacgtat aataccatta tctctcgtat gggccagtgg 300
tatatgattg atatctgcct gggctacaaa ggtaaacgca aaattcatac cgtgatctat 360
gatagcctga aaaaactgcc gtttccggtg aagaaaattg cgaaagattt caaactgacg 420
gttctgaaag gcgatattga ttatcacaaa gaacgtccgg ttggttacaa aatcaccccg 480
gaagaatacg catacatcaa aaacgatatc cagatcatcg cagaagcgct gctgattcag 540
tttaaacagg gcctggatcg catgaccgcg ggcagtgata gcctgaaagg tttcaaagat 600
atcatcacga ccaaaaaatt caaaaaagtg ttcccgacgc tgagcctggg tctggataaa 660
gaagttcgtt atgcctaccg cggcggtttt acctggctga acgatcgttt caaagaaaaa 720
gaaattggcg agggtatggt gtttgatgtt aatagtctgt atccggcaca gatgtacagc 780
cgcctgctgc cgtatggcga accgatcgtg ttcgagggta aatatgtttg ggatgaagat 840
tacccgctgc atattcagca catccgttgt gaatttgaac tgaaagaagg ctatattccg 900
accattcaga tcaaacgtag tcgcttctat aagggtaacg aatacctgaa aagctctggc 960
ggtgaaatcg cggatctgtg gctgagtaac gtggatctgg aactgatgaa agaacactac 1020
gatctgtaca acgttgaata catcagcggc ctgaaattta aagccacgac cggtctgttc 1080
aaagatttca tcgataaatg gacctacatc aaaacgacct ctgaaggcgc gattaaacag 1140
ctggccaaac tgatgctgaa cagcctgtat ggcaaattcg cctctaatcc ggatgtgacc 1200
ggtaaagttc cgtacctgaa agaaaatggc gcactgggtt ttcgcctggg cgaagaagaa 1260
acgaaagatc cggtgtatac cccgatgggt gttttcatta cggcctgggc acgttacacg 1320
accatcaccg cggcccaggc atgctatgat cgcattatct actgtgatac cgattctatt 1380
catctgacgg gcaccgaaat cccggatgtg attaaagata tcgttgatcc gaaaaaactg 1440
ggttattggg cccacgaaag tacgtttaaa cgtgcaaaat acctgcgcca gaaaacctac 1500
atccaggata tctacatgaa agaagtggat ggcaaactgg ttgaaggttc tccggatgat 1560
tacaccgata tcaaattcag tgtgaaatgc gccggcatga cggataaaat caaaaaagaa 1620
gtgaccttcg aaaacttcaa agttggtttc agccgcaaaa tgaaaccgaa accggtgcag 1680
gttccgggcg gtgtggttct ggtggatgat acgtttacca ttaaatctgg cggtagtgcg 1740
tggagccatc cgcagttcga aaaaggcggt ggctctggtg gcggttctgg cggtagtgcc 1800
tggagccacc cgcagtttga aaaataataa 1830
<210> 4
<211> 608
<212> PRT
<213> 噬菌体phi AR29
<400> 4
Met Lys His Met Pro Arg Lys Met Tyr Ser Cys Ala Phe Glu Thr Thr
1 5 10 15
Thr Lys Val Glu Asp Cys Arg Val Trp Ala Tyr Gly Tyr Met Asn Ile
20 25 30
Glu Asp His Ser Glu Tyr Lys Ile Gly Asn Ser Leu Asp Glu Phe Met
35 40 45
Ala Trp Val Leu Lys Val Gln Ala Asp Leu Tyr Phe His Asn Leu Lys
50 55 60
Phe Asp Gly Ala Phe Ile Ile Asn Trp Leu Glu Arg Asn Gly Phe Lys
65 70 75 80
Trp Ser Ala Asp Gly Leu Pro Asn Thr Tyr Asn Thr Ile Ile Ser Arg
85 90 95
Met Gly Gln Trp Tyr Met Ile Asp Ile Cys Leu Gly Tyr Lys Gly Lys
100 105 110
Arg Lys Ile His Thr Val Ile Tyr Asp Ser Leu Lys Lys Leu Pro Phe
115 120 125
Pro Val Lys Lys Ile Ala Lys Asp Phe Lys Leu Thr Val Leu Lys Gly
130 135 140
Asp Ile Asp Tyr His Lys Glu Arg Pro Val Gly Tyr Lys Ile Thr Pro
145 150 155 160
Glu Glu Tyr Ala Tyr Ile Lys Asn Asp Ile Gln Ile Ile Ala Glu Ala
165 170 175
Leu Leu Ile Gln Phe Lys Gln Gly Leu Asp Arg Met Thr Ala Gly Ser
180 185 190
Asp Ser Leu Lys Gly Phe Lys Asp Ile Ile Thr Thr Lys Lys Phe Lys
195 200 205
Lys Val Phe Pro Thr Leu Ser Leu Gly Leu Asp Lys Glu Val Arg Tyr
210 215 220
Ala Tyr Arg Gly Gly Phe Thr Trp Leu Asn Asp Arg Phe Lys Glu Lys
225 230 235 240
Glu Ile Gly Glu Gly Met Val Phe Asp Val Asn Ser Leu Tyr Pro Ala
245 250 255
Gln Met Tyr Ser Arg Leu Leu Pro Tyr Gly Glu Pro Ile Val Phe Glu
260 265 270
Gly Lys Tyr Val Trp Asp Glu Asp Tyr Pro Leu His Ile Gln His Ile
275 280 285
Arg Cys Glu Phe Glu Leu Lys Glu Gly Tyr Ile Pro Thr Ile Gln Ile
290 295 300
Lys Arg Ser Arg Phe Tyr Lys Gly Asn Glu Tyr Leu Lys Ser Ser Gly
305 310 315 320
Gly Glu Ile Ala Asp Leu Trp Leu Ser Asn Val Asp Leu Glu Leu Met
325 330 335
Lys Glu His Tyr Asp Leu Tyr Asn Val Glu Tyr Ile Ser Gly Leu Lys
340 345 350
Phe Lys Ala Thr Thr Gly Leu Phe Lys Asp Phe Ile Asp Lys Trp Thr
355 360 365
Tyr Ile Lys Thr Thr Ser Glu Gly Ala Ile Lys Gln Leu Ala Lys Leu
370 375 380
Met Leu Asn Ser Leu Tyr Gly Lys Phe Ala Ser Asn Pro Asp Val Thr
385 390 395 400
Gly Lys Val Pro Tyr Leu Lys Glu Asn Gly Ala Leu Gly Phe Arg Leu
405 410 415
Gly Glu Glu Glu Thr Lys Asp Pro Val Tyr Thr Pro Met Gly Val Phe
420 425 430
Ile Thr Ala Trp Ala Arg Tyr Thr Thr Ile Thr Ala Ala Gln Ala Cys
435 440 445
Tyr Asp Arg Ile Ile Tyr Cys Asp Thr Asp Ser Ile His Leu Thr Gly
450 455 460
Thr Glu Ile Pro Asp Val Ile Lys Asp Ile Val Asp Pro Lys Lys Leu
465 470 475 480
Gly Tyr Trp Ala His Glu Ser Thr Phe Lys Arg Ala Lys Tyr Leu Arg
485 490 495
Gln Lys Thr Tyr Ile Gln Asp Ile Tyr Met Lys Glu Val Asp Gly Lys
500 505 510
Leu Val Glu Gly Ser Pro Asp Asp Tyr Thr Asp Ile Lys Phe Ser Val
515 520 525
Lys Cys Ala Gly Met Thr Asp Lys Ile Lys Lys Glu Val Thr Phe Glu
530 535 540
Asn Phe Lys Val Gly Phe Ser Arg Lys Met Lys Pro Lys Pro Val Gln
545 550 555 560
Val Pro Gly Gly Val Val Leu Val Asp Asp Thr Phe Thr Ile Lys Ser
565 570 575
Gly Gly Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser
580 585 590
Gly Gly Gly Ser Gly Gly Ser Ala Trp Ser His Pro Gln Phe Glu Lys
595 600 605
<210> 5
<211> 1390
<212> DNA
<213> 大肠杆菌
<400> 5
atgatgaacg atggcaaaca gcagagcacc ttcctgtttc atgattatga aaccttcggt 60
acccatccgg ccctggatcg tccggcgcag tttgcggcca ttcgcaccga tagcgaattc 120
aatgtgattg gcgaaccgga agtgttttat tgcaaaccgg ccgatgatta tctgccgcag 180
ccgggtgcgg tgctgattac cggtattacc ccgcaggaag cgcgcgcgaa aggtgaaaac 240
gaagcggcgt ttgccgcgcg cattcatagc ctgtttaccg tgccgaaaac ctgcattctg 300
ggctataaca atgtgcgctt cgatgatgaa gttacccgta atatctttta tcgtaacttt 360
tatgatccgt atgcgtggag ctggcagcat gataacagcc gttgggatct gctggatgtg 420
atgcgcgcgt gctatgcgct gcgcccggaa ggcattaatt ggccggaaaa cgatgatggc 480
ctgccgagct ttcgtctgga acatctgacc aaagccaacg gcattgaaca tagcaatgcc 540
catgatgcga tggccgatgt ttatgcgacc attgcgatgg cgaaactggt taaaacccgt 600
cagccgcgcc tgtttgatta tctgtttacc caccgtaaca aacacaaact gatggcgctg 660
attgatgttc cgcagatgaa accgctggtg catgtgagcg gcatgtttgg cgcctggcgc 720
ggcaacacca gctgggtggc cccgctggcc tggcacccgg aaaatcgtaa cgccgtgatt 780
atggttgatc tggccggtga tattagcccg ctgctggaac tggatagcga taccctgcgt 840
gaacgcctgt ataccgccaa aaccgatctg ggcgataatg ccgccgtgcc ggtgaaactg 900
gttcacatta acaaatgccc ggtgctggcc caggcgaaca ccctgcgccc ggaagatgcg 960
gatcgtctgg gtattaatcg ccagcattgt ctggataatc tgaaaatcct gcgtgaaaac 1020
ccgcaggtgc gtgaaaaagt ggtggcgatc ttcgcggaag cggaaccgtt caccccgagc 1080
gataacgtgg atgcgcagct gtataacggc ttctttagcg atgccgatcg cgcggcgatg 1140
aaaatcgttc tggaaaccga accgcgcaat ctgccggcgc tggatattac ctttgttgat 1200
aaacgtattg aaaaactgct gtttaattat cgtgcgcgca attttccggg taccctggat 1260
tatgccgaac agcagcgttg gctggaacat cgtcgtcagg ttttcacccc ggaatttctg 1320
cagggttatg cggatgaact gcagatgctg gttcagcagt atgccgatga taaagaaaaa 1380
gtggcgctgc 1390
<210> 6
<211> 485
<212> PRT
<213> 大肠杆菌
<400> 6
Met Met Asn Asp Gly Lys Gln Gln Ser Thr Phe Leu Phe His Asp Tyr
1 5 10 15
Glu Thr Phe Gly Thr His Pro Ala Leu Asp Arg Pro Ala Gln Phe Ala
20 25 30
Ala Ile Arg Thr Asp Ser Glu Phe Asn Val Ile Gly Glu Pro Glu Val
35 40 45
Phe Tyr Cys Lys Pro Ala Asp Asp Tyr Leu Pro Gln Pro Gly Ala Val
50 55 60
Leu Ile Thr Gly Ile Thr Pro Gln Glu Ala Arg Ala Lys Gly Glu Asn
65 70 75 80
Glu Ala Ala Phe Ala Ala Arg Ile His Ser Leu Phe Thr Val Pro Lys
85 90 95
Thr Cys Ile Leu Gly Tyr Asn Asn Val Arg Phe Asp Asp Glu Val Thr
100 105 110
Arg Asn Ile Phe Tyr Arg Asn Phe Tyr Asp Pro Tyr Ala Trp Ser Trp
115 120 125
Gln His Asp Asn Ser Arg Trp Asp Leu Leu Asp Val Met Arg Ala Cys
130 135 140
Tyr Ala Leu Arg Pro Glu Gly Ile Asn Trp Pro Glu Asn Asp Asp Gly
145 150 155 160
Leu Pro Ser Phe Arg Leu Glu His Leu Thr Lys Ala Asn Gly Ile Glu
165 170 175
His Ser Asn Ala His Asp Ala Met Ala Asp Val Tyr Ala Thr Ile Ala
180 185 190
Met Ala Lys Leu Val Lys Thr Arg Gln Pro Arg Leu Phe Asp Tyr Leu
195 200 205
Phe Thr His Arg Asn Lys His Lys Leu Met Ala Leu Ile Asp Val Pro
210 215 220
Gln Met Lys Pro Leu Val His Val Ser Gly Met Phe Gly Ala Trp Arg
225 230 235 240
Gly Asn Thr Ser Trp Val Ala Pro Leu Ala Trp His Pro Glu Asn Arg
245 250 255
Asn Ala Val Ile Met Val Asp Leu Ala Gly Asp Ile Ser Pro Leu Leu
260 265 270
Glu Leu Asp Ser Asp Thr Leu Arg Glu Arg Leu Tyr Thr Ala Lys Thr
275 280 285
Asp Leu Gly Asp Asn Ala Ala Val Pro Val Lys Leu Val His Ile Asn
290 295 300
Lys Cys Pro Val Leu Ala Gln Ala Asn Thr Leu Arg Pro Glu Asp Ala
305 310 315 320
Asp Arg Leu Gly Ile Asn Arg Gln His Cys Leu Asp Asn Leu Lys Ile
325 330 335
Leu Arg Glu Asn Pro Gln Val Arg Glu Lys Val Val Ala Ile Phe Ala
340 345 350
Glu Ala Glu Pro Phe Thr Pro Ser Asp Asn Val Asp Ala Gln Leu Tyr
355 360 365
Asn Gly Phe Phe Ser Asp Ala Asp Arg Ala Ala Met Lys Ile Val Leu
370 375 380
Glu Thr Glu Pro Arg Asn Leu Pro Ala Leu Asp Ile Thr Phe Val Asp
385 390 395 400
Lys Arg Ile Glu Lys Leu Leu Phe Asn Tyr Arg Ala Arg Asn Phe Pro
405 410 415
Gly Thr Leu Asp Tyr Ala Glu Gln Gln Arg Trp Leu Glu His Arg Arg
420 425 430
Gln Val Phe Thr Pro Glu Phe Leu Gln Gly Tyr Ala Asp Glu Leu Gln
435 440 445
Met Leu Val Gln Gln Tyr Ala Asp Asp Lys Glu Lys Val Ala Leu Leu
450 455 460
Lys Ala Leu Trp Gln Tyr Ala Glu Glu Ile Val Ser Gly Ser Gly His
465 470 475 480
His His His His His
485
<210> 7
<211> 804
<212> DNA
<213> 大肠杆菌
<400> 7
atgaaatttg tctcttttaa tatcaacggc ctgcgcgcca gacctcacca gcttgaagcc 60
atcgtcgaaa agcaccaacc ggatgtgatt ggcctgcagg agacaaaagt tcatgacgat 120
atgtttccgc tcgaagaggt ggcgaagctc ggctacaacg tgttttatca cgggcagaaa 180
ggccattatg gcgtggcgct gctgaccaaa gagacgccga ttgccgtgcg tcgcggcttt 240
cccggtgacg acgaagaggc gcagcggcgg attattatgg cggaaatccc ctcactgctg 300
ggtaatgtca ccgtgatcaa cggttacttc ccgcagggtg aaagccgcga ccatccgata 360
aaattcccgg caaaagcgca gttttatcag aatctgcaaa actacctgga aaccgaactc 420
aaacgtgata atccggtact gattatgggc gatatgaata tcagccctac agatctggat 480
atcggcattg gcgaagaaaa ccgtaagcgc tggctgcgta ccggtaaatg ctctttcctg 540
ccggaagagc gcgaatggat ggacaggctg atgagctggg ggttggtcga taccttccgc 600
catgcgaatc cgcaaacagc agatcgtttc tcatggtttg attaccgctc aaaaggtttt 660
gacgataacc gtggtctgcg catcgacctg ctgctcgcca gccaaccgct ggcagaatgt 720
tgcgtagaaa ccggcatcga ctatgaaatc cgcagcatgg aaaaaccgtc cgatcacgcc 780
cccgtctggg cgaccttccg ccgc 804
<210> 8
<211> 268
<212> PRT
<213> 大肠杆菌
<400> 8
Met Lys Phe Val Ser Phe Asn Ile Asn Gly Leu Arg Ala Arg Pro His
1 5 10 15
Gln Leu Glu Ala Ile Val Glu Lys His Gln Pro Asp Val Ile Gly Leu
20 25 30
Gln Glu Thr Lys Val His Asp Asp Met Phe Pro Leu Glu Glu Val Ala
35 40 45
Lys Leu Gly Tyr Asn Val Phe Tyr His Gly Gln Lys Gly His Tyr Gly
50 55 60
Val Ala Leu Leu Thr Lys Glu Thr Pro Ile Ala Val Arg Arg Gly Phe
65 70 75 80
Pro Gly Asp Asp Glu Glu Ala Gln Arg Arg Ile Ile Met Ala Glu Ile
85 90 95
Pro Ser Leu Leu Gly Asn Val Thr Val Ile Asn Gly Tyr Phe Pro Gln
100 105 110
Gly Glu Ser Arg Asp His Pro Ile Lys Phe Pro Ala Lys Ala Gln Phe
115 120 125
Tyr Gln Asn Leu Gln Asn Tyr Leu Glu Thr Glu Leu Lys Arg Asp Asn
130 135 140
Pro Val Leu Ile Met Gly Asp Met Asn Ile Ser Pro Thr Asp Leu Asp
145 150 155 160
Ile Gly Ile Gly Glu Glu Asn Arg Lys Arg Trp Leu Arg Thr Gly Lys
165 170 175
Cys Ser Phe Leu Pro Glu Glu Arg Glu Trp Met Asp Arg Leu Met Ser
180 185 190
Trp Gly Leu Val Asp Thr Phe Arg His Ala Asn Pro Gln Thr Ala Asp
195 200 205
Arg Phe Ser Trp Phe Asp Tyr Arg Ser Lys Gly Phe Asp Asp Asn Arg
210 215 220
Gly Leu Arg Ile Asp Leu Leu Leu Ala Ser Gln Pro Leu Ala Glu Cys
225 230 235 240
Cys Val Glu Thr Gly Ile Asp Tyr Glu Ile Arg Ser Met Glu Lys Pro
245 250 255
Ser Asp His Ala Pro Val Trp Ala Thr Phe Arg Arg
260 265
<210> 9
<211> 1275
<212> DNA
<213> 嗜热栖热菌属（Thermus thermophilus）
<400> 9
atgtttcgtc gtaaagaaga tctggatccg ccgctggcac tgctgccgct gaaaggcctg 60
cgcgaagccg ccgcactgct ggaagaagcg ctgcgtcaag gtaaacgcat tcgtgttcac 120
ggcgactatg atgcggatgg cctgaccggc accgcgatcc tggttcgtgg tctggccgcc 180
ctgggtgcgg atgttcatcc gtttatcccg caccgcctgg aagaaggcta tggtgtcctg 240
atggaacgcg tcccggaaca tctggaagcc tcggacctgt ttctgaccgt tgactgcggc 300
attaccaacc atgcggaact gcgcgaactg ctggaaaatg gcgtggaagt cattgttacc 360
gatcatcata cgccgggcaa aacgccgccg ccgggtctgg tcgtgcatcc ggcgctgacg 420
ccggatctga aagaaaaacc gaccggcgca ggcgtggcgt ttctgctgct gtgggcactg 480
catgaacgcc tgggcctgcc gccgccgctg gaatacgcgg acctggcagc cgttggcacc 540
attgccgacg ttgccccgct gtggggttgg aatcgtgcac tggtgaaaga aggtctggca 600
cgcatcccgg cttcatcttg ggtgggcctg cgtctgctgg ctgaagccgt gggctatacc 660
ggcaaagcgg tcgaagtcgc tttccgcatc gcgccgcgca tcaatgcggc ttcccgcctg 720
ggcgaagcgg aaaaagccct gcgcctgctg ctgacggatg atgcggcaga agctcaggcg 780
ctggtcggcg aactgcaccg tctgaacgcc cgtcgtcaga ccctggaaga agcgatgctg 840
cgcaaactgc tgccgcaggc cgacccggaa gcgaaagcca tcgttctgct ggacccggaa 900
ggccatccgg gtgttatggg tattgtggcc tctcgcatcc tggaagcgac cctgcgcccg 960
gtctttctgg tggcccaggg caaaggcacc gtgcgttcgc tggctccgat ttccgccgtc 1020
gaagcactgc gcagcgcgga agatctgctg ctgcgttatg gtggtcataa agaagcggcg 1080
ggtttcgcaa tggatgaagc gctgtttccg gcgttcaaag cacgcgttga agcgtatgcc 1140
gcacgtttcc cggatccggt tcgtgaagtg gcactgctgg atctgctgcc ggaaccgggc 1200
ctgctgccgc aggtgttccg tgaactggca ctgctggaac cgtatggtga aggtaacccg 1260
gaaccgctgt tcctg 1275
<210> 10
<211> 425
<212> PRT
<213> 嗜热栖热菌属
<400> 10
Met Phe Arg Arg Lys Glu Asp Leu Asp Pro Pro Leu Ala Leu Leu Pro
1 5 10 15
Leu Lys Gly Leu Arg Glu Ala Ala Ala Leu Leu Glu Glu Ala Leu Arg
20 25 30
Gln Gly Lys Arg Ile Arg Val His Gly Asp Tyr Asp Ala Asp Gly Leu
35 40 45
Thr Gly Thr Ala Ile Leu Val Arg Gly Leu Ala Ala Leu Gly Ala Asp
50 55 60
Val His Pro Phe Ile Pro His Arg Leu Glu Glu Gly Tyr Gly Val Leu
65 70 75 80
Met Glu Arg Val Pro Glu His Leu Glu Ala Ser Asp Leu Phe Leu Thr
85 90 95
Val Asp Cys Gly Ile Thr Asn His Ala Glu Leu Arg Glu Leu Leu Glu
100 105 110
Asn Gly Val Glu Val Ile Val Thr Asp His His Thr Pro Gly Lys Thr
115 120 125
Pro Pro Pro Gly Leu Val Val His Pro Ala Leu Thr Pro Asp Leu Lys
130 135 140
Glu Lys Pro Thr Gly Ala Gly Val Ala Phe Leu Leu Leu Trp Ala Leu
145 150 155 160
His Glu Arg Leu Gly Leu Pro Pro Pro Leu Glu Tyr Ala Asp Leu Ala
165 170 175
Ala Val Gly Thr Ile Ala Asp Val Ala Pro Leu Trp Gly Trp Asn Arg
180 185 190
Ala Leu Val Lys Glu Gly Leu Ala Arg Ile Pro Ala Ser Ser Trp Val
195 200 205
Gly Leu Arg Leu Leu Ala Glu Ala Val Gly Tyr Thr Gly Lys Ala Val
210 215 220
Glu Val Ala Phe Arg Ile Ala Pro Arg Ile Asn Ala Ala Ser Arg Leu
225 230 235 240
Gly Glu Ala Glu Lys Ala Leu Arg Leu Leu Leu Thr Asp Asp Ala Ala
245 250 255
Glu Ala Gln Ala Leu Val Gly Glu Leu His Arg Leu Asn Ala Arg Arg
260 265 270
Gln Thr Leu Glu Glu Ala Met Leu Arg Lys Leu Leu Pro Gln Ala Asp
275 280 285
Pro Glu Ala Lys Ala Ile Val Leu Leu Asp Pro Glu Gly His Pro Gly
290 295 300
Val Met Gly Ile Val Ala Ser Arg Ile Leu Glu Ala Thr Leu Arg Pro
305 310 315 320
Val Phe Leu Val Ala Gln Gly Lys Gly Thr Val Arg Ser Leu Ala Pro
325 330 335
Ile Ser Ala Val Glu Ala Leu Arg Ser Ala Glu Asp Leu Leu Leu Arg
340 345 350
Tyr Gly Gly His Lys Glu Ala Ala Gly Phe Ala Met Asp Glu Ala Leu
355 360 365
Phe Pro Ala Phe Lys Ala Arg Val Glu Ala Tyr Ala Ala Arg Phe Pro
370 375 380
Asp Pro Val Arg Glu Val Ala Leu Leu Asp Leu Leu Pro Glu Pro Gly
385 390 395 400
Leu Leu Pro Gln Val Phe Arg Glu Leu Ala Leu Leu Glu Pro Tyr Gly
405 410 415
Glu Gly Asn Pro Glu Pro Leu Phe Leu
420 425
<210> 11
<211> 738
<212> DNA
<213> 噬菌体λ
<400> 11
tccggaagcg gctctggtag tggttctggc atgacaccgg acattatcct gcagcgtacc 60
gggatcgatg tgagagctgt cgaacagggg gatgatgcgt ggcacaaatt acggctcggc 120
gtcatcaccg cttcagaagt tcacaacgtg atagcaaaac cccgctccgg aaagaagtgg 180
cctgacatga aaatgtccta cttccacacc ctgcttgctg aggtttgcac cggtgtggct 240
ccggaagtta acgctaaagc actggcctgg ggaaaacagt acgagaacga cgccagaacc 300
ctgtttgaat tcacttccgg cgtgaatgtt actgaatccc cgatcatcta tcgcgacgaa 360
agtatgcgta ccgcctgctc tcccgatggt ttatgcagtg acggcaacgg ccttgaactg 420
aaatgcccgt ttacctcccg ggatttcatg aagttccggc tcggtggttt cgaggccata 480
aagtcagctt acatggccca ggtgcagtac agcatgtggg tgacgcgaaa aaatgcctgg 540
tactttgcca actatgaccc gcgtatgaag cgtgaaggcc tgcattatgt cgtgattgag 600
cgggatgaaa agtacatggc gagttttgac gagatcgtgc cggagttcat cgaaaaaatg 660
gacgaggcac tggctgaaat tggttttgta tttggggagc aatggcgatc tggctctggt 720
tccggcagcg gttccgga 738
<210> 12
<211> 226
<212> PRT
<213> 噬菌体λ
<400> 12
Met Thr Pro Asp Ile Ile Leu Gln Arg Thr Gly Ile Asp Val Arg Ala
1 5 10 15
Val Glu Gln Gly Asp Asp Ala Trp His Lys Leu Arg Leu Gly Val Ile
20 25 30
Thr Ala Ser Glu Val His Asn Val Ile Ala Lys Pro Arg Ser Gly Lys
35 40 45
Lys Trp Pro Asp Met Lys Met Ser Tyr Phe His Thr Leu Leu Ala Glu
50 55 60
Val Cys Thr Gly Val Ala Pro Glu Val Asn Ala Lys Ala Leu Ala Trp
65 70 75 80
Gly Lys Gln Tyr Glu Asn Asp Ala Arg Thr Leu Phe Glu Phe Thr Ser
85 90 95
Gly Val Asn Val Thr Glu Ser Pro Ile Ile Tyr Arg Asp Glu Ser Met
100 105 110
Arg Thr Ala Cys Ser Pro Asp Gly Leu Cys Ser Asp Gly Asn Gly Leu
115 120 125
Glu Leu Lys Cys Pro Phe Thr Ser Arg Asp Phe Met Lys Phe Arg Leu
130 135 140
Gly Gly Phe Glu Ala Ile Lys Ser Ala Tyr Met Ala Gln Val Gln Tyr
145 150 155 160
Ser Met Trp Val Thr Arg Lys Asn Ala Trp Tyr Phe Ala Asn Tyr Asp
165 170 175
Pro Arg Met Lys Arg Glu Gly Leu His Tyr Val Val Ile Glu Arg Asp
180 185 190
Glu Lys Tyr Met Ala Ser Phe Asp Glu Ile Val Pro Glu Phe Ile Glu
195 200 205
Lys Met Asp Glu Ala Leu Ala Glu Ile Gly Phe Val Phe Gly Glu Gln
210 215 220
Trp Arg
225
<210> 13
<211> 526
<212> DNA
<213> 人工序列
<220>
<223> 实施例中包括的序列
<220>
<221> misc_feature
<222> (1)..(4)
<223> n = 2'-O-甲基尿嘧啶
<400> 13
nnnntttttt tttttttttt tttttttttt tttttttttt tttttttttg ccatcagatt 60
gtgtttgtta gtcgctggtt gtttctgttg gtgctgatat tgcttttgat gccgacccta 120
aattttttgc ctgtttggtt cgctttgagt cttcttcggt tccgactacc ctcccgactg 180
cctatgatgt ttatcctttg aatggtcgcc atgatggtgg ttattatacc gtcaaggact 240
gtgtgactat tgacgtcctt ccccgtacgc cgggcaataa cgtttatgtt ggtttcatgg 300
tttggtctaa ctttaccgct actaaatgcc gcggattggt ttcgctgaat caggttatta 360
aagagattat ttgtctccag ccacttaagt gaggtgattt atgtttggtg ctattgctgg 420
cggtattgct tctgctcttg ctggtggcgc catgtctaaa ttgtttggag gcggtctttt 480
tccccctttt tccccctttt tccccctttt tccccctttt tccccc 526
<210> 14
<211> 57
<212> DNA
<213> 人工序列
<220>
<223> 实施例中包括的序列
<400> 14
agcgactaac aaacacaatc tgatggcttt tttttttttt tttttttttt ttttttt 57
<210> 15
<211> 760
<212> PRT
<213> 布氏拟甲烧球菌(Methanococcoides burtonii)
<400> 15
Met Met Ile Arg Glu Leu Asp Ile Pro Arg Asp Ile Ile Gly Phe Tyr
1 5 10 15
Glu Asp Ser Gly Ile Lys Glu Leu Tyr Pro Pro Gln Ala Glu Ala Ile
20 25 30
Glu Met Gly Leu Leu Glu Lys Lys Asn Leu Leu Ala Ala Ile Pro Thr
35 40 45
Ala Ser Gly Lys Thr Leu Leu Ala Glu Leu Ala Met Ile Lys Ala Ile
50 55 60
Arg Glu Gly Gly Lys Ala Leu Tyr Ile Val Pro Leu Arg Ala Leu Ala
65 70 75 80
Ser Glu Lys Phe Glu Arg Phe Lys Glu Leu Ala Pro Phe Gly Ile Lys
85 90 95
Val Gly Ile Ser Thr Gly Asp Leu Asp Ser Arg Ala Asp Trp Leu Gly
100 105 110
Val Asn Asp Ile Ile Val Ala Thr Ser Glu Lys Thr Asp Ser Leu Leu
115 120 125
Arg Asn Gly Thr Ser Trp Met Asp Glu Ile Thr Thr Val Val Val Asp
130 135 140
Glu Ile His Leu Leu Asp Ser Lys Asn Arg Gly Pro Thr Leu Glu Val
145 150 155 160
Thr Ile Thr Lys Leu Met Arg Leu Asn Pro Asp Val Gln Val Val Ala
165 170 175
Leu Ser Ala Thr Val Gly Asn Ala Arg Glu Met Ala Asp Trp Leu Gly
180 185 190
Ala Ala Leu Val Leu Ser Glu Trp Arg Pro Thr Asp Leu His Glu Gly
195 200 205
Val Leu Phe Gly Asp Ala Ile Asn Phe Pro Gly Ser Gln Lys Lys Ile
210 215 220
Asp Arg Leu Glu Lys Asp Asp Ala Val Asn Leu Val Leu Asp Thr Ile
225 230 235 240
Lys Ala Glu Gly Gln Cys Leu Val Phe Glu Ser Ser Arg Arg Asn Cys
245 250 255
Ala Gly Phe Ala Lys Thr Ala Ser Ser Lys Val Ala Lys Ile Leu Asp
260 265 270
Asn Asp Ile Met Ile Lys Leu Ala Gly Ile Ala Glu Glu Val Glu Ser
275 280 285
Thr Gly Glu Thr Asp Thr Ala Ile Val Leu Ala Asn Cys Ile Arg Lys
290 295 300
Gly Val Ala Phe His His Ala Gly Leu Asn Ser Asn His Arg Lys Leu
305 310 315 320
Val Glu Asn Gly Phe Arg Gln Asn Leu Ile Lys Val Ile Ser Ser Thr
325 330 335
Pro Thr Leu Ala Ala Gly Leu Asn Leu Pro Ala Arg Arg Val Ile Ile
340 345 350
Arg Ser Tyr Arg Arg Phe Asp Ser Asn Phe Gly Met Gln Pro Ile Pro
355 360 365
Val Leu Glu Tyr Lys Gln Met Ala Gly Arg Ala Gly Arg Pro His Leu
370 375 380
Asp Pro Tyr Gly Glu Ser Val Leu Leu Ala Lys Thr Tyr Asp Glu Phe
385 390 395 400
Ala Gln Leu Met Glu Asn Tyr Val Glu Ala Asp Ala Glu Asp Ile Trp
405 410 415
Ser Lys Leu Gly Thr Glu Asn Ala Leu Arg Thr His Val Leu Ser Thr
420 425 430
Ile Val Asn Gly Phe Ala Ser Thr Arg Gln Glu Leu Phe Asp Phe Phe
435 440 445
Gly Ala Thr Phe Phe Ala Tyr Gln Gln Asp Lys Trp Met Leu Glu Glu
450 455 460
Val Ile Asn Asp Cys Leu Glu Phe Leu Ile Asp Lys Ala Met Val Ser
465 470 475 480
Glu Thr Glu Asp Ile Glu Asp Ala Ser Lys Leu Phe Leu Arg Gly Thr
485 490 495
Arg Leu Gly Ser Leu Val Ser Met Leu Tyr Ile Asp Pro Leu Ser Gly
500 505 510
Ser Lys Ile Val Asp Gly Phe Lys Asp Ile Gly Lys Ser Thr Gly Gly
515 520 525
Asn Met Gly Ser Leu Glu Asp Asp Lys Gly Asp Asp Ile Thr Val Thr
530 535 540
Asp Met Thr Leu Leu His Leu Val Cys Ser Thr Pro Asp Met Arg Gln
545 550 555 560
Leu Tyr Leu Arg Asn Thr Asp Tyr Thr Ile Val Asn Glu Tyr Ile Val
565 570 575
Ala His Ser Asp Glu Phe His Glu Ile Pro Asp Lys Leu Lys Glu Thr
580 585 590
Asp Tyr Glu Trp Phe Met Gly Glu Val Lys Thr Ala Met Leu Leu Glu
595 600 605
Glu Trp Val Thr Glu Val Ser Ala Glu Asp Ile Thr Arg His Phe Asn
610 615 620
Val Gly Glu Gly Asp Ile His Ala Leu Ala Asp Thr Ser Glu Trp Leu
625 630 635 640
Met His Ala Ala Ala Lys Leu Ala Glu Leu Leu Gly Val Glu Tyr Ser
645 650 655
Ser His Ala Tyr Ser Leu Glu Lys Arg Ile Arg Tyr Gly Ser Gly Leu
660 665 670
Asp Leu Met Glu Leu Val Gly Ile Arg Gly Val Gly Arg Val Arg Ala
675 680 685
Arg Lys Leu Tyr Asn Ala Gly Phe Val Ser Val Ala Lys Leu Lys Gly
690 695 700
Ala Asp Ile Ser Val Leu Ser Lys Leu Val Gly Pro Lys Val Ala Tyr
705 710 715 720
Asn Ile Leu Ser Gly Ile Gly Val Arg Val Asn Asp Lys His Phe Asn
725 730 735
Ser Ala Pro Ile Ser Ser Asn Thr Leu Asp Thr Leu Leu Asp Lys Asn
740 745 750
Gln Lys Thr Phe Asn Asp Phe Gln
755 760
<210> 16
<211> 300
<212> PRT
<213> 赤子爱胜蚓
<400> 16
Met Ser Ser Ser Thr Val Met Ala Asp Gly Phe Glu Glu Ile Glu Val
1 5 10 15
Asp Val Val Ser Val Trp Lys Glu Gly Tyr Ala Tyr Glu Asn Arg Gly
20 25 30
Asn Ser Ser Val Gln Gln Lys Ile Thr Met Thr Lys Gly Met Lys Asn
35 40 45
Leu Asn Ser Glu Thr Lys Thr Leu Thr Ala Thr His Thr Leu Gly Arg
50 55 60
Thr Leu Lys Val Gly Asp Pro Phe Glu Ile Ala Ser Val Glu Val Ser
65 70 75 80
Tyr Thr Phe Ser His Gln Lys Ser Gln Val Ser Met Thr Gln Thr Glu
85 90 95
Val Tyr Ser Ser Gln Val Ile Glu His Thr Val Thr Ile Pro Pro Asn
100 105 110
Lys Lys Phe Thr Arg Trp Lys Leu Asn Ala Asp Val Gly Gly Thr Gly
115 120 125
Ile Glu Tyr Met Tyr Leu Ile Asp Glu Val Thr Ala Ile Gly Ala Asp
130 135 140
Leu Thr Ile Pro Glu Val Asn Lys Ser Arg Ala Lys Ile Leu Val Gly
145 150 155 160
Arg Gln Ile His Leu Gly Glu Thr Glu Ile Arg Ile Lys His Ala Glu
165 170 175
Arg Lys Glu Tyr Met Thr Val Ile Ser Arg Lys Ser Trp Pro Ala Ala
180 185 190
Thr Leu Gly Asn Ser Asn Leu Phe Lys Phe Val Leu Phe Glu Asp Ser
195 200 205
Ser Gly Ile Arg Ile Lys Thr Leu Asn Thr Met Tyr Pro Gly Tyr Glu
210 215 220
Trp Ala Tyr Ser Ser Asp Gln Gly Gly Ile Tyr Phe Asp Glu Ser Ser
225 230 235 240
Asp Asn Pro Lys Gln Arg Trp Ala Leu Ser Lys Ala Met Pro Leu Arg
245 250 255
His Gly Asp Val Val Thr Phe Arg Asn Asn Phe Phe Thr Asn Ser Gly
260 265 270
Met Cys Tyr Asp Asp Gly Pro Ala Thr Asn Val Tyr Cys Leu Glu Lys
275 280 285
Arg Glu Asp Lys Trp Ile Leu Glu Val Val Asn Thr
290 295 300
<210> 17
<211> 300
<212> PRT
<213> 赤子爱胜蚓
<400> 17
Met Ser Ser Arg Ala Gly Ile Ala Glu Gly Tyr Glu Gln Ile Glu Val
1 5 10 15
Asp Val Val Ala Val Trp Lys Glu Gly Tyr Val Tyr Glu Asn Arg Gly
20 25 30
Ser Thr Ser Val Glu Gln Lys Ile Lys Ile Thr Lys Gly Met Arg Asn
35 40 45
Leu Asn Ser Glu Thr Lys Thr Leu Thr Ala Ser His Ser Ile Gly Ser
50 55 60
Thr Ile Ser Thr Gly Asp Leu Phe Glu Ile Ala Thr Val Asp Val Ser
65 70 75 80
Tyr Ser Tyr Ser His Glu Glu Ser Gln Val Ser Met Thr Glu Thr Glu
85 90 95
Val Tyr Glu Ser Lys Glu Ile Glu His Thr Ile Thr Ile Pro Pro Thr
100 105 110
Ser Lys Phe Thr Arg Trp Gln Leu Asn Ala Asp Val Gly Gly Ala Asp
115 120 125
Ile Glu Tyr Met Tyr Leu Ile Asp Glu Val Thr Pro Ile Gly Gly Thr
130 135 140
Leu Ser Ile Pro Gln Val Ile Lys Ser Arg Ala Lys Ile Leu Val Gly
145 150 155 160
Arg Glu Ile Tyr Leu Gly Glu Thr Glu Ile Arg Ile Lys His Ala Asp
165 170 175
Arg Lys Glu Tyr Met Thr Val Val Ser Arg Lys Ser Trp Pro Ala Ala
180 185 190
Thr Leu Gly His Ser Lys Leu Tyr Lys Phe Val Leu Tyr Glu Asp Met
195 200 205
Tyr Gly Phe Arg Ile Lys Thr Leu Asn Thr Met Tyr Ser Gly Tyr Glu
210 215 220
Tyr Ala Tyr Ser Ser Asp Gln Gly Gly Ile Tyr Phe Asp Gln Gly Ser
225 230 235 240
Asp Asn Pro Lys Gln Arg Trp Ala Ile Asn Lys Ser Leu Pro Leu Arg
245 250 255
His Gly Asp Val Val Thr Phe Met Asn Lys Tyr Phe Thr Arg Ser Gly
260 265 270
Leu Cys Tyr Tyr Asp Gly Pro Ala Thr Asp Val Tyr Cys Leu Asp Lys
275 280 285
Arg Glu Asp Lys Trp Ile Leu Glu Val Val Lys Pro
290 295 300
<210> 18
<211> 300
<212> PRT
<213> 赤子爱胜蚓
<400> 18
Met Ser Ala Thr Ala Val Thr Ala Asp Gly Leu Glu Glu Ile Glu Val
1 5 10 15
Asp Val Val Ala Val Trp Lys Glu Gly Tyr Val Tyr Glu Asn Arg Gly
20 25 30
Asp Thr Ser Val Glu Gln Lys Ile Thr Met Thr Lys Gly Met Lys Asn
35 40 45
Leu Asn Ser Glu Thr Lys Thr Leu Thr Ala Thr His Thr Val Gly Arg
50 55 60
Thr Leu Lys Val Gly Asp Pro Phe Glu Ile Gly Ser Val Glu Val Ser
65 70 75 80
Tyr Ser Phe Ser His Gln Glu Ser Gln Val Ser Met Thr Gln Thr Glu
85 90 95
Val Tyr Ser Ser Gln Val Ile Glu His Thr Val Thr Ile Pro Pro Thr
100 105 110
Ser Lys Phe Thr Arg Trp Lys Leu Asn Ala Asp Val Gly Gly Thr Asp
115 120 125
Ile Glu Tyr Met Tyr Leu Ile Asp Glu Val Thr Pro Ile Ser Val Thr
130 135 140
Gln Thr Ile Pro Gln Val Ile Arg Ser Arg Ala Lys Ile Leu Val Gly
145 150 155 160
Arg Gln Ile His Leu Gly Thr Thr Ala Val Arg Ile Lys His Ala Glu
165 170 175
Arg Gln Glu Tyr Met Thr Val Ile Glu Arg Lys Lys Trp Pro Ala Ala
180 185 190
Thr Leu Gly Lys Ser Asn Leu Phe Lys Phe Val Leu Phe Glu Asp Ser
195 200 205
Ser Gly Thr Arg Ile Lys Thr Leu Asn Thr Met Tyr Pro Gly Tyr Glu
210 215 220
Trp Ala Tyr Ser Ser Asp Gln Gly Gly Val Tyr Phe Asp Glu Ser Ser
225 230 235 240
Asp Asn Pro Lys Gln Arg Trp Ala Leu Ser Lys Ala Leu Pro Leu Arg
245 250 255
His Gly Asp Val Val Thr Phe Met Asn Lys Tyr Phe Thr Asn Ser Gly
260 265 270
Leu Cys Tyr Asp Asp Gly Pro Ala Thr Asn Val Tyr Cys Leu Asp Lys
275 280 285
Arg Glu Asp Lys Trp Ile Leu Glu Val Val Asn Pro
290 295 300
<210> 19
<211> 252
<212> PRT
<213> 苏云金芽孢杆菌(Bacillus thuringiensis)
<400> 19
Met Asp Val Ile Arg Glu Tyr Leu Met Phe Asn Glu Leu Ser Ala Leu
1 5 10 15
Ser Ser Ser Pro Glu Ser Val Arg Ser Arg Phe Ser Ser Ile Tyr Gly
20 25 30
Thr Asn Pro Asp Gly Ile Ala Leu Asn Asn Glu Thr Tyr Phe Asn Ala
35 40 45
Val Lys Pro Pro Ile Thr Ala Gln Tyr Gly Tyr Tyr Cys Tyr Lys Asn
50 55 60
Val Gly Thr Val Gln Tyr Val Asn Arg Pro Thr Asp Ile Asn Pro Asn
65 70 75 80
Val Ile Leu Ala Gln Asp Thr Leu Thr Asn Asn Thr Asn Glu Pro Phe
85 90 95
Thr Thr Thr Ile Thr Ile Thr Gly Ser Phe Thr Asn Thr Ser Thr Val
100 105 110
Thr Ser Ser Thr Thr Thr Gly Phe Lys Phe Thr Ser Lys Leu Ser Ile
115 120 125
Lys Lys Val Phe Glu Ile Gly Gly Glu Val Ser Phe Ser Thr Thr Ile
130 135 140
Gly Thr Ser Glu Thr Thr Thr Glu Thr Ile Thr Val Ser Lys Ser Val
145 150 155 160
Thr Val Thr Val Pro Ala Gln Ser Arg Arg Thr Ile Gln Leu Thr Ala
165 170 175
Lys Ile Ala Lys Glu Ser Ala Asp Phe Ser Ala Pro Ile Thr Val Asp
180 185 190
Gly Tyr Phe Gly Ala Asn Phe Pro Lys Arg Val Gly Pro Gly Gly His
195 200 205
Tyr Phe Trp Phe Asn Pro Ala Arg Asp Val Leu Asn Thr Thr Ser Gly
210 215 220
Thr Leu Arg Gly Thr Val Thr Asn Val Ser Ser Phe Asp Phe Gln Thr
225 230 235 240
Ile Val Gln Pro Ala Arg Ser Leu Leu Asp Glu Gln
245 250
Claims (12)
1.一种突变体胞溶素单体，其为SEQ ID NO:2的变体，其中，E84用N或Q取代且E92用N或Q取代，和所述变体具有以下取代中的一个或多个：N46S、N48S、E50S、R52S、D68S、E71S、E76S、E85K、E94N/S、E97N/S、E102S、D121S/N、D126G/N、E128N/S、E135S和E167A；其中，所述突变体胞溶素单体能够形成孔。
2.根据权利要求1所述的突变体胞溶素单体，其中所述变体含有以下取代中的一个或多个：E85K、E97N/S和D126G。
3.根据权利要求1所述的突变体胞溶素单体，其中所述变体含有以下取代：
i.E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个；
ii.E76S,E84Q,E85K,E92Q,E97S,D126G和E167A中的一个或多个；
iii.E84Q,E85K,E92Q,E97S,D126G,E167A和E71S中的一个或多个；
iv.E84Q,E85K,E92Q,E97S,D126G,E167A和E94S中的一个或多个；
v.E84Q,E85K,E92Q,E97S,D126G,E167A和E128S中的一个或多个；
vi.E84Q,E85K,E92Q,E97S,D126G,E167A和E135S中的一个或多个；
vii.E84Q,E85K,E92Q,E97S,D126G和E135S中的一个或多个；
viii.E84Q,E85K,M90S,E92Q,E97S和D126G中的一个或多个；
ix.E84Q,E85S,E92Q,E97S和D126G中的一个或多个；
x.E84S,E85K,E92Q,E97S和D126G中的一个或多个；
xi.R52S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个；
xii.N46S,E84Q,E85K,E92Q,E97S和D126G中的一个或多个；
xiii.E84Q,E85K,E92Q和E97S中的一个或多个；
xiv.E84Q,E85K,E92Q,E97S和D126G中的一个或多个；
xv.E84Q,E85K,E92Q,E97S和E167A中的一个或多个；
xvi.E84Q,E85K,E92Q,D126G和E167A中的一个或多个；或
xvii.E84Q,E92Q,E97S,D126G和E167A中的一个或多个。
4.根据权利要求3所述的突变体胞溶素单体，其中所述变体包含i至xvii的任一个中的所有取代。
5.一种构造，含有两个或更多个共价连接的源自胞溶素的单体，其中所述单体中的至少一个为如权利要求1至4中任一项中限定的突变体胞溶素单体。
6.根据权利要求5所述的构造，其中(i)所述两个或更多个单体是相同的或不同的；和/或(ii)至少一个单体包含SEQ ID NO:2中所示的序列；和/或(iii)所述构造包含两个单体；和/或(iv)所述单体是基因融合的；和/或(v)所述单体通过连接体而连接。
7.一种多核苷酸，其编码根据权利要求1至4中任一项所述的突变体胞溶素单体或根据权利要求5所述的构造。
8.一种源自胞溶素的同源寡聚孔，包含足够数目的根据权利要求1至4中任一项所述的突变体胞溶素单体。
9.一种源自胞溶素的异源寡聚孔，包含至少一个根据权利要求1至4中任一项所述的突变体胞溶素单体。
10.一种表征目标分析物的方法，包括：
(a)使所述目标分析物与根据权利要求8或9所述的孔接触，使得所述目标分析物移动穿过所述孔；和
(b)在所述分析物相对于所述孔移动时获取一个或多个测量值，其中所述测量值表示所述目标分析物的一个或多个特征并由此表征所述目标分析物。
11.根据权利要求8或9所述的孔在表征目标分析物中的应用。
12.一种试剂盒，用于表征目标多核苷酸，所述试剂盒包含(a)根据权利要求8或9所述的孔，和(b)多核苷酸结合蛋白。
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261622174P | 2012-04-10 | 2012-04-10 | |
| US61/622,174 | 2012-04-10 | ||
| CN201380030527.2A CN104350067A (zh) | 2012-04-10 | 2013-03-15 | 突变胞溶素孔 |
| PCT/GB2013/050667 WO2013153359A1 (en) | 2012-04-10 | 2013-03-15 | Mutant lysenin pores |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380030527.2A Division CN104350067A (zh) | 2012-04-10 | 2013-03-15 | 突变胞溶素孔 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112646019A CN112646019A (zh) | 2021-04-13 |
| CN112646019B true CN112646019B (zh) | 2022-08-16 |
Family
ID=47915292
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380030527.2A Pending CN104350067A (zh) | 2012-04-10 | 2013-03-15 | 突变胞溶素孔 |
| CN202011579254.5A Active CN112646019B (zh) | 2012-04-10 | 2013-03-15 | 突变胞溶素孔 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380030527.2A Pending CN104350067A (zh) | 2012-04-10 | 2013-03-15 | 突变胞溶素孔 |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US9777049B2 (zh) |
| EP (2) | EP2836506B1 (zh) |
| JP (2) | JP6271505B2 (zh) |
| KR (1) | KR102083695B1 (zh) |
| CN (2) | CN104350067A (zh) |
| AU (1) | AU2013246702B2 (zh) |
| BR (1) | BR112014025157B1 (zh) |
| CA (1) | CA2869546C (zh) |
| WO (1) | WO2013153359A1 (zh) |
Families Citing this family (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2122344B8 (en) | 2007-02-20 | 2019-08-21 | Oxford Nanopore Technologies Limited | Lipid bilayer sensor system |
| GB0724736D0 (en) | 2007-12-19 | 2008-01-30 | Oxford Nanolabs Ltd | Formation of layers of amphiphilic molecules |
| GB0820927D0 (en) | 2008-11-14 | 2008-12-24 | Isis Innovation | Method |
| AU2010209528B2 (en) | 2009-01-30 | 2015-10-01 | Oxford Nanopore Technologies Limited | Adaptors for nucleic acid constructs in transmembrane sequencing |
| GB0905140D0 (en) | 2009-03-25 | 2009-05-06 | Isis Innovation | Method |
| WO2012107778A2 (en) | 2011-02-11 | 2012-08-16 | Oxford Nanopore Technologies Limited | Mutant pores |
| WO2012164270A1 (en) | 2011-05-27 | 2012-12-06 | Oxford Nanopore Technologies Limited | Coupling method |
| AU2012288629B2 (en) | 2011-07-25 | 2017-02-02 | Oxford Nanopore Technologies Limited | Hairpin loop method for double strand polynucleotide sequencing using transmembrane pores |
| US9758823B2 (en) | 2011-10-21 | 2017-09-12 | Oxford Nanopore Technologies Limited | Enzyme method |
| US10385382B2 (en) | 2011-12-29 | 2019-08-20 | Oxford Nanopore Technologies Ltd. | Enzyme method |
| GB201202519D0 (en) | 2012-02-13 | 2012-03-28 | Oxford Nanopore Tech Ltd | Apparatus for supporting an array of layers of amphiphilic molecules and method of forming an array of layers of amphiphilic molecules |
| AU2013220156B2 (en) | 2012-02-15 | 2018-08-09 | Oxford Nanopore Technologies Limited | Aptamer method |
| EP3736339B1 (en) | 2012-02-16 | 2022-07-27 | Oxford Nanopore Technologies plc | Analysis of measurements of a polymer |
| EP2836506B1 (en) | 2012-04-10 | 2017-04-19 | Oxford Nanopore Technologies Limited | Mutant lysenin pores |
| US11155860B2 (en) | 2012-07-19 | 2021-10-26 | Oxford Nanopore Technologies Ltd. | SSB method |
| CA2879355C (en) | 2012-07-19 | 2021-09-21 | Oxford Nanopore Technologies Limited | Helicase construct and its use in characterising polynucleotides |
| CA2879261C (en) | 2012-07-19 | 2022-12-06 | Oxford Nanopore Technologies Limited | Modified helicases |
| US9551023B2 (en) | 2012-09-14 | 2017-01-24 | Oxford Nanopore Technologies Ltd. | Sample preparation method |
| GB201313121D0 (en) | 2013-07-23 | 2013-09-04 | Oxford Nanopore Tech Ltd | Array of volumes of polar medium |
| US9995728B2 (en) | 2012-11-06 | 2018-06-12 | Oxford Nanopore Technologies Ltd. | Quadruplex method |
| GB201222928D0 (en) | 2012-12-19 | 2013-01-30 | Oxford Nanopore Tech Ltd | Analysis of a polynucleotide |
| AU2014224432B2 (en) | 2013-03-08 | 2019-10-24 | Oxford Nanopore Technologies Limited | Enzyme stalling method |
| GB201314695D0 (en) | 2013-08-16 | 2013-10-02 | Oxford Nanopore Tech Ltd | Method |
| GB201318465D0 (en) | 2013-10-18 | 2013-12-04 | Oxford Nanopore Tech Ltd | Method |
| GB201313477D0 (en) | 2013-07-29 | 2013-09-11 | Univ Leuven Kath | Nanopore biosensors for detection of proteins and nucleic acids |
| CN105899678A (zh) | 2013-10-18 | 2016-08-24 | 牛津纳米孔技术公司 | 经修饰的酶 |
| GB201406151D0 (en) | 2014-04-04 | 2014-05-21 | Oxford Nanopore Tech Ltd | Method |
| CN105934522B (zh) | 2013-11-26 | 2021-07-20 | 伊鲁米那股份有限公司 | 用于多核苷酸测序的组合物和方法 |
| AU2015208919B9 (en) | 2014-01-22 | 2021-04-01 | Oxford Nanopore Technologies Limited | Method for attaching one or more polynucleotide binding proteins to a target polynucleotide |
| GB201406155D0 (en) | 2014-04-04 | 2014-05-21 | Oxford Nanopore Tech Ltd | Method |
| US10359395B2 (en) | 2014-02-19 | 2019-07-23 | University Of Washington | Nanopore-based analysis of protein characteristics |
| GB201403096D0 (en) | 2014-02-21 | 2014-04-09 | Oxford Nanopore Tech Ltd | Sample preparation method |
| US10337060B2 (en) | 2014-04-04 | 2019-07-02 | Oxford Nanopore Technologies Ltd. | Method for characterising a double stranded nucleic acid using a nano-pore and anchor molecules at both ends of said nucleic acid |
| EP3137490B1 (en) | 2014-05-02 | 2021-01-27 | Oxford Nanopore Technologies Limited | Mutant pores |
| GB201417712D0 (en) | 2014-10-07 | 2014-11-19 | Oxford Nanopore Tech Ltd | Method |
| ES2846746T3 (es) | 2014-06-03 | 2021-07-29 | Illumina Inc | Composiciones, sistemas y métodos para detectar acontecimientos usando fijaciones ancladas o adyacentes a nanoporos |
| EP3172342A4 (en) | 2014-07-25 | 2017-12-13 | GE Healthcare UK Limited | Screening and monitoring the progression of type 2 diabetes by the molecular identification of gut flora using fta as a faecal collection device |
| KR20170042794A (ko) | 2014-09-01 | 2017-04-19 | 브이아이비 브이지더블유 | 돌연변이체 csgg 포어 |
| US10266885B2 (en) | 2014-10-07 | 2019-04-23 | Oxford Nanopore Technologies Ltd. | Mutant pores |
| GB201418159D0 (en) | 2014-10-14 | 2014-11-26 | Oxford Nanopore Tech Ltd | Method |
| KR102551897B1 (ko) | 2014-10-16 | 2023-07-06 | 옥스포드 나노포어 테크놀로지즈 피엘씨 | 폴리머의 분석 |
| GB201418469D0 (en) | 2014-10-17 | 2014-12-03 | Oxford Nanopore Tech Ltd | Method |
| JP6824881B2 (ja) | 2014-10-17 | 2021-02-03 | オックスフォード ナノポール テクノロジーズ リミテッド | ナノ細孔ｒｎａを特徴付けるための方法 |
| JP6800862B2 (ja) | 2015-02-05 | 2020-12-16 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 流体通路を含むナノポアセンサ |
| GB201502810D0 (en) | 2015-02-19 | 2015-04-08 | Oxford Nanopore Tech Ltd | Method |
| GB201502809D0 (en) | 2015-02-19 | 2015-04-08 | Oxford Nanopore Tech Ltd | Mutant pore |
| US11169138B2 (en) | 2015-04-14 | 2021-11-09 | Katholieke Universiteit Leuven | Nanopores with internal protein adaptors |
| GB201508003D0 (en) | 2015-05-11 | 2015-06-24 | Oxford Nanopore Tech Ltd | Apparatus and methods for measuring an electrical current |
| GB201508669D0 (en) | 2015-05-20 | 2015-07-01 | Oxford Nanopore Tech Ltd | Methods and apparatus for forming apertures in a solid state membrane using dielectric breakdown |
| JP6595005B2 (ja) | 2015-06-03 | 2019-10-23 | イラミーナ インコーポレーテッド | ナノポアに隣接するポリメラーゼに固定されたテザーを用いるポリヌクレオチドの配列決定のための組成物、システム、および方法 |
| EP3387432B1 (en) | 2015-12-08 | 2022-09-28 | Katholieke Universiteit Leuven KU Leuven Research & Development | Modified nanopores, compositions comprising the same, and uses thereof |
| JP6579948B2 (ja) | 2015-12-24 | 2019-09-25 | 株式会社日立ハイテクノロジーズ | 生体ポリマを分析するための測定試薬及び分析デバイス |
| KR102222188B1 (ko) * | 2016-03-02 | 2021-03-02 | 옥스포드 나노포어 테크놀로지즈 리미티드 | 돌연변이체 기공 |
| EP4122949B1 (en) | 2016-04-06 | 2024-06-05 | Oxford Nanopore Technologies plc | Mutant pore |
| CN109196116B (zh) | 2016-05-25 | 2022-09-27 | 牛津纳米孔科技公开有限公司 | 一种表征靶多核苷酸的方法 |
| GB201609221D0 (en) | 2016-05-25 | 2016-07-06 | Oxford Nanopore Tech Ltd | Method |
| GB201609220D0 (en) | 2016-05-25 | 2016-07-06 | Oxford Nanopore Tech Ltd | Method |
| GB201611770D0 (en) | 2016-07-06 | 2016-08-17 | Oxford Nanopore Tech | Microfluidic device |
| GB201616590D0 (en) | 2016-09-29 | 2016-11-16 | Oxford Nanopore Technologies Limited | Method |
| GB201617886D0 (en) | 2016-10-21 | 2016-12-07 | Oxford Nanopore Technologies Limited | Method |
| GB201620450D0 (en) | 2016-12-01 | 2017-01-18 | Oxford Nanopore Tech Ltd | Method |
| EP3580228B1 (en) | 2017-02-10 | 2021-07-28 | Oxford Nanopore Technologies Limited | Modified nanopores, compositions comprising the same, and uses thereof |
| US10913978B2 (en) | 2017-02-14 | 2021-02-09 | Axbio Inc. | Apparatus and methods for continuous diagnostics of macromolecules |
| GB201707122D0 (en) | 2017-05-04 | 2017-06-21 | Oxford Nanopore Tech Ltd | Pore |
| GB201707138D0 (en) | 2017-05-04 | 2017-06-21 | Oxford Nanopore Tech Ltd | Machine learning analysis of nanopore measurements |
| GB201707140D0 (en) | 2017-05-04 | 2017-06-21 | Oxford Nanopore Tech Ltd | Method |
| EP3645552B1 (en) | 2017-06-30 | 2023-06-28 | Vib Vzw | Novel protein pores |
| GB2569630B (en) | 2017-12-21 | 2022-10-12 | Sharp Life Science Eu Ltd | Droplet Interfaces in Electro-wetting Devices |
| GB201807793D0 (en) | 2018-05-14 | 2018-06-27 | Oxford Nanopore Tech Ltd | Method |
| WO2019227013A1 (en) | 2018-05-24 | 2019-11-28 | Oxford Nanopore Technologies Inc. | Droplet interfaces in electro-wetting devices |
| GB201808556D0 (en) | 2018-05-24 | 2018-07-11 | Oxford Nanopore Tech Ltd | Method |
| GB201809323D0 (en) | 2018-06-06 | 2018-07-25 | Oxford Nanopore Tech Ltd | Method |
| GB201814369D0 (en) | 2018-09-04 | 2018-10-17 | Oxford Nanopore Tech Ltd | Method for determining a polymersequence |
| CN113195736A (zh) | 2018-11-08 | 2021-07-30 | 牛津纳米孔科技公司 | 孔 |
| GB201818216D0 (en) | 2018-11-08 | 2018-12-26 | Oxford Nanopore Tech Ltd | Pore |
| GB201819378D0 (en) | 2018-11-28 | 2019-01-09 | Oxford Nanopore Tech Ltd | Analysis of nanopore signal using a machine-learning technique |
| CN113164954B (zh) | 2018-11-28 | 2023-10-20 | 牛津纳米孔科技公开有限公司 | 感测系统和操作方法 |
| GB201821155D0 (en) | 2018-12-21 | 2019-02-06 | Oxford Nanopore Tech Ltd | Method |
| KR20210138594A (ko) | 2019-03-12 | 2021-11-19 | 옥스포드 나노포어 테크놀로지즈 피엘씨 | 나노포어 감지 디바이스 및 이를 작동하는 방법 및 형성하는 방법 |
| GB2580988B (en) | 2019-03-19 | 2022-04-13 | Oxford Nanopore Tech Ltd | Current measurement apparatus, molecular entity sensing apparatus, method of measuring a current, method of sensing a molecular entity |
| CN110093399A (zh) * | 2019-04-22 | 2019-08-06 | 武汉大学 | 一种利用二磷酸尿嘧啶脱氧核苷酸检测核酸中腺嘌呤n6位发生甲基化修饰的方法 |
| GB201907243D0 (en) | 2019-05-22 | 2019-07-03 | Oxford Nanopore Tech Ltd | Sensing interactions between molecular entities and nanapores |
| GB201907246D0 (en) | 2019-05-22 | 2019-07-03 | Oxford Nanopore Tech Ltd | Method |
| GB201907244D0 (en) | 2019-05-22 | 2019-07-03 | Oxford Nanopore Tech Ltd | Method |
| GB201915480D0 (en) | 2019-10-25 | 2019-12-11 | Oxford Nanopore Tech Ltd | Improved nanopore sensing device, components and method of manufacture |
| GB201917060D0 (en) | 2019-11-22 | 2020-01-08 | Oxford Nanopore Tech Ltd | Method |
| EP4070092B1 (en) | 2019-12-02 | 2023-08-30 | Oxford Nanopore Technologies PLC | Method of characterising a target polypeptide using a nanopore |
| GB201917742D0 (en) | 2019-12-04 | 2020-01-15 | Oxford Nanopore Tech Ltd | Method |
| GB202004944D0 (en) | 2020-04-03 | 2020-05-20 | King S College London | Method |
| GB202016874D0 (en) | 2020-10-23 | 2020-12-09 | Oxford Nanopore Tech Ltd | Nanopore support structure and manufacture thereof |
| WO2021255475A1 (en) | 2020-06-18 | 2021-12-23 | Oxford Nanopore Technologies Limited | A method of selectively characterising a polynucleotide using a detector |
| GB202009349D0 (en) | 2020-06-18 | 2020-08-05 | Oxford Nanopore Tech Ltd | Method |
| AU2021291140A1 (en) | 2020-06-18 | 2023-02-02 | Oxford Nanopore Technologies Limited | Method of characterising a polynucleotide moving through a nanopore |
| US20230349882A1 (en) | 2020-07-17 | 2023-11-02 | Oxford Nanopore Technologies Plc | Nanopore sensing device |
| WO2022020461A1 (en) | 2020-07-22 | 2022-01-27 | Oxford Nanopore Technologies Inc. | Solid state nanopore formation |
| EP4222742A1 (en) | 2020-09-29 | 2023-08-09 | Ecole Polytechnique Federale De Lausanne (Epfl) | Systems and methods for digital information decoding and data storage in hybrid macromolecules |
| GB202015993D0 (en) | 2020-10-08 | 2020-11-25 | Oxford Nanopore Tech Ltd | Method |
| EP4314810A1 (en) | 2021-03-31 | 2024-02-07 | Illumina, Inc. | Nanopore sensor devices |
| GB202107192D0 (en) | 2021-05-19 | 2021-06-30 | Oxford Nanopore Tech Ltd | Method |
| CN117337333A (zh) | 2021-05-19 | 2024-01-02 | 牛津纳米孔科技公开有限公司 | 用于补体链测序的方法 |
| GB202107354D0 (en) | 2021-05-24 | 2021-07-07 | Oxford Nanopore Tech Ltd | Method |
| GB2610380A (en) | 2021-08-23 | 2023-03-08 | Cambridge Entpr Ltd | Nucleic acid detection |
| GB202112235D0 (en) | 2021-08-26 | 2021-10-13 | Oxford Nanopore Tech Ltd | Nanopore |
| CA3223744A1 (en) | 2021-09-22 | 2023-03-30 | Jeffrey Mandell | Sequencing polynucleotides using nanopores |
| GB202113935D0 (en) | 2021-09-29 | 2021-11-10 | Cambridge Entpr Ltd | Nucleic acid characterisation |
| WO2023081031A1 (en) | 2021-11-08 | 2023-05-11 | Illumina, Inc. | Identifying nucleotides using changes in impedance between electrodes |
| WO2023094806A1 (en) | 2021-11-29 | 2023-06-01 | Oxford Nanopore Technologies Plc | Nanopore measurement signal analysis |
| GB202118908D0 (en) | 2021-12-23 | 2022-02-09 | Oxford Nanopore Tech Ltd | Method |
| GB202118906D0 (en) | 2021-12-23 | 2022-02-09 | Oxford Nanopore Tech Ltd | Method |
| US20240076322A1 (en) | 2022-03-31 | 2024-03-07 | Illumina Cambridge Limited | Barriers including cross-linked amphiphilic molecules, and methods of making the same |
| US20230312856A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Cambridge Limited | Nanopore devices including barriers using diblock or triblock copolymers, and methods of making the same |
| WO2023187001A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Cambridge Limited | Devices including osmotically balanced barriers, and methods of making and using the same |
| WO2023187081A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Cambridge Limited | Methods for inserting nanopores into polymeric membranes using chaotropic solvents |
| US20230381718A1 (en) | 2022-03-31 | 2023-11-30 | Illumina Cambridge Limited | Barriers including molecules covalently bonded to amphiphilic molecules, and methods of making the same |
| WO2023187110A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Cambridge Limited | Amphiphilic polymers to be used in barriers and preparation thereof, barriers with nanopores and preparation thereof |
| WO2023187111A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Cambridge Limited | Barriers including biological nanopore for dna sequencing, the barriers being made of co-polymers with end and/or middle groups, and methods of making the same |
| WO2023222657A1 (en) | 2022-05-17 | 2023-11-23 | Oxford Nanopore Technologies Plc | Method and adaptors |
| GB202207267D0 (en) | 2022-05-18 | 2022-06-29 | Oxford Nanopore Tech Plc | Calibration and profiling of a nanopore array device |
| WO2023229884A2 (en) | 2022-05-27 | 2023-11-30 | Illumina, Inc. | 3'-blocked nucleotides, methods of deblocking the same, and methods of synthesizing polynucleotides using the same |
| GB202215442D0 (en) | 2022-10-19 | 2022-11-30 | Oxford Nanopore Tech Plc | Analysis of a polymer |
| GB202216162D0 (en) | 2022-10-31 | 2022-12-14 | Oxford Nanopore Tech Plc | Method |
| EP4362028A1 (en) | 2022-10-31 | 2024-05-01 | Ecole Polytechnique Federale De Lausanne (Epfl) | Mutant aerolysin and uses thereof |
| WO2024094966A1 (en) | 2022-11-01 | 2024-05-10 | Oxford Nanopore Technologies Plc | Biochemical analysis system and method of controlling a biochemical analysis system |
| GB202216905D0 (en) | 2022-11-11 | 2022-12-28 | Oxford Nanopore Tech Plc | Novel pore monomers and pores |
| GB202307486D0 (en) | 2023-05-18 | 2023-07-05 | Oxford Nanopore Tech Plc | Method |
| GB202401864D0 (en) | 2024-02-12 | 2024-03-27 | Fund Centre De Regulacio Genòmica | A method of detecting non-canonical bases in sequencing data |
Family Cites Families (151)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI82266C (fi) | 1982-10-19 | 1991-02-11 | Cetus Corp | Foerfarande foer framstaellning av il-2 -mutein. |
| US5198543A (en) | 1989-03-24 | 1993-03-30 | Consejo Superior Investigaciones Cientificas | PHI29 DNA polymerase |
| US5777078A (en) | 1993-04-28 | 1998-07-07 | Worcester Foundation For Experimental Biology | Triggered pore-forming agents |
| CA2160909A1 (en) | 1993-04-28 | 1994-11-10 | Hagan Bayley | Cell-targeted lytic pore-forming agents |
| DE4320201A1 (de) | 1993-06-18 | 1995-01-12 | Asta Medica Ag | Verwendung von Cetrorelix und weiteren Nona- und Dekapeptiden zur Herstellung eines Arzneimittels zur Bekämpfung von Aids und zur Wachstumsstimulation |
| US5386373A (en) | 1993-08-05 | 1995-01-31 | Pavilion Technologies, Inc. | Virtual continuous emission monitoring system with sensor validation |
| US5561043A (en) | 1994-01-31 | 1996-10-01 | Trustees Of Boston University | Self-assembling multimeric nucleic acid constructs |
| US7569341B2 (en) | 1994-01-31 | 2009-08-04 | Trustees Of Boston University | Nucleic acid directed immobilization arrays and methods of assembly |
| US6362002B1 (en) | 1995-03-17 | 2002-03-26 | President And Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| US5795782A (en) | 1995-03-17 | 1998-08-18 | President & Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| JP3891620B2 (ja) | 1996-11-14 | 2007-03-14 | 株式会社アイシン・コスモス研究所 | ヘアピン型構造の核酸プローブ分子、及び該核酸プローブ分子を利用した核酸検出方法 |
| US20020197614A1 (en) | 1997-05-16 | 2002-12-26 | Mosaic Technologies, Inc. | Electrophoretic analysis of target molecules using adapter molecules |
| AU8586298A (en) | 1997-07-25 | 1999-02-16 | University Of Massachusetts | Designed protein pores as components for biosensors |
| US6087099A (en) | 1997-09-08 | 2000-07-11 | Myriad Genetics, Inc. | Method for sequencing both strands of a double stranded DNA in a single sequencing reaction |
| US6127166A (en) | 1997-11-03 | 2000-10-03 | Bayley; Hagan | Molluscan ligament polypeptides and genes encoding them |
| JPH11137260A (ja) | 1997-11-06 | 1999-05-25 | Soyaku Gijutsu Kenkyusho:Kk | 抗インフルエンザウイルス環状ダンベル型ｒｎａ−ｄｎａキメラ化合物及び抗インフルエンザウイルス剤 |
| US6123819A (en) | 1997-11-12 | 2000-09-26 | Protiveris, Inc. | Nanoelectrode arrays |
| DE19826758C1 (de) | 1998-06-15 | 1999-10-21 | Soft Gene Gmbh | Darstellung von linearen kovalent geschlossenen DNA-Molekülen als Expressionskonstrukte |
| US6743605B1 (en) | 1998-06-24 | 2004-06-01 | Enzo Life Sciences, Inc. | Linear amplification of specific nucleic acid sequences |
| US7155344B1 (en) | 1998-07-27 | 2006-12-26 | Caliper Life Sciences, Inc. | Distributed database for analytical instruments |
| US6150112A (en) | 1998-09-18 | 2000-11-21 | Yale University | Methods for identifying DNA sequences for use in comparison of DNA samples by their lack of polymorphism using Y shape adaptors |
| US6267872B1 (en) | 1998-11-06 | 2001-07-31 | The Regents Of The University Of California | Miniature support for thin films containing single channels or nanopores and methods for using same |
| US6426231B1 (en) | 1998-11-18 | 2002-07-30 | The Texas A&M University System | Analyte sensing mediated by adapter/carrier molecules |
| NO986133D0 (no) | 1998-12-23 | 1998-12-23 | Preben Lexow | FremgangsmÕte for DNA-sekvensering |
| US6627067B1 (en) | 1999-06-22 | 2003-09-30 | President And Fellows Of Harvard College | Molecular and atomic scale evaluation of biopolymers |
| AU5668100A (en) | 1999-06-29 | 2001-01-22 | University Health Network | Peptide conjugates for the stabilization of membrane proteins and interactions with biological membranes |
| AU7901300A (en) | 1999-08-31 | 2001-03-26 | Stefan Bossmann | Method for producing a channel-forming protein |
| EP1238105A2 (en) | 1999-12-02 | 2002-09-11 | Molecular Staging Inc. | Generation of single-strand circular dna from linear self-annealing segments |
| EP1255772A2 (en) | 2000-02-11 | 2002-11-13 | The Texas A & M University System | Biosensor compositions and methods of use |
| WO2001062943A1 (en) | 2000-02-25 | 2001-08-30 | Invitrogen Corporation | Topoisomerase linker-mediated amplification methods |
| AU5091201A (en) | 2000-03-21 | 2001-10-03 | Curagen Corp | Vegf-modulated genes and methods employing them |
| ATE382055T1 (de) | 2000-03-22 | 2008-01-15 | Curagen Corp | Wnt-1 verwandte polypeptide und dafür kodierende nukleinsäuren |
| US7001792B2 (en) | 2000-04-24 | 2006-02-21 | Eagle Research & Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
| DE10146902A1 (de) | 2000-09-25 | 2002-09-19 | Sensovation Ag | Bildsensor, Vorrichtung und Verfahren für optische Messungen |
| AU2002239284A1 (en) | 2000-11-27 | 2002-06-03 | The Regents Of The University Of California | Methods and devices for characterizing duplex nucleic acid molecules |
| US20030087232A1 (en) | 2001-01-25 | 2003-05-08 | Fred Christians | Methods for screening polypeptides |
| US7807408B2 (en) | 2001-03-19 | 2010-10-05 | President & Fellows Of Harvard College | Directed evolution of proteins |
| JP2002355035A (ja) * | 2001-05-08 | 2002-12-10 | Inst Of Physical & Chemical Res | スフィンゴミエリン検出プローブ |
| US6995236B2 (en) * | 2001-05-08 | 2006-02-07 | Riken | Sphingomyelin detecting probe |
| US6863833B1 (en) | 2001-06-29 | 2005-03-08 | The Board Of Trustees Of The Leland Stanford Junior University | Microfabricated apertures for supporting bilayer lipid membranes |
| EP1585954B1 (en) | 2001-07-03 | 2014-03-26 | The Regents of The University of California | Mammalian sweet and amino acid heterodimeric taste receptors |
| ATE376146T1 (de) | 2001-08-31 | 2007-11-15 | Gentex Corp | Fahrzeuglampenanordnung mit kühlkörper |
| CN101006177B (zh) | 2002-03-15 | 2011-10-12 | 纽韦卢森公司 | 改善的用于合成模制分子的方法 |
| US20030215881A1 (en) | 2002-05-10 | 2003-11-20 | Hagan Bayley | Stochastic sensing through covalent interactions |
| US20040209299A1 (en) | 2003-03-07 | 2004-10-21 | Rubicon Genomics, Inc. | In vitro DNA immortalization and whole genome amplification using libraries generated from randomly fragmented DNA |
| AU2004225520A1 (en) | 2003-03-25 | 2004-10-14 | Stratagene | DNA polymerase fusions and uses thereof |
| US7163658B2 (en) | 2003-04-23 | 2007-01-16 | Rouvain Bension | Rapid sequencing of polymers |
| US7344882B2 (en) | 2003-05-12 | 2008-03-18 | Bristol-Myers Squibb Company | Polynucleotides encoding variants of the TRP channel family member, LTRPC3 |
| AU2003904237A0 (en) | 2003-08-08 | 2003-08-21 | Garvan Institute Of Medical Research | Novel translocation assay |
| WO2005056750A2 (en) | 2003-12-11 | 2005-06-23 | Quark Biotech, Inc. | Inversion-duplication of nucleic acids and libraries prepared thereby |
| WO2005076010A2 (en) | 2004-02-06 | 2005-08-18 | Council Of Scientific And Industrial Research | Computational method for identifying adhesin and adhesin-like proteins of therapeutic potential |
| JP2005253427A (ja) | 2004-03-15 | 2005-09-22 | Aisin Seiki Co Ltd | 核酸検出方法及び核酸単離方法 |
| US7238485B2 (en) | 2004-03-23 | 2007-07-03 | President And Fellows Of Harvard College | Methods and apparatus for characterizing polynucleotides |
| WO2005124888A1 (en) | 2004-06-08 | 2005-12-29 | President And Fellows Of Harvard College | Suspended carbon nanotube field effect transistor |
| US7972858B2 (en) | 2004-08-13 | 2011-07-05 | President And Fellows Of Harvard College | Ultra high-throughput opti-nanopore DNA readout platform |
| US20060105461A1 (en) | 2004-10-22 | 2006-05-18 | May Tom-Moy | Nanopore analysis system |
| US7867716B2 (en) | 2004-12-21 | 2011-01-11 | The Texas A&M University System | High temperature ion channels and pores |
| GB0505971D0 (en) | 2005-03-23 | 2005-04-27 | Isis Innovation | Delivery of molecules to a lipid bilayer |
| US7272518B2 (en) | 2005-07-01 | 2007-09-18 | Square D Company | Automated hierarchy classification in utility monitoring systems |
| WO2007024997A2 (en) | 2005-08-22 | 2007-03-01 | Fermalogic, Inc. | Methods of increasing production of secondary metabolites |
| US7877154B2 (en) | 2005-09-30 | 2011-01-25 | Fisher-Rosemount Systems, Inc. | Method and system for controlling a batch process |
| KR100730350B1 (ko) | 2005-10-17 | 2007-06-19 | 삼성전자주식회사 | 표면처리된 나노포어를 이용한 ｄｎａ 검출방법 및검출장치 |
| GB0523282D0 (en) | 2005-11-15 | 2005-12-21 | Isis Innovation | Methods using pores |
| WO2007075987A2 (en) | 2005-12-22 | 2007-07-05 | Pacific Biosciences Of California, Inc. | Active surface coupled polymerases |
| US7932029B1 (en) | 2006-01-04 | 2011-04-26 | Si Lok | Methods for nucleic acid mapping and identification of fine-structural-variations in nucleic acids and utilities |
| US7849581B2 (en) | 2006-05-05 | 2010-12-14 | University Of Utah Research Foundation | Nanopore electrode, nanopore membrane, methods of preparation and surface modification, and use thereof |
| WO2008030968A2 (en) | 2006-09-06 | 2008-03-13 | Phase Bioscience, Inc. | Fusion peptide therapeutic compositions |
| US7638034B2 (en) | 2006-09-21 | 2009-12-29 | Los Alamos National Security, Llc | Electrochemical detection of single molecules using abiotic nanopores having electrically tunable dimensions |
| WO2008045575A2 (en) | 2006-10-13 | 2008-04-17 | J. Craig Venter Institute, Inc. | Sequencing method |
| US8594848B2 (en) | 2006-11-28 | 2013-11-26 | Lester F. Ludwig | Reconfigurable chemical process systems |
| EP2122344B8 (en) | 2007-02-20 | 2019-08-21 | Oxford Nanopore Technologies Limited | Lipid bilayer sensor system |
| CA2684801C (en) | 2007-04-04 | 2017-10-10 | The Regents Of The University Of California | Compositions, devices, systems, and methods for using a nanopore |
| US8158344B2 (en) | 2007-06-29 | 2012-04-17 | Duke University | Methods and compositions for correlating genetic markers with multiple sclerosis |
| GB0716005D0 (en) | 2007-08-16 | 2007-09-26 | Imp Innovations Ltd | Single molecule spectroscopy using nanoporpus membranes |
| GB0716264D0 (en) | 2007-08-21 | 2007-09-26 | Isis Innovation | Bilayers |
| EP3540436B1 (en) | 2007-09-12 | 2023-11-01 | President And Fellows Of Harvard College | High-resolution molecular sensor |
| GB2453377A (en) | 2007-10-05 | 2009-04-08 | Isis Innovation | Transmembrane protein pores and molecular adapters therefore. |
| US8951731B2 (en) | 2007-10-15 | 2015-02-10 | Complete Genomics, Inc. | Sequence analysis using decorated nucleic acids |
| GB0724736D0 (en) | 2007-12-19 | 2008-01-30 | Oxford Nanolabs Ltd | Formation of layers of amphiphilic molecules |
| WO2009084721A1 (en) | 2007-12-31 | 2009-07-09 | Fujirebio Inc. | Clusters of microresonators for cavity mode optical sensing |
| US8231969B2 (en) | 2008-03-26 | 2012-07-31 | University Of Utah Research Foundation | Asymmetrically functionalized nanoparticles |
| CN104862383B (zh) | 2008-03-28 | 2019-05-28 | 加利福尼亚太平洋生物科学股份有限公司 | 用于核酸测序的组合物和方法 |
| EP2293921A4 (en) | 2008-05-22 | 2013-05-22 | Univ California | MEMBRANE PROBLEMS AND MEMBRANES MADE FROM THESE |
| US8652771B2 (en) | 2008-05-28 | 2014-02-18 | University of Souther California | Measurement of succinate in urine samples as a biomarker of kidney damage in diabetic subjects |
| WO2010004273A1 (en) | 2008-07-07 | 2010-01-14 | Oxford Nanopore Technologies Limited | Base-detecting pore |
| CN103695530B (zh) | 2008-07-07 | 2016-05-25 | 牛津纳米孔技术有限公司 | 酶-孔构建体 |
| EP2344891B1 (en) | 2008-09-22 | 2016-03-16 | University Of Washington | Msp nanopores and related methods |
| US9080211B2 (en) | 2008-10-24 | 2015-07-14 | Epicentre Technologies Corporation | Transposon end compositions and methods for modifying nucleic acids |
| GB0820927D0 (en) | 2008-11-14 | 2008-12-24 | Isis Innovation | Method |
| EP2359289A4 (en) | 2008-11-26 | 2015-11-11 | Illumina Inc | METHODS AND SYSTEMS FOR ANALYZING SEQUENCING DATA |
| AU2010209528B2 (en) | 2009-01-30 | 2015-10-01 | Oxford Nanopore Technologies Limited | Adaptors for nucleic acid constructs in transmembrane sequencing |
| EP2391655B1 (en) | 2009-01-30 | 2017-10-11 | Oxford Nanopore Technologies Limited | Hybridization linkers |
| CA2753294A1 (en) | 2009-02-23 | 2010-08-26 | Cytomx Therapeutics, Inc. | Proproteins and methods of use thereof |
| FR2943656A1 (fr) | 2009-03-25 | 2010-10-01 | Air Liquide | Procede et installation de production d'hydrogene mettant en oeuvre un compresseur thermocinetique |
| GB0905140D0 (en) | 2009-03-25 | 2009-05-06 | Isis Innovation | Method |
| AU2010240670B2 (en) | 2009-04-20 | 2015-08-20 | Oxford Nanopore Technologies Limited | Lipid bilayer sensor array |
| WO2011067559A1 (en) | 2009-12-01 | 2011-06-09 | Oxford Nanopore Technologies Limited | Biochemical analysis instrument |
| FR2955773B1 (fr) | 2010-02-01 | 2017-05-26 | Commissariat A L'energie Atomique | Complexe moleculaire de ciblage des antigenes vers les cellules presentatrices d'antigene et ses applications pour la vaccination |
| CA3116307C (en) | 2010-02-23 | 2023-10-17 | University Of Washington | Artificial mycolic acid membranes |
| EP2556085A2 (en) | 2010-04-05 | 2013-02-13 | Bar-Ilan University | Protease-activatable pore-forming polypeptides |
| CN103370617B (zh) | 2010-10-01 | 2015-11-25 | 牛津纳米孔技术有限公司 | 生物化学分析设备和旋转阀 |
| CN102116783B (zh) | 2010-12-31 | 2013-05-29 | 北京普源精电科技有限公司 | 一种波形显示方法 |
| GB201100516D0 (en) | 2011-01-12 | 2011-02-23 | Isis Innovation | Method using fluorinated amphiphiles |
| CN102174554A (zh) | 2011-01-24 | 2011-09-07 | 内蒙古民族大学 | 双控双调节原核表达载体系统及其构建方法和用途 |
| WO2012107778A2 (en) | 2011-02-11 | 2012-08-16 | Oxford Nanopore Technologies Limited | Mutant pores |
| WO2012164270A1 (en) | 2011-05-27 | 2012-12-06 | Oxford Nanopore Technologies Limited | Coupling method |
| WO2012166906A1 (en) | 2011-05-31 | 2012-12-06 | Massachusetts Institute Of Technology | Cell-directed synthesis of multifunctional nanopatterns and nanomaterials |
| AU2012288629B2 (en) | 2011-07-25 | 2017-02-02 | Oxford Nanopore Technologies Limited | Hairpin loop method for double strand polynucleotide sequencing using transmembrane pores |
| JP6457811B2 (ja) | 2011-09-23 | 2019-01-23 | オックスフォード ナノポール テクノロジーズ リミテッド | ポリマー単位を含むポリマーの解析 |
| US9758823B2 (en) | 2011-10-21 | 2017-09-12 | Oxford Nanopore Technologies Limited | Enzyme method |
| WO2013098561A1 (en) | 2011-12-29 | 2013-07-04 | Oxford Nanopore Technologies Limited | Method for characterising a polynucelotide by using a xpd helicase |
| US10385382B2 (en) | 2011-12-29 | 2019-08-20 | Oxford Nanopore Technologies Ltd. | Enzyme method |
| CN107828877A (zh) | 2012-01-20 | 2018-03-23 | 吉尼亚科技公司 | 基于纳米孔的分子检测与测序 |
| AU2013220156B2 (en) | 2012-02-15 | 2018-08-09 | Oxford Nanopore Technologies Limited | Aptamer method |
| EP2836506B1 (en) | 2012-04-10 | 2017-04-19 | Oxford Nanopore Technologies Limited | Mutant lysenin pores |
| TWI655213B (zh) | 2012-07-13 | 2019-04-01 | 目立康股份有限公司 | 自我組織化肽衍生物的製造方法 |
| US11155860B2 (en) | 2012-07-19 | 2021-10-26 | Oxford Nanopore Technologies Ltd. | SSB method |
| CA2879355C (en) | 2012-07-19 | 2021-09-21 | Oxford Nanopore Technologies Limited | Helicase construct and its use in characterising polynucleotides |
| CA2879261C (en) | 2012-07-19 | 2022-12-06 | Oxford Nanopore Technologies Limited | Modified helicases |
| WO2014064444A1 (en) | 2012-10-26 | 2014-05-01 | Oxford Nanopore Technologies Limited | Droplet interfaces |
| GB201313121D0 (en) | 2013-07-23 | 2013-09-04 | Oxford Nanopore Tech Ltd | Array of volumes of polar medium |
| US9683230B2 (en) | 2013-01-09 | 2017-06-20 | Illumina Cambridge Limited | Sample preparation on a solid support |
| US20140206842A1 (en) | 2013-01-22 | 2014-07-24 | Muhammed Majeed | Peptides Modified with Triterpenoids and Small Organic Molecules: Synthesis and use in Cosmeceutical |
| US10179933B2 (en) | 2013-02-07 | 2019-01-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Hybrid nanopores and uses thereof for detection of analytes |
| GB201314695D0 (en) | 2013-08-16 | 2013-10-02 | Oxford Nanopore Tech Ltd | Method |
| AU2014224432B2 (en) | 2013-03-08 | 2019-10-24 | Oxford Nanopore Technologies Limited | Enzyme stalling method |
| ES2724824T3 (es) | 2013-03-13 | 2019-09-16 | Illumina Inc | Métodos para la secuenciación de ácidos nucleicos |
| US10613076B2 (en) | 2013-03-14 | 2020-04-07 | The Trustees Of Boston University | Optoelectronic control of solid-state nanopores |
| GB201313477D0 (en) | 2013-07-29 | 2013-09-11 | Univ Leuven Kath | Nanopore biosensors for detection of proteins and nucleic acids |
| DK3004378T3 (en) | 2013-05-24 | 2018-03-26 | Illumina Cambridge Ltd | Pyrophosphorolytic sequencing using nanopores |
| WO2015051378A1 (en) | 2013-10-04 | 2015-04-09 | University Of Washington Through Its Center For Commercialization | Systems and methods for nanopore-based analysis of nucleic acids |
| CN105899678A (zh) | 2013-10-18 | 2016-08-24 | 牛津纳米孔技术公司 | 经修饰的酶 |
| GB201406151D0 (en) | 2014-04-04 | 2014-05-21 | Oxford Nanopore Tech Ltd | Method |
| CN105934522B (zh) | 2013-11-26 | 2021-07-20 | 伊鲁米那股份有限公司 | 用于多核苷酸测序的组合物和方法 |
| WO2015097289A1 (en) | 2013-12-24 | 2015-07-02 | Vib Vzw | Secretion and functional display of chimeric polypeptides |
| AU2015208919B9 (en) | 2014-01-22 | 2021-04-01 | Oxford Nanopore Technologies Limited | Method for attaching one or more polynucleotide binding proteins to a target polynucleotide |
| GB201406155D0 (en) | 2014-04-04 | 2014-05-21 | Oxford Nanopore Tech Ltd | Method |
| GB201403096D0 (en) | 2014-02-21 | 2014-04-09 | Oxford Nanopore Tech Ltd | Sample preparation method |
| US10337060B2 (en) | 2014-04-04 | 2019-07-02 | Oxford Nanopore Technologies Ltd. | Method for characterising a double stranded nucleic acid using a nano-pore and anchor molecules at both ends of said nucleic acid |
| EP3137490B1 (en) | 2014-05-02 | 2021-01-27 | Oxford Nanopore Technologies Limited | Mutant pores |
| FR3023394B1 (fr) | 2014-07-02 | 2017-12-29 | Adn Access Data Networks | Dispositif permettant de faciliter l'enseignement de la langue amharique et d'en normaliser l'ecriture |
| KR20170042794A (ko) | 2014-09-01 | 2017-04-19 | 브이아이비 브이지더블유 | 돌연변이체 csgg 포어 |
| US10266885B2 (en) | 2014-10-07 | 2019-04-23 | Oxford Nanopore Technologies Ltd. | Mutant pores |
| GB201502809D0 (en) | 2015-02-19 | 2015-04-08 | Oxford Nanopore Tech Ltd | Mutant pore |
| GB201502810D0 (en) | 2015-02-19 | 2015-04-08 | Oxford Nanopore Tech Ltd | Method |
| US11169138B2 (en) | 2015-04-14 | 2021-11-09 | Katholieke Universiteit Leuven | Nanopores with internal protein adaptors |
| EP3387432B1 (en) | 2015-12-08 | 2022-09-28 | Katholieke Universiteit Leuven KU Leuven Research & Development | Modified nanopores, compositions comprising the same, and uses thereof |
| KR102222188B1 (ko) | 2016-03-02 | 2021-03-02 | 옥스포드 나노포어 테크놀로지즈 리미티드 | 돌연변이체 기공 |
| EP4122949B1 (en) | 2016-04-06 | 2024-06-05 | Oxford Nanopore Technologies plc | Mutant pore |
| GB201707122D0 (en) | 2017-05-04 | 2017-06-21 | Oxford Nanopore Tech Ltd | Pore |
| EP3645552B1 (en) | 2017-06-30 | 2023-06-28 | Vib Vzw | Novel protein pores |
-
2013
- 2013-03-15 EP EP13711464.1A patent/EP2836506B1/en active Active
- 2013-03-15 CN CN201380030527.2A patent/CN104350067A/zh active Pending
- 2013-03-15 EP EP17157441.1A patent/EP3192804B1/en active Active
- 2013-03-15 JP JP2015505016A patent/JP6271505B2/ja active Active
- 2013-03-15 CN CN202011579254.5A patent/CN112646019B/zh active Active
- 2013-03-15 BR BR112014025157-6A patent/BR112014025157B1/pt active IP Right Grant
- 2013-03-15 KR KR1020147031143A patent/KR102083695B1/ko active IP Right Grant
- 2013-03-15 WO PCT/GB2013/050667 patent/WO2013153359A1/en active Application Filing
- 2013-03-15 AU AU2013246702A patent/AU2013246702B2/en active Active
- 2013-03-15 US US14/391,660 patent/US9777049B2/en active Active
- 2013-03-15 CA CA2869546A patent/CA2869546C/en active Active
-
2017
- 2017-08-31 US US15/692,498 patent/US10882889B2/en active Active
- 2017-12-27 JP JP2017250647A patent/JP2018075025A/ja active Pending
-
2020
- 2020-12-01 US US17/108,536 patent/US11845780B2/en active Active
-
2023
- 2023-11-08 US US18/504,590 patent/US20240199711A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP2836506B1 (en) | 2017-04-19 |
| CN104350067A (zh) | 2015-02-11 |
| EP3192804B1 (en) | 2019-08-28 |
| US20240199711A1 (en) | 2024-06-20 |
| JP2015514128A (ja) | 2015-05-18 |
| US20180208632A1 (en) | 2018-07-26 |
| EP3192804A1 (en) | 2017-07-19 |
| KR20150003272A (ko) | 2015-01-08 |
| EP2836506A1 (en) | 2015-02-18 |
| CA2869546A1 (en) | 2013-10-17 |
| US11845780B2 (en) | 2023-12-19 |
| CN112646019A (zh) | 2021-04-13 |
| CA2869546C (en) | 2020-07-21 |
| US10882889B2 (en) | 2021-01-05 |
| JP6271505B2 (ja) | 2018-01-31 |
| KR102083695B1 (ko) | 2020-03-02 |
| BR112014025157B1 (pt) | 2022-02-08 |
| WO2013153359A1 (en) | 2013-10-17 |
| AU2013246702B2 (en) | 2017-06-15 |
| JP2018075025A (ja) | 2018-05-17 |
| US9777049B2 (en) | 2017-10-03 |
| US20210324020A1 (en) | 2021-10-21 |
| AU2013246702A1 (en) | 2014-10-16 |
| US20150068904A1 (en) | 2015-03-12 |
| BR112014025157A2 (pt) | 2018-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112646019B (zh) | 突变胞溶素孔 | |
| CN108699138B (zh) | 突变孔 | |
| CN106459159B (zh) | 突变孔 | |
| JP7364333B2 (ja) | 変異体ポア | |
| JP6169976B2 (ja) | 変異体細孔 | |
| CN104126018B (zh) | 酶方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: oxford Applicant after: Oxford nanopore Technology Public Co.,Ltd. Address before: Oxfordshire Applicant before: OXFORD NANOPORE TECHNOLOGIES LTD. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |