JP5926693B2 - ペプチドの濃度を決定する方法 - Google Patents
ペプチドの濃度を決定する方法 Download PDFInfo
- Publication number
- JP5926693B2 JP5926693B2 JP2012556416A JP2012556416A JP5926693B2 JP 5926693 B2 JP5926693 B2 JP 5926693B2 JP 2012556416 A JP2012556416 A JP 2012556416A JP 2012556416 A JP2012556416 A JP 2012556416A JP 5926693 B2 JP5926693 B2 JP 5926693B2
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- tag
- internal
- standard
- mixture
- 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
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 1024
- 238000000034 method Methods 0.000 title claims description 137
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 383
- 229920001184 polypeptide Polymers 0.000 claims description 262
- 239000000203 mixture Substances 0.000 claims description 235
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 70
- 238000003776 cleavage reaction Methods 0.000 claims description 64
- 230000007062 hydrolysis Effects 0.000 claims description 62
- 238000006460 hydrolysis reaction Methods 0.000 claims description 62
- 230000007017 scission Effects 0.000 claims description 55
- 239000011541 reaction mixture Substances 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 102000035195 Peptidases Human genes 0.000 claims description 28
- 108091005804 Peptidases Proteins 0.000 claims description 28
- 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 claims description 26
- AUTOLBMXDDTRRT-JGVFFNPUSA-N (4R,5S)-dethiobiotin Chemical compound C[C@@H]1NC(=O)N[C@@H]1CCCCCC(O)=O AUTOLBMXDDTRRT-JGVFFNPUSA-N 0.000 claims description 26
- FBTSQILOGYXGMD-LURJTMIESA-N 3-nitro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 claims description 21
- 238000004949 mass spectrometry Methods 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 20
- 230000002255 enzymatic effect Effects 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 15
- 229960002685 biotin Drugs 0.000 claims description 13
- 235000020958 biotin Nutrition 0.000 claims description 13
- 239000011616 biotin Substances 0.000 claims description 13
- 108090001008 Avidin Proteins 0.000 claims description 8
- 108010090804 Streptavidin Proteins 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 6
- 125000003636 chemical group Chemical group 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 4
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 claims description 4
- 238000011002 quantification Methods 0.000 description 59
- 125000000539 amino acid group Chemical group 0.000 description 48
- 235000001014 amino acid Nutrition 0.000 description 34
- 150000001413 amino acids Chemical class 0.000 description 34
- 241000894007 species Species 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 31
- -1 cyanogen halide Chemical class 0.000 description 30
- 238000010168 coupling process Methods 0.000 description 24
- 108090000631 Trypsin Proteins 0.000 description 23
- 102000004142 Trypsin Human genes 0.000 description 23
- 230000008878 coupling Effects 0.000 description 23
- 238000005859 coupling reaction Methods 0.000 description 23
- 102000004169 proteins and genes Human genes 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 238000000926 separation method Methods 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 125000005647 linker group Chemical group 0.000 description 17
- 239000000758 substrate Substances 0.000 description 16
- 210000004899 c-terminal region Anatomy 0.000 description 15
- 238000010586 diagram Methods 0.000 description 15
- 238000010647 peptide synthesis reaction Methods 0.000 description 15
- 150000007970 thio esters Chemical class 0.000 description 15
- 239000004365 Protease Substances 0.000 description 14
- 238000001514 detection method Methods 0.000 description 14
- 238000005194 fractionation Methods 0.000 description 14
- 235000019419 proteases Nutrition 0.000 description 14
- 239000012588 trypsin Substances 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 239000007850 fluorescent dye Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 150000003573 thiols Chemical class 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 230000000155 isotopic effect Effects 0.000 description 10
- 230000027455 binding Effects 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- 239000012472 biological sample Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000006062 fragmentation reaction Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 238000004811 liquid chromatography Methods 0.000 description 8
- 239000006166 lysate Substances 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000013467 fragmentation Methods 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- FRJNIHLOMXIQKH-UHFFFAOYSA-N 1-amino-15-oxo-4,7,10-trioxa-14-azaoctadecan-18-oic acid Chemical group NCCCOCCOCCOCCCNC(=O)CCC(O)=O FRJNIHLOMXIQKH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical class [H]O* 0.000 description 6
- 150000005002 naphthylamines Chemical class 0.000 description 6
- 150000002989 phenols Chemical class 0.000 description 6
- 229920000570 polyether Polymers 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 5
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 150000003568 thioethers Chemical class 0.000 description 5
- 238000000825 ultraviolet detection Methods 0.000 description 5
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 150000008574 D-amino acids Chemical group 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000004952 Polyamide Substances 0.000 description 4
- 229920001273 Polyhydroxy acid Polymers 0.000 description 4
- 239000004642 Polyimide Substances 0.000 description 4
- 101710118538 Protease Proteins 0.000 description 4
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 150000004982 aromatic amines Chemical class 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 210000001124 body fluid Anatomy 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000002427 irreversible effect Effects 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 229920002492 poly(sulfone) Polymers 0.000 description 4
- 229920002647 polyamide Polymers 0.000 description 4
- 239000004417 polycarbonate Substances 0.000 description 4
- 229920000515 polycarbonate Polymers 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 229920001721 polyimide Polymers 0.000 description 4
- 229920002635 polyurethane Polymers 0.000 description 4
- 239000004814 polyurethane Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 3
- 239000004721 Polyphenylene oxide Substances 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000005417 aminobenzoic acid derivatives Chemical class 0.000 description 3
- 150000003931 anilides Chemical class 0.000 description 3
- 150000001448 anilines Chemical class 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 150000001576 beta-amino acids Chemical group 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000001360 collision-induced dissociation Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000000105 evaporative light scattering detection Methods 0.000 description 3
- 238000001917 fluorescence detection Methods 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- 150000007857 hydrazones Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000002331 protein detection Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 150000003334 secondary amides Chemical class 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 150000003511 tertiary amides Chemical class 0.000 description 3
- 125000005000 thioaryl group Chemical group 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical group N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 108090000787 Subtilisin Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 150000008430 aromatic amides Chemical class 0.000 description 2
- 125000003828 azulenyl group Chemical group 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 238000001818 capillary gel electrophoresis Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 description 2
- 238000001211 electron capture detection Methods 0.000 description 2
- 238000001077 electron transfer detection Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 150000003977 halocarboxylic acids Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 125000003427 indacenyl group Chemical group 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 229920001451 polypropylene glycol Chemical group 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011946 reduction process Methods 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 150000003557 thiazoles Chemical class 0.000 description 2
- 150000003556 thioamides Chemical class 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 description 1
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 description 1
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 description 1
- 150000000179 1,2-aminoalcohols Chemical class 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- PWGJDPKCLMLPJW-UHFFFAOYSA-N 1,8-diaminooctane Chemical compound NCCCCCCCCN PWGJDPKCLMLPJW-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- PVYYBLWTZMRIIY-UHFFFAOYSA-N 2,3,4a,8a-tetrahydro-1h-quinazolin-4-one Chemical class C1=CC=CC2C(=O)NCNC21 PVYYBLWTZMRIIY-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- DYNFCHNNOHNJFG-UHFFFAOYSA-N 2-formylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C=O DYNFCHNNOHNJFG-UHFFFAOYSA-N 0.000 description 1
- YOOSAIJKYCBPFW-UHFFFAOYSA-N 3-[4-(3-aminopropoxy)butoxy]propan-1-amine Chemical compound NCCCOCCCCOCCCN YOOSAIJKYCBPFW-UHFFFAOYSA-N 0.000 description 1
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 1
- PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 description 1
- PCNFLKVWBDNNOW-UHFFFAOYSA-N 4-hydrazinylbenzoic acid Chemical compound NNC1=CC=C(C(O)=O)C=C1 PCNFLKVWBDNNOW-UHFFFAOYSA-N 0.000 description 1
- HSOHRNOQOMBXFS-UHFFFAOYSA-N 4-oxo-4-thionitrosobutanoic acid Chemical compound OC(=O)CCC(=O)N=S HSOHRNOQOMBXFS-UHFFFAOYSA-N 0.000 description 1
- DEQPBRIACBATHE-FXQIFTODSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-2-iminopentanoic acid Chemical compound N1C(=O)N[C@@H]2[C@H](CCCC(=N)C(=O)O)SC[C@@H]21 DEQPBRIACBATHE-FXQIFTODSA-N 0.000 description 1
- CSEAKGXTWOWTOQ-UHFFFAOYSA-N 5-hydrazinyl-5-oxopentanoic acid Chemical compound NNC(=O)CCCC(O)=O CSEAKGXTWOWTOQ-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 150000007650 D alpha amino acids Chemical group 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 239000012988 Dithioester Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Chemical group 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 150000007649 L alpha amino acids Chemical group 0.000 description 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical group C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 102000056251 Prolyl Oligopeptidases Human genes 0.000 description 1
- 101710178372 Prolyl endopeptidase Chemical group 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Chemical group C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001294 alanine derivatives Chemical class 0.000 description 1
- 150000008431 aliphatic amides Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000005022 dithioester group Chemical group 0.000 description 1
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940040102 levulinic acid Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 229930182817 methionine Chemical group 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000002917 oxazolidines Chemical class 0.000 description 1
- 238000006400 oxidative hydrolysis reaction Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 125000001828 phenalenyl group Chemical group C1(C=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 150000004986 phenylenediamines Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004094 preconcentration Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229920013730 reactive polymer Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000446 sulfanediyl group Chemical class *S* 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003548 thiazolidines Chemical class 0.000 description 1
- 150000003583 thiosemicarbazides Chemical class 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical group OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6848—Methods of protein analysis involving mass spectrometry
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2/00—Peptides of undefined number of amino acids; Derivatives thereof
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
- G01N2458/15—Non-radioactive isotope labels, e.g. for detection by mass spectrometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2560/00—Chemical aspects of mass spectrometric analysis of biological material
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Genetics & Genomics (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10002664.0 | 2010-03-12 | ||
| EP10002664 | 2010-03-12 | ||
| PCT/EP2011/001167 WO2011110341A1 (en) | 2010-03-12 | 2011-03-09 | Method for determining the concentration of a peptide |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016000283A Division JP6186017B2 (ja) | 2010-03-12 | 2016-01-04 | ペプチドの濃度を決定する方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013522174A JP2013522174A (ja) | 2013-06-13 |
| JP2013522174A5 JP2013522174A5 (OSRAM) | 2014-04-24 |
| JP5926693B2 true JP5926693B2 (ja) | 2016-05-25 |
Family
ID=44022936
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012556416A Active JP5926693B2 (ja) | 2010-03-12 | 2011-03-09 | ペプチドの濃度を決定する方法 |
| JP2016000283A Active JP6186017B2 (ja) | 2010-03-12 | 2016-01-04 | ペプチドの濃度を決定する方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016000283A Active JP6186017B2 (ja) | 2010-03-12 | 2016-01-04 | ペプチドの濃度を決定する方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US20130095514A1 (OSRAM) |
| EP (1) | EP2545384B1 (OSRAM) |
| JP (2) | JP5926693B2 (OSRAM) |
| WO (1) | WO2011110341A1 (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016032319A1 (en) * | 2014-08-28 | 2016-03-03 | Erasmus University Medical Center Rotterdam | Protein quantitation with mass spectrometry. |
| CN108802162B (zh) * | 2016-11-25 | 2020-08-18 | 北京毅新博创生物科技有限公司 | 通过内部标准物质谱检测微生物的方法 |
| WO2019232520A1 (en) * | 2018-06-01 | 2019-12-05 | Cerno Bioscience Llc | Mass spectral analysis of large molecules |
| KR102674098B1 (ko) * | 2021-01-14 | 2024-06-12 | (주)옵토레인 | 스위칭 펩티드 및 이를 이용한 멀티플렉스 면역분석 방법 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6040423A (en) | 1990-08-31 | 2000-03-21 | Gsellschaft Fur Biotechnologische Forschung Mbh (Gbf) | Process for synthesis of peptides |
| US6117635A (en) * | 1996-07-16 | 2000-09-12 | Intergen Company | Nucleic acid amplification oligonucleotides with molecular energy transfer labels and methods based thereon |
| US7045296B2 (en) * | 2001-05-08 | 2006-05-16 | Applera Corporation | Process for analyzing protein samples |
| WO2003016861A2 (en) | 2001-08-14 | 2003-02-27 | President And Fellows Of Harvard College | Absolute quantification of proteins and modified forms thereof by multistage mass spectrometry |
| US20040033530A1 (en) * | 2002-04-08 | 2004-02-19 | Awrey Donald E. | High throughput purification, characterization and identification of recombinant proteins |
| WO2003102220A2 (en) * | 2002-06-04 | 2003-12-11 | The Institute For Systems Biology | Methods for high throughput and quantitative proteome analysis |
| US20060062531A1 (en) * | 2004-09-17 | 2006-03-23 | Stephen Turner | Fabrication of optical confinements |
| JP2006300758A (ja) * | 2005-04-21 | 2006-11-02 | Apro Life Science Institute Inc | 内部標準ペプチドを用いて生体由来試料に含まれる標的タンパク質を定量する方法 |
| DE602005004902T2 (de) * | 2005-06-02 | 2008-10-16 | Entelechon Gmbh | Künstliches Protein, Verfahren für absolute Quantifizierung der Proteine und seine Benutzung |
| US8076074B2 (en) * | 2005-11-29 | 2011-12-13 | Quest Diagnostics Investments Incorporated | Balanced translocation in comparative hybridization |
| EP2124060A1 (en) * | 2008-05-23 | 2009-11-25 | ETH Zurich | Method for high throughput peptide/protein assay generation and assays generated therewith |
| GB0809488D0 (en) * | 2008-05-23 | 2008-07-02 | Electrophoretics Ltd | Mass spectrometric analysis |
-
2011
- 2011-03-09 US US13/634,197 patent/US20130095514A1/en not_active Abandoned
- 2011-03-09 EP EP11707354.4A patent/EP2545384B1/en active Active
- 2011-03-09 WO PCT/EP2011/001167 patent/WO2011110341A1/en not_active Ceased
- 2011-03-09 JP JP2012556416A patent/JP5926693B2/ja active Active
-
2016
- 2016-01-04 JP JP2016000283A patent/JP6186017B2/ja active Active
- 2016-03-18 US US15/074,214 patent/US20160223562A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20130095514A1 (en) | 2013-04-18 |
| JP2016128812A (ja) | 2016-07-14 |
| JP2013522174A (ja) | 2013-06-13 |
| EP2545384B1 (en) | 2017-12-13 |
| US20160223562A1 (en) | 2016-08-04 |
| JP6186017B2 (ja) | 2017-08-23 |
| WO2011110341A1 (en) | 2011-09-15 |
| EP2545384A1 (en) | 2013-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002341862C1 (en) | Controlling isotope effects during fractionation of analytes | |
| AU2002303760B2 (en) | Methods for isolating and labeling sample molecules | |
| CN101600959B (zh) | 肽和蛋白的定量方法 | |
| JP4300029B2 (ja) | ゲルフリー定性及び定量的プロテオーム分析のための方法及び装置、ならびにその使用 | |
| JP5317336B2 (ja) | 質量分析装置を用いたタンパク質定量のための評価用ペプチド、人工標準タンパク質、及びタンパク質の定量方法 | |
| Jones | Amino acid analysis by o-phthaldialdehyde precolumn derivatization and reverse-phase HPLC | |
| AU2002303760A1 (en) | Methods for isolating and labeling sample molecules | |
| JP6186017B2 (ja) | ペプチドの濃度を決定する方法 | |
| CA2443515C (en) | Methods and kits useful for the simplification of complex peptide mixtures | |
| AU2002256060A1 (en) | Methods and kits useful for the simplification of complex peptide mixtures | |
| Tai et al. | Non-targeted identification of D-amino acid-containing peptides through enzymatic screening, chiral amino acid analysis, and LC-MS | |
| Drǎguşanu et al. | Epitope motif of an anti‐nitrotyrosine antibody specific for tyrosine‐nitrated peptides revealed by a combination of affinity approaches and mass spectrometry | |
| NZ529987A (en) | Characterising polypeptides which includes the use of a lysine selective agent, amine reactive agent and recovering N-terminal peptide fragments | |
| US20060134691A1 (en) | Labeling methodology comprising oligopeptides | |
| JP4558297B2 (ja) | 発現微量タンパク質／ペプチドの検出・分離・同定法 | |
| Gu et al. | Precise proteomic identification using mass spectrometry coupled with stable isotope labeling | |
| Leitner | Chemical derivatization of peptides for quantitative proteomics | |
| Regnier | An isotope coding strategy for proteomics involving both amine and carboxyl group labeling | |
| WO2003102022A1 (en) | Use of reagent homologs for comparative proteomics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140306 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140306 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150421 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150716 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150805 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150901 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160104 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160222 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160405 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160422 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5926693 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |