JP2012502011A

JP2012502011A - 増加した安定性を有する成長ホルモンコンジュゲート

増加した安定性を有する成長ホルモンコンジュゲート Download PDF

Info

Publication number: JP2012502011A
Authority: JP; Japan
Prior art keywords: compound; growth hormone; group; peptide; compound according
Prior art date: 2008-09-09
Legal status : Withdrawn

Application number

JP2011525575A

Other languages

English (en)

Japanese (ja)

Other versions

JP2012502011A5 (https=

Inventor

ニルス・ランゲラン・ヨハンセン

Original Assignee

ノヴォ・ノルディスク・ヘルス・ケア・アーゲー

Priority date

2008-09-09

Filing date

2009-09-09

Publication date

2012-01-26

2009-09-09 Application filed by ノヴォ・ノルディスク・ヘルス・ケア・アーゲー filed Critical ノヴォ・ノルディスク・ヘルス・ケア・アーゲー

2012-01-26 Publication of JP2012502011A publication Critical patent/JP2012502011A/ja

2012-10-25 Publication of JP2012502011A5 publication Critical patent/JP2012502011A5/ja

Status Withdrawn legal-status Critical Current

Links

108010051696 Growth Hormone Proteins 0.000 title claims abstract description 134
239000000122 growth hormone Substances 0.000 title claims abstract description 133
102000018997 Growth Hormone Human genes 0.000 title claims abstract description 132
150000001875 compounds Chemical class 0.000 claims abstract description 291
238000000034 method Methods 0.000 claims abstract description 87
102100020948 Growth hormone receptor Human genes 0.000 claims abstract description 78
108010033419 somatotropin-binding protein Proteins 0.000 claims abstract description 71
108090000765 processed proteins & peptides Proteins 0.000 claims description 113
125000000524 functional group Chemical group 0.000 claims description 43
125000000732 arylene group Chemical group 0.000 claims description 40
108060008539 Transglutaminase Proteins 0.000 claims description 39
102000003601 transglutaminase Human genes 0.000 claims description 39
125000005549 heteroarylene group Chemical group 0.000 claims description 36
125000003118 aryl group Chemical group 0.000 claims description 32
-1 phenylhydrazone Chemical class 0.000 claims description 32
150000001299 aldehydes Chemical class 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 26
125000005647 linker group Chemical group 0.000 claims description 20
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
102000004190 Enzymes Human genes 0.000 claims description 18
108090000790 Enzymes Proteins 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
125000000539 amino acid group Chemical group 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 14
239000008194 pharmaceutical composition Substances 0.000 claims description 14
150000002576 ketones Chemical class 0.000 claims description 13
230000004048 modification Effects 0.000 claims description 13
238000012986 modification Methods 0.000 claims description 13
230000000051 modifying effect Effects 0.000 claims description 13
150000007523 nucleic acids Chemical class 0.000 claims description 13
201000010099 disease Diseases 0.000 claims description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
125000003277 amino group Chemical group 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
239000012634 fragment Substances 0.000 claims description 9
150000002466 imines Chemical class 0.000 claims description 9
102000037865 fusion proteins Human genes 0.000 claims description 8
108020001507 fusion proteins Proteins 0.000 claims description 8
230000003054 hormonal effect Effects 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
108020004707 nucleic acids Proteins 0.000 claims description 8
102000039446 nucleic acids Human genes 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
125000006850 spacer group Chemical group 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 7
239000003638 chemical reducing agent Substances 0.000 claims description 7
125000005241 heteroarylamino group Chemical group 0.000 claims description 6
108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
230000001268 conjugating effect Effects 0.000 claims description 5
150000002374 hemiaminals Chemical class 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
238000003259 recombinant expression Methods 0.000 claims description 5
150000002923 oximes Chemical class 0.000 claims description 4
150000003852 triazoles Chemical class 0.000 claims description 4
230000012010 growth Effects 0.000 claims description 3
150000007857 hydrazones Chemical class 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
150000007659 semicarbazones Chemical class 0.000 claims description 3
229940126062 Compound A Drugs 0.000 claims description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 2
230000003213 activating effect Effects 0.000 claims description 2
230000008901 benefit Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
102000036124 hormone binding proteins Human genes 0.000 claims 1
108091011044 hormone binding proteins Proteins 0.000 claims 1
125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
102000004169 proteins and genes Human genes 0.000 abstract description 37
108090000623 proteins and genes Proteins 0.000 abstract description 37
230000021615 conjugation Effects 0.000 abstract description 14
238000001727 in vivo Methods 0.000 abstract description 10
238000001212 derivatisation Methods 0.000 abstract description 7
230000000144 pharmacologic effect Effects 0.000 abstract description 7
239000004365 Protease Substances 0.000 abstract description 6
230000001225 therapeutic effect Effects 0.000 abstract description 5
102000009027 Albumins Human genes 0.000 abstract description 3
108010088751 Albumins Proteins 0.000 abstract description 3
108091005804 Peptidases Proteins 0.000 abstract description 3
230000013878 renal filtration Effects 0.000 abstract description 3
230000005923 long-lasting effect Effects 0.000 abstract description 2
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract 1
102000002265 Human Growth Hormone Human genes 0.000 description 46
108010000521 Human Growth Hormone Proteins 0.000 description 46
239000000854 Human Growth Hormone Substances 0.000 description 46
235000018102 proteins Nutrition 0.000 description 36
239000000203 mixture Substances 0.000 description 33
235000001014 amino acid Nutrition 0.000 description 32
239000000872 buffer Substances 0.000 description 31
150000001413 amino acids Chemical class 0.000 description 30
229940024606 amino acid Drugs 0.000 description 29
239000000243 solution Substances 0.000 description 27
125000003275 alpha amino acid group Chemical group 0.000 description 26
102000004196 processed proteins & peptides Human genes 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
229920001223 polyethylene glycol Polymers 0.000 description 18
210000004027 cell Anatomy 0.000 description 17
229940088598 enzyme Drugs 0.000 description 17
238000006467 substitution reaction Methods 0.000 description 17
239000002202 Polyethylene glycol Substances 0.000 description 16
230000000694 effects Effects 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
150000003839 salts Chemical class 0.000 description 13
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 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 10
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
230000000813 microbial effect Effects 0.000 description 10
239000000047 product Substances 0.000 description 10
150000001345 alkine derivatives Chemical class 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
239000007951 isotonicity adjuster Substances 0.000 description 9
239000011159 matrix material Substances 0.000 description 9
230000001404 mediated effect Effects 0.000 description 9
229920001184 polypeptide Polymers 0.000 description 9
239000003755 preservative agent Substances 0.000 description 9
239000011347 resin Substances 0.000 description 9
229920005989 resin Polymers 0.000 description 9
239000000126 substance Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 8
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 8
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 8
230000003647 oxidation Effects 0.000 description 8
238000007254 oxidation reaction Methods 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
108010005843 Cysteine Proteases Proteins 0.000 description 7
102000005927 Cysteine Proteases Human genes 0.000 description 7
102000012479 Serine Proteases Human genes 0.000 description 7
108010022999 Serine Proteases Proteins 0.000 description 7
239000002253 acid Substances 0.000 description 7
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
150000005846 sugar alcohols Chemical class 0.000 description 7
102000005572 Cathepsin A Human genes 0.000 description 6
108010059081 Cathepsin A Proteins 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 6
239000004472 Lysine Substances 0.000 description 6
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
230000005847 immunogenicity Effects 0.000 description 6
230000002335 preservative effect Effects 0.000 description 6
238000006268 reductive amination reaction Methods 0.000 description 6
235000000346 sugar Nutrition 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
WHUUTDBJXJRKMK-VKHMYHEASA-N L-Glutamic acid Natural products OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
235000004279 alanine Nutrition 0.000 description 5
229960004050 aminobenzoic acid Drugs 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
125000000753 cycloalkyl group Chemical group 0.000 description 5
235000018417 cysteine Nutrition 0.000 description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000012038 nucleophile Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000000758 substrate Substances 0.000 description 5
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 4
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 4
239000004475 Arginine Substances 0.000 description 4
239000004215 Carbon black (E152) Substances 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
239000004471 Glycine Substances 0.000 description 4
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-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
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
238000012300 Sequence Analysis Methods 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
108010068542 Somatotropin Receptors Proteins 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
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
150000001335 aliphatic alkanes Chemical class 0.000 description 4
150000001336 alkenes Chemical class 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
230000009286 beneficial effect Effects 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
230000037396 body weight Effects 0.000 description 4
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
125000003636 chemical group Chemical group 0.000 description 4
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
150000004676 glycans Chemical group 0.000 description 4
125000001072 heteroaryl group Chemical group 0.000 description 4
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
150000002430 hydrocarbons Chemical class 0.000 description 4
230000002209 hydrophobic effect Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
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 4
DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
235000019799 monosodium phosphate Nutrition 0.000 description 4
150000002825 nitriles Chemical class 0.000 description 4
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 4
230000008569 process Effects 0.000 description 4
125000005551 pyridylene group Chemical group 0.000 description 4
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 4
229910000162 sodium phosphate Inorganic materials 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
108090000317 Chymotrypsin Proteins 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
206010056438 Growth hormone deficiency Diseases 0.000 description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
108090000526 Papain Proteins 0.000 description 3
208000020221 Short stature Diseases 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
108090000251 Sortase B Proteins 0.000 description 3
241001495137 Streptomyces mobaraensis Species 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
108090000631 Trypsin Proteins 0.000 description 3
102000004142 Trypsin Human genes 0.000 description 3
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
238000013459 approach Methods 0.000 description 3
235000009582 asparagine Nutrition 0.000 description 3
229960001230 asparagine Drugs 0.000 description 3
235000003704 aspartic acid Nutrition 0.000 description 3
238000003556 assay Methods 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
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 3
230000015572 biosynthetic process Effects 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
229960002376 chymotrypsin Drugs 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940126214 compound 3 Drugs 0.000 description 3
238000004590 computer program Methods 0.000 description 3
229910000397 disodium phosphate Inorganic materials 0.000 description 3
235000019800 disodium phosphate Nutrition 0.000 description 3
239000003814 drug Substances 0.000 description 3
238000005516 engineering process Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
230000004927 fusion Effects 0.000 description 3
229960003692 gamma aminobutyric acid Drugs 0.000 description 3
125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000004255 ion exchange chromatography Methods 0.000 description 3
229960000310 isoleucine Drugs 0.000 description 3
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
210000003127 knee Anatomy 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 3
239000002609 medium Substances 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
239000000178 monomer Substances 0.000 description 3
210000003205 muscle Anatomy 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
229940055729 papain Drugs 0.000 description 3
235000019834 papain Nutrition 0.000 description 3
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
238000005932 reductive alkylation reaction Methods 0.000 description 3
125000006413 ring segment Chemical group 0.000 description 3
108090000250 sortase A Proteins 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
238000001356 surgical procedure Methods 0.000 description 3
238000005891 transamination reaction Methods 0.000 description 3
239000012588 trypsin Substances 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
0 ***C(CC(*)**)=N Chemical compound ***C(CC(*)**)=N 0.000 description 2
UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 description 2
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 2
RDFMDVXONNIGBC-UHFFFAOYSA-N 2-aminoheptanoic acid Chemical compound CCCCCC(N)C(O)=O RDFMDVXONNIGBC-UHFFFAOYSA-N 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
CZUGFKJYCPYHHV-UHFFFAOYSA-N 3-methylthiopropanol Chemical compound CSCCCO CZUGFKJYCPYHHV-UHFFFAOYSA-N 0.000 description 2
CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 2
SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
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 2
108010013369 Enteropeptidase Proteins 0.000 description 2
102100029727 Enteropeptidase Human genes 0.000 description 2
108010071289 Factor XIII Proteins 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
206010017076 Fracture Diseases 0.000 description 2
108010015133 Galactose oxidase Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
101710099093 Growth hormone receptor Proteins 0.000 description 2
206010053759 Growth retardation Diseases 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
108010002386 Interleukin-3 Proteins 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
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 2
SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
208000001132 Osteoporosis Diseases 0.000 description 2
102000035195 Peptidases Human genes 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
201000010769 Prader-Willi syndrome Diseases 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
108700039882 Protein Glutamine gamma Glutamyltransferase 2 Proteins 0.000 description 2
102100038095 Protein-glutamine gamma-glutamyltransferase 2 Human genes 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
208000026928 Turner syndrome Diseases 0.000 description 2
HSCJRCZFDFQWRP-ABVWGUQPSA-N UDP-alpha-D-galactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-ABVWGUQPSA-N 0.000 description 2
HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
150000001241 acetals Chemical class 0.000 description 2
230000009471 action Effects 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000000996 additive effect Effects 0.000 description 2
238000012867 alanine scanning Methods 0.000 description 2
125000004450 alkenylene group Chemical group 0.000 description 2
125000004419 alkynylene group Chemical group 0.000 description 2
QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
229940009098 aspartate Drugs 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
229940000635 beta-alanine Drugs 0.000 description 2
239000012620 biological material Substances 0.000 description 2
229910000085 borane Inorganic materials 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
238000005251 capillar electrophoresis Methods 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
210000000845 cartilage Anatomy 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
229940125782 compound 2 Drugs 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000000502 dialysis Methods 0.000 description 2
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003792 electrolyte Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000012149 elution buffer Substances 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
238000006911 enzymatic reaction Methods 0.000 description 2
238000000105 evaporative light scattering detection Methods 0.000 description 2
229940012444 factor xiii Drugs 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
235000011087 fumaric acid Nutrition 0.000 description 2
230000006870 function Effects 0.000 description 2
FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000003862 glucocorticoid Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
229930195712 glutamate Natural products 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
125000004474 heteroalkylene group Chemical group 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
239000005556 hormone Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
235000003642 hunger Nutrition 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
230000002163 immunogen Effects 0.000 description 2
208000014674 injury Diseases 0.000 description 2
230000003993 interaction Effects 0.000 description 2
125000003965 isoxazolidinyl group Chemical group 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
208000019423 liver disease Diseases 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
230000005012 migration Effects 0.000 description 2
238000013508 migration Methods 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 2
IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
239000008188 pellet Substances 0.000 description 2
238000012510 peptide mapping method Methods 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
229920002401 polyacrylamide Polymers 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229960004063 propylene glycol Drugs 0.000 description 2
235000013772 propylene glycol Nutrition 0.000 description 2
230000009145 protein modification Effects 0.000 description 2
239000012264 purified product Substances 0.000 description 2
150000003222 pyridines Chemical class 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000011160 research Methods 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
210000000614 rib Anatomy 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007921 spray Substances 0.000 description 2
230000037351 starvation Effects 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
239000000725 suspension Substances 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
210000002303 tibia Anatomy 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000001425 triazolyl group Chemical group 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
238000000825 ultraviolet detection Methods 0.000 description 2
239000004474 valine Substances 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 1
VEVRNHHLCPGNDU-MUGJNUQGSA-N (2s)-2-amino-5-[1-[(5s)-5-amino-5-carboxypentyl]-3,5-bis[(3s)-3-amino-3-carboxypropyl]pyridin-1-ium-4-yl]pentanoate Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(CC[C@H](N)C(O)=O)=C(CCC[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 VEVRNHHLCPGNDU-MUGJNUQGSA-N 0.000 description 1
JIMLDJNLXLMGLX-JTQLQIEISA-N (2s)-5-amino-5-oxo-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 JIMLDJNLXLMGLX-JTQLQIEISA-N 0.000 description 1
125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
MXOAEAUPQDYUQM-QMMMGPOBSA-N (S)-chlorphenesin Chemical compound OC[C@H](O)COC1=CC=C(Cl)C=C1 MXOAEAUPQDYUQM-QMMMGPOBSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
LLUJWSJRGKQEMM-UHFFFAOYSA-N 1,3-diaminooxypropan-2-ol Chemical compound NOCC(O)CON LLUJWSJRGKQEMM-UHFFFAOYSA-N 0.000 description 1
MRHPRDYMSACWSG-UHFFFAOYSA-N 1,3-diaminopropan-1-ol Chemical compound NCCC(N)O MRHPRDYMSACWSG-UHFFFAOYSA-N 0.000 description 1
YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 description 1
HZQDOCURSMJHFJ-UHFFFAOYSA-N 1-[3-(2-aminoethoxy)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(OCCN)=C1 HZQDOCURSMJHFJ-UHFFFAOYSA-N 0.000 description 1
ZFCOWLYQBLYESO-UHFFFAOYSA-N 1-[4-(2-aminoethoxy)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(OCCN)C=C1 ZFCOWLYQBLYESO-UHFFFAOYSA-N 0.000 description 1
GHEAOCPXAWGVSO-UHFFFAOYSA-N 1-[4-(2-aminoethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(CCN)C=C1 GHEAOCPXAWGVSO-UHFFFAOYSA-N 0.000 description 1
SVUFTNBKCAMKND-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]ethanone Chemical group CC(=O)C1=CC=C(CN)C=C1 SVUFTNBKCAMKND-UHFFFAOYSA-N 0.000 description 1
JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
XABCFXXGZPWJQP-UHFFFAOYSA-N 3-aminoadipic acid Chemical compound OC(=O)CC(N)CCC(O)=O XABCFXXGZPWJQP-UHFFFAOYSA-N 0.000 description 1
PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
208000004611 Abdominal Obesity Diseases 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
208000010392 Bone Fractures Diseases 0.000 description 1
LVDKZNITIUWNER-UHFFFAOYSA-N Bronopol Chemical compound OCC(Br)(CO)[N+]([O-])=O LVDKZNITIUWNER-UHFFFAOYSA-N 0.000 description 1
239000012619 Butyl Sepharose® Substances 0.000 description 1
QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 1
PJZBXYKLDPBGFD-UHFFFAOYSA-N CNC(C(CO)N)=O Chemical compound CNC(C(CO)N)=O PJZBXYKLDPBGFD-UHFFFAOYSA-N 0.000 description 1
GUZHNHLBMZROSU-UHFFFAOYSA-N CNC(CC=O)=O Chemical compound CNC(CC=O)=O GUZHNHLBMZROSU-UHFFFAOYSA-N 0.000 description 1
206010006895 Cachexia Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
101000666165 Cavia cutleri Protein-glutamine gamma-glutamyltransferase 2 Proteins 0.000 description 1
206010065941 Central obesity Diseases 0.000 description 1
GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
241000548230 Crassostrea angulata Species 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
229930182847 D-glutamic acid Natural products 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
201000010374 Down Syndrome Diseases 0.000 description 1
206010058314 Dysplasia Diseases 0.000 description 1
208000010228 Erectile Dysfunction Diseases 0.000 description 1
241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
208000001362 Fetal Growth Retardation Diseases 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
206010070531 Foetal growth restriction Diseases 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
102000030902 Galactosyltransferase Human genes 0.000 description 1
108060003306 Galactosyltransferase Proteins 0.000 description 1
229920001503 Glucan Polymers 0.000 description 1
102000016901 Glutamate dehydrogenase Human genes 0.000 description 1
108010008488 Glycylglycine Proteins 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000037357 HIV infectious disease Diseases 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
241001622557 Hesperia Species 0.000 description 1
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
229920001612 Hydroxyethyl starch Polymers 0.000 description 1
LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
206010020649 Hyperkeratosis Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
208000003456 Juvenile Arthritis Diseases 0.000 description 1
206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
JUQLUIFNNFIIKC-YFKPBYRVSA-N L-2-aminopimelic acid Chemical compound OC(=O)[C@@H](N)CCCCC(O)=O JUQLUIFNNFIIKC-YFKPBYRVSA-N 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
206010049287 Lipodystrophy acquired Diseases 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
208000007466 Male Infertility Diseases 0.000 description 1
208000002720 Malnutrition Diseases 0.000 description 1
229920002774 Maltodextrin Polymers 0.000 description 1
239000005913 Maltodextrin Substances 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
208000001145 Metabolic Syndrome Diseases 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
208000021642 Muscular disease Diseases 0.000 description 1
201000009623 Myopathy Diseases 0.000 description 1
241000872931 Myoporum sandwicense Species 0.000 description 1
241001467460 Myxogastria Species 0.000 description 1
FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
OLNLSTNFRUFTLM-UHFFFAOYSA-N N-ethylasparagine Chemical compound CCNC(C(O)=O)CC(N)=O OLNLSTNFRUFTLM-UHFFFAOYSA-N 0.000 description 1
YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
108010065338 N-ethylglycine Proteins 0.000 description 1
HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
230000004988 N-glycosylation Effects 0.000 description 1
AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
102000005348 Neuraminidase Human genes 0.000 description 1
108010006232 Neuraminidase Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
206010029748 Noonan syndrome Diseases 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
241001282110 Pagrus major Species 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
101710118538 Protease Proteins 0.000 description 1
239000004373 Pullulan Substances 0.000 description 1
229920001218 Pullulan Polymers 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
239000012614 Q-Sepharose Substances 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
108010077895 Sarcosine Proteins 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
206010049416 Short-bowel syndrome Diseases 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
206010072610 Skeletal dysplasia Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
239000004288 Sodium dehydroacetate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
241000520730 Streptomyces cinnamoneus Species 0.000 description 1
241000499056 Streptomyces griseocarneus Species 0.000 description 1
241000187389 Streptomyces lavendulae Species 0.000 description 1
208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical class [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical class O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical class C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
208000030886 Traumatic Brain injury Diseases 0.000 description 1
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
239000007997 Tricine buffer Substances 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
101710112791 Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
206010052428 Wound Diseases 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
210000000577 adipose tissue Anatomy 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000032683 aging Effects 0.000 description 1
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
108091005588 alkylated proteins Proteins 0.000 description 1
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
238000010640 amide synthesis reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229960002684 aminocaproic acid Drugs 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
210000000617 arm Anatomy 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
210000001188 articular cartilage Anatomy 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
SGUXGJPBTNFBAD-UHFFFAOYSA-L barium iodide Chemical compound [I-].[I-].[Ba+2] SGUXGJPBTNFBAD-UHFFFAOYSA-L 0.000 description 1
229940075444 barium iodide Drugs 0.000 description 1
229910001638 barium iodide Inorganic materials 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
229960001950 benzethonium chloride Drugs 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
239000007998 bicine buffer Substances 0.000 description 1
230000002457 bidirectional effect Effects 0.000 description 1
230000008827 biological function Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
230000006287 biotinylation Effects 0.000 description 1
238000007413 biotinylation Methods 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229960003168 bronopol Drugs 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
210000001217 buttock Anatomy 0.000 description 1
HQABUPZFAYXKJW-UHFFFAOYSA-O butylazanium Chemical compound CCCC[NH3+] HQABUPZFAYXKJW-UHFFFAOYSA-O 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000008004 cell lysis buffer Substances 0.000 description 1
230000019522 cellular metabolic process Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
229960003260 chlorhexidine Drugs 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
229960002242 chlorocresol Drugs 0.000 description 1
MXOAEAUPQDYUQM-UHFFFAOYSA-N chlorphenesin Chemical compound OCC(O)COC1=CC=C(Cl)C=C1 MXOAEAUPQDYUQM-UHFFFAOYSA-N 0.000 description 1
229960003993 chlorphenesin Drugs 0.000 description 1
230000002648 chondrogenic effect Effects 0.000 description 1
208000019069 chronic childhood arthritis Diseases 0.000 description 1
208000020832 chronic kidney disease Diseases 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
230000004087 circulation Effects 0.000 description 1
HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
229940018557 citraconic acid Drugs 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
210000003109 clavicle Anatomy 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000010924 continuous production Methods 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
238000011033 desalting Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
230000029087 digestion Effects 0.000 description 1
KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
230000009144 enzymatic modification Effects 0.000 description 1
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
208000030941 fetal growth restriction Diseases 0.000 description 1
239000012467 final product Substances 0.000 description 1
210000002683 foot Anatomy 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
230000022244 formylation Effects 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
238000007429 general method Methods 0.000 description 1
230000023266 generation of precursor metabolites and energy Effects 0.000 description 1
235000003869 genetically modified organism Nutrition 0.000 description 1
229940063135 genotropin Drugs 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
229940043257 glycylglycine Drugs 0.000 description 1
208000037824 growth disorder Diseases 0.000 description 1
239000003111 growth hormone derivative Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
210000004247 hand Anatomy 0.000 description 1
230000035876 healing Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
150000002373 hemiacetals Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000011540 hip replacement Methods 0.000 description 1
239000003668 hormone analog Substances 0.000 description 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
229940065770 humatrope Drugs 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
229940050526 hydroxyethylstarch Drugs 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000002513 implantation Methods 0.000 description 1
201000001881 impotence Diseases 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
229960000367 inositol Drugs 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
RGXCTRIQQODGIZ-UHFFFAOYSA-O isodesmosine Chemical compound OC(=O)C(N)CCCC[N+]1=CC(CCC(N)C(O)=O)=CC(CCC(N)C(O)=O)=C1CCCC(N)C(O)=O RGXCTRIQQODGIZ-UHFFFAOYSA-O 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
125000000468 ketone group Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000003041 ligament Anatomy 0.000 description 1
230000037356 lipid metabolism Effects 0.000 description 1
208000006132 lipodystrophy Diseases 0.000 description 1
230000004130 lipolysis Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000005976 liver dysfunction Effects 0.000 description 1
208000018773 low birth weight Diseases 0.000 description 1
231100000533 low birth weight Toxicity 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000006166 lysate Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000001071 malnutrition Effects 0.000 description 1
235000000824 malnutrition Nutrition 0.000 description 1
229940035034 maltodextrin Drugs 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
238000013178 mathematical model Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
210000001872 metatarsal bone Anatomy 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
230000035772 mutation Effects 0.000 description 1
LOVVDWAISSOSRE-UHFFFAOYSA-N n-(4-acetylphenyl)-2-aminoacetamide Chemical compound CC(=O)C1=CC=C(NC(=O)CN)C=C1 LOVVDWAISSOSRE-UHFFFAOYSA-N 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
229940063137 norditropin Drugs 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
208000015380 nutritional deficiency disease Diseases 0.000 description 1
229940063149 nutropin Drugs 0.000 description 1
UQVFAWQNJLTMMF-UHFFFAOYSA-N o-(2-aminooxyethyl)hydroxylamine Chemical compound NOCCON UQVFAWQNJLTMMF-UHFFFAOYSA-N 0.000 description 1
COEBNIUQBHSRFT-UHFFFAOYSA-N o-(3-aminooxypropyl)hydroxylamine Chemical compound NOCCCON COEBNIUQBHSRFT-UHFFFAOYSA-N 0.000 description 1
UVTPMAJGFRLLKF-UHFFFAOYSA-N o-(4-aminooxybutyl)hydroxylamine Chemical compound NOCCCCON UVTPMAJGFRLLKF-UHFFFAOYSA-N 0.000 description 1
FDBZGQLBKGNQFT-UHFFFAOYSA-N o-[2-[2-(2-aminooxyethoxy)ethoxy]ethyl]hydroxylamine Chemical compound NOCCOCCOCCON FDBZGQLBKGNQFT-UHFFFAOYSA-N 0.000 description 1
DZEJMPNILLCRBD-UHFFFAOYSA-N o-[2-[2-[2-(2-aminooxyethoxy)ethoxy]ethoxy]ethyl]hydroxylamine Chemical compound NOCCOCCOCCOCCON DZEJMPNILLCRBD-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229940116315 oxalic acid Drugs 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000006320 pegylation Effects 0.000 description 1
230000016446 peptide cross-linking Effects 0.000 description 1
102000033573 peptide hormone binding proteins Human genes 0.000 description 1
108091009595 peptide hormone binding proteins Proteins 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
229960005323 phenoxyethanol Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
229920000166 polytrimethylene carbonate Polymers 0.000 description 1
230000004481 post-translational protein modification Effects 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000012545 processing Methods 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
235000019419 proteases Nutrition 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
235000019423 pullulan Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
238000011002 quantification Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
150000003254 radicals Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000002824 redox indicator Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008439 repair process Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound 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 1
230000007017 scission Effects 0.000 description 1
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
229940117012 serostim Drugs 0.000 description 1
210000002832 shoulder Anatomy 0.000 description 1
SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
210000002356 skeleton Anatomy 0.000 description 1
210000003625 skull Anatomy 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019259 sodium dehydroacetate Nutrition 0.000 description 1
229940079839 sodium dehydroacetate Drugs 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
108700031632 somatrem Proteins 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
125000000185 sucrose group Chemical group 0.000 description 1
XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
235000010269 sulphur dioxide Nutrition 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
210000002435 tendon Anatomy 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
YSMODUONRAFBET-WHFBIAKZSA-N threo-5-hydroxy-L-lysine Chemical compound NC[C@@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-WHFBIAKZSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 description 1
238000001890 transfection Methods 0.000 description 1
230000014616 translation Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
230000009529 traumatic brain injury Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
238000009966 trimming Methods 0.000 description 1
229950002929 trinitrophenol Drugs 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
210000000623 ulna Anatomy 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
239000003643 water by type Substances 0.000 description 1
210000000707 wrist Anatomy 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
AFVLVVWMAFSXCK-UHFFFAOYSA-N α-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(C#N)=CC1=CC=C(O)C=C1 AFVLVVWMAFSXCK-UHFFFAOYSA-N 0.000 description 1