CN1684705A

CN1684705A - 使用具有preptin功能的化合物的方法

使用具有preptin功能的化合物的方法 Download PDF

Info

Publication number: CN1684705A
Authority: CN; China
Prior art keywords: preptin; seq; asp; agonist; cell
Prior art date: 2002-08-01
Legal status : Pending

Application number

CNA03823520XA

Other languages

English (en)

Chinese (zh)

Inventor

G·J·S·库珀

C·M·比沙南

G·C·詹姆斯

Current Assignee

Protemix Corp Ltd

Original Assignee

PUROTMIX Ltd

Priority date

2002-08-01

Filing date

2003-08-01

Publication date

2005-10-19

2003-08-01 Application filed by PUROTMIX Ltd filed Critical PUROTMIX Ltd

2005-10-19 Publication of CN1684705A publication Critical patent/CN1684705A/zh

Status Pending legal-status Critical Current

Links

102100025947 Insulin-like growth factor II Human genes 0.000 title claims abstract description 339
101800001717 Preptin Proteins 0.000 title claims abstract description 338
238000000034 method Methods 0.000 title claims abstract description 154
150000001875 compounds Chemical class 0.000 title claims abstract description 65
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims abstract description 115
239000000556 agonist Substances 0.000 claims abstract description 92
150000003839 salts Chemical class 0.000 claims abstract description 58
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 50
201000010099 disease Diseases 0.000 claims abstract description 36
208000027418 Wounds and injury Diseases 0.000 claims abstract description 25
208000035475 disorder Diseases 0.000 claims abstract description 12
210000004027 cell Anatomy 0.000 claims description 128
108090000765 processed proteins & peptides Proteins 0.000 claims description 95
241001597008 Nomeidae Species 0.000 claims description 39
208000024891 symptom Diseases 0.000 claims description 31
238000011282 treatment Methods 0.000 claims description 29
206010052428 Wound Diseases 0.000 claims description 24
239000012190 activator Substances 0.000 claims description 22
239000012634 fragment Substances 0.000 claims description 22
239000000203 mixture Substances 0.000 claims description 22
238000002360 preparation method Methods 0.000 claims description 21
DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical class CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims description 17
230000006378 damage Effects 0.000 claims description 16
230000009467 reduction Effects 0.000 claims description 15
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 13
239000000758 substrate Substances 0.000 claims description 12
230000004663 cell proliferation Effects 0.000 claims description 11
230000003915 cell function Effects 0.000 claims description 9
125000000539 amino acid group Chemical group 0.000 claims description 8
230000037396 body weight Effects 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
210000002950 fibroblast Anatomy 0.000 claims description 8
230000003914 insulin secretion Effects 0.000 claims description 8
230000035755 proliferation Effects 0.000 claims description 8
210000001519 tissue Anatomy 0.000 claims description 8
101500026260 Rattus norvegicus Preptin Proteins 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
230000006872 improvement Effects 0.000 claims description 7
210000004877 mucosa Anatomy 0.000 claims description 7
230000001225 therapeutic effect Effects 0.000 claims description 7
239000006071 cream Substances 0.000 claims description 6
230000012010 growth Effects 0.000 claims description 6
201000001421 hyperglycemia Diseases 0.000 claims description 6
239000005022 packaging material Substances 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
238000002054 transplantation Methods 0.000 claims description 6
241000699666 Mus <mouse, genus> Species 0.000 claims description 5
241000699670 Mus sp. Species 0.000 claims description 5
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
230000001154 acute effect Effects 0.000 claims description 5
230000024245 cell differentiation Effects 0.000 claims description 5
230000006727 cell loss Effects 0.000 claims description 5
210000002808 connective tissue Anatomy 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
230000001815 facial effect Effects 0.000 claims description 5
230000036737 immune function Effects 0.000 claims description 5
210000000214 mouth Anatomy 0.000 claims description 5
210000003205 muscle Anatomy 0.000 claims description 5
239000002674 ointment Substances 0.000 claims description 5
230000008929 regeneration Effects 0.000 claims description 5
238000011069 regeneration method Methods 0.000 claims description 5
208000025865 Ulcer Diseases 0.000 claims description 4
238000005336 cracking Methods 0.000 claims description 4
210000001035 gastrointestinal tract Anatomy 0.000 claims description 4
231100000397 ulcer Toxicity 0.000 claims description 4
208000031229 Cardiomyopathies Diseases 0.000 claims description 3
206010040943 Skin Ulcer Diseases 0.000 claims description 3
210000000981 epithelium Anatomy 0.000 claims description 3
230000001965 increasing effect Effects 0.000 claims description 3
230000002829 reductive effect Effects 0.000 claims description 3
231100000019 skin ulcer Toxicity 0.000 claims description 3
230000000472 traumatic effect Effects 0.000 claims description 3
230000029663 wound healing Effects 0.000 claims description 3
208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
208000024827 Alzheimer disease Diseases 0.000 claims description 2
208000009043 Chemical Burns Diseases 0.000 claims description 2
208000018380 Chemical injury Diseases 0.000 claims description 2
206010009900 Colitis ulcerative Diseases 0.000 claims description 2
208000028006 Corneal injury Diseases 0.000 claims description 2
208000011231 Crohn disease Diseases 0.000 claims description 2
206010011985 Decubitus ulcer Diseases 0.000 claims description 2
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
206010056340 Diabetic ulcer Diseases 0.000 claims description 2
208000032843 Hemorrhage Diseases 0.000 claims description 2
206010022489 Insulin Resistance Diseases 0.000 claims description 2
208000009525 Myocarditis Diseases 0.000 claims description 2
206010033799 Paralysis Diseases 0.000 claims description 2
208000018737 Parkinson disease Diseases 0.000 claims description 2
208000004210 Pressure Ulcer Diseases 0.000 claims description 2
208000033626 Renal failure acute Diseases 0.000 claims description 2
206010053615 Thermal burn Diseases 0.000 claims description 2
201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
238000002512 chemotherapy Methods 0.000 claims description 2
238000005538 encapsulation Methods 0.000 claims description 2
208000019622 heart disease Diseases 0.000 claims description 2
230000001771 impaired effect Effects 0.000 claims description 2
208000014674 injury Diseases 0.000 claims description 2
208000028867 ischemia Diseases 0.000 claims description 2
201000010901 lateral sclerosis Diseases 0.000 claims description 2
230000033001 locomotion Effects 0.000 claims description 2
230000001404 mediated effect Effects 0.000 claims description 2
210000002161 motor neuron Anatomy 0.000 claims description 2
208000005264 motor neuron disease Diseases 0.000 claims description 2
201000006938 muscular dystrophy Diseases 0.000 claims description 2
230000010016 myocardial function Effects 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
230000016273 neuron death Effects 0.000 claims description 2
210000001428 peripheral nervous system Anatomy 0.000 claims description 2
210000000278 spinal cord Anatomy 0.000 claims description 2
230000008467 tissue growth Effects 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
125000003275 alpha amino acid group Chemical group 0.000 claims 34
QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 claims 13
IPTUBUUIFRZMJK-ACRUOGEOSA-N Lys-Phe-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 IPTUBUUIFRZMJK-ACRUOGEOSA-N 0.000 claims 12
OYEUSRAZOGIDBY-JYJNAYRXSA-N Pro-Arg-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OYEUSRAZOGIDBY-JYJNAYRXSA-N 0.000 claims 12
FUOGXAQMNJMBFG-WPRPVWTQSA-N Pro-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FUOGXAQMNJMBFG-WPRPVWTQSA-N 0.000 claims 12
108010015792 glycyllysine Proteins 0.000 claims 12
108010089198 phenylalanyl-prolyl-arginine Proteins 0.000 claims 12
ZHQWPWQNVRCXAX-XQQFMLRXSA-N Val-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZHQWPWQNVRCXAX-XQQFMLRXSA-N 0.000 claims 11
SVFOIXMRMLROHO-SRVKXCTJSA-N Asp-Asp-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SVFOIXMRMLROHO-SRVKXCTJSA-N 0.000 claims 10
KUBFPYIMAGXGBT-ACZMJKKPSA-N Gln-Ser-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KUBFPYIMAGXGBT-ACZMJKKPSA-N 0.000 claims 10
OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 claims 10
ZOCJFNXUVSGBQI-HSHDSVGOSA-N Thr-Trp-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O ZOCJFNXUVSGBQI-HSHDSVGOSA-N 0.000 claims 10
DOBIBIXIHJKVJF-XKBZYTNZSA-N Thr-Ser-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O DOBIBIXIHJKVJF-XKBZYTNZSA-N 0.000 claims 9
108010020532 tyrosyl-proline Proteins 0.000 claims 9
108010047495 alanylglycine Proteins 0.000 claims 8
OACQOWPRWGNKTP-AVGNSLFASA-N Gln-Tyr-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O OACQOWPRWGNKTP-AVGNSLFASA-N 0.000 claims 7
FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 claims 5
TWPCWKVOZDUYAA-KKUMJFAQSA-N Lys-Phe-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O TWPCWKVOZDUYAA-KKUMJFAQSA-N 0.000 claims 5
CJZTUKSFZUSNCC-FXQIFTODSA-N Pro-Asp-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 CJZTUKSFZUSNCC-FXQIFTODSA-N 0.000 claims 4
MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 claims 4
BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 claims 4
108010057821 leucylproline Proteins 0.000 claims 4
NTUPOKHATNSWCY-PMPSAXMXSA-N (2s)-2-[[(2s)-1-[(2r)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=CC=C1 NTUPOKHATNSWCY-PMPSAXMXSA-N 0.000 claims 3
KCOPOPKJRHVGPE-AQZXSJQPSA-N Asp-Thr-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O KCOPOPKJRHVGPE-AQZXSJQPSA-N 0.000 claims 3
MHZXESQPPXOING-KBPBESRZSA-N Gly-Lys-Phe Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MHZXESQPPXOING-KBPBESRZSA-N 0.000 claims 3
NNCDAORZCMPZPX-GUBZILKMSA-N Lys-Gln-Ser Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N NNCDAORZCMPZPX-GUBZILKMSA-N 0.000 claims 3
101500026263 Mus musculus Preptin Proteins 0.000 claims 3
ABQFNJAFONNUTH-FHWLQOOXSA-N Phe-Gln-Tyr Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N ABQFNJAFONNUTH-FHWLQOOXSA-N 0.000 claims 3
QILPDQCTQZDHFM-HJGDQZAQSA-N Thr-Gln-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QILPDQCTQZDHFM-HJGDQZAQSA-N 0.000 claims 3
RGYCVIZZTUBSSG-JYJNAYRXSA-N Tyr-Pro-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O RGYCVIZZTUBSSG-JYJNAYRXSA-N 0.000 claims 3
108010073025 phenylalanylphenylalanine Proteins 0.000 claims 3
PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 claims 2
BYKZWDGMJLNFJY-XKBZYTNZSA-N Gln-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)O BYKZWDGMJLNFJY-XKBZYTNZSA-N 0.000 claims 2
PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 claims 2
MYNYCUXMIIWUNW-IEGACIPQSA-N Thr-Trp-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MYNYCUXMIIWUNW-IEGACIPQSA-N 0.000 claims 2
UJMCYJKPDFQLHX-XGEHTFHBSA-N Val-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N)O UJMCYJKPDFQLHX-XGEHTFHBSA-N 0.000 claims 2
108010008355 arginyl-glutamine Proteins 0.000 claims 2
HOQGTAIGQSDCHR-SRVKXCTJSA-N Asp-Asn-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HOQGTAIGQSDCHR-SRVKXCTJSA-N 0.000 claims 1
206010008190 Cerebrovascular accident Diseases 0.000 claims 1
206010061245 Internal injury Diseases 0.000 claims 1
206010056969 Necrobiosis lipoidica diabeticorum Diseases 0.000 claims 1
RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 claims 1
CRZRTKAVUUGKEQ-ACZMJKKPSA-N Ser-Gln-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CRZRTKAVUUGKEQ-ACZMJKKPSA-N 0.000 claims 1
208000006011 Stroke Diseases 0.000 claims 1
230000001066 destructive effect Effects 0.000 claims 1
230000003526 lymphopoietic effect Effects 0.000 claims 1
201000008043 necrobiosis lipoidica Diseases 0.000 claims 1
230000003820 β-cell dysfunction Effects 0.000 claims 1
-1 preptins Chemical class 0.000 abstract description 9
241000282412 Homo Species 0.000 abstract description 2
230000003247 decreasing effect Effects 0.000 abstract 3
108090000623 proteins and genes Proteins 0.000 description 116
150000001413 amino acids Chemical class 0.000 description 63
102000004169 proteins and genes Human genes 0.000 description 63
235000018102 proteins Nutrition 0.000 description 58
229940024606 amino acid Drugs 0.000 description 54
235000001014 amino acid Nutrition 0.000 description 52
108020004414 DNA Proteins 0.000 description 51
230000014509 gene expression Effects 0.000 description 41
102000004196 processed proteins & peptides Human genes 0.000 description 38
150000007523 nucleic acids Chemical class 0.000 description 33
230000006870 function Effects 0.000 description 32
102000039446 nucleic acids Human genes 0.000 description 31
108020004707 nucleic acids Proteins 0.000 description 31
229920001184 polypeptide Polymers 0.000 description 31
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 30
238000001415 gene therapy Methods 0.000 description 27
239000002773 nucleotide Substances 0.000 description 22
125000003729 nucleotide group Chemical group 0.000 description 22
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 20
239000002253 acid Substances 0.000 description 20
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 18
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 18
239000000463 material Substances 0.000 description 18
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 17
230000008859 change Effects 0.000 description 17
239000013612 plasmid Substances 0.000 description 17
108090001061 Insulin Proteins 0.000 description 16
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 16
206010012601 diabetes mellitus Diseases 0.000 description 16
102000004877 Insulin Human genes 0.000 description 15
230000001580 bacterial effect Effects 0.000 description 15
238000009396 hybridization Methods 0.000 description 15
229940125396 insulin Drugs 0.000 description 15
241000588724 Escherichia coli Species 0.000 description 13
238000005516 engineering process Methods 0.000 description 13
102000040430 polynucleotide Human genes 0.000 description 13
108091033319 polynucleotide Proteins 0.000 description 13
239000002157 polynucleotide Substances 0.000 description 13
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 12
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 12
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 12
108091034117 Oligonucleotide Proteins 0.000 description 12
239000008194 pharmaceutical composition Substances 0.000 description 12
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 11
229910052799 carbon Inorganic materials 0.000 description 11
230000000694 effects Effects 0.000 description 11
238000003259 recombinant expression Methods 0.000 description 11
230000010076 replication Effects 0.000 description 11
230000028327 secretion Effects 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
241000700605 Viruses Species 0.000 description 10
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 9
241000894006 Bacteria Species 0.000 description 9
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
108091028043 Nucleic acid sequence Proteins 0.000 description 9
239000000047 product Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 8
108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 8
240000004808 Saccharomyces cerevisiae Species 0.000 description 8
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 8
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
239000013604 expression vector Substances 0.000 description 8
108020004999 messenger RNA Proteins 0.000 description 8
238000002703 mutagenesis Methods 0.000 description 8
231100000350 mutagenesis Toxicity 0.000 description 8
229920001223 polyethylene glycol Polymers 0.000 description 8
239000013603 viral vector Substances 0.000 description 8
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 7
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 7
206010028980 Neoplasm Diseases 0.000 description 7
108010034634 Repressor Proteins Proteins 0.000 description 7
102000009661 Repressor Proteins Human genes 0.000 description 7
239000002299 complementary DNA Substances 0.000 description 7
239000003623 enhancer Substances 0.000 description 7
239000008103 glucose Substances 0.000 description 7
210000004962 mammalian cell Anatomy 0.000 description 7
239000003921 oil Substances 0.000 description 7
210000000496 pancreas Anatomy 0.000 description 7
230000001105 regulatory effect Effects 0.000 description 7
239000000523 sample Substances 0.000 description 7
229940104230 thymidine Drugs 0.000 description 7
239000013598 vector Substances 0.000 description 7
239000004475 Arginine Substances 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
108700039691 Genetic Promoter Regions Proteins 0.000 description 6
241000238631 Hexapoda Species 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000012217 deletion Methods 0.000 description 6
230000037430 deletion Effects 0.000 description 6
230000008676 import Effects 0.000 description 6
230000001939 inductive effect Effects 0.000 description 6
238000010369 molecular cloning Methods 0.000 description 6
239000002243 precursor Substances 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
239000000243 solution Substances 0.000 description 6
241000701161 unidentified adenovirus Species 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
239000004471 Glycine Substances 0.000 description 5
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 5
239000000969 carrier Substances 0.000 description 5
230000010261 cell growth Effects 0.000 description 5
238000010367 cloning Methods 0.000 description 5
239000002270 dispersing agent Substances 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
230000002068 genetic effect Effects 0.000 description 5
229960002989 glutamic acid Drugs 0.000 description 5
210000004153 islets of langerhan Anatomy 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000003550 marker Substances 0.000 description 5
230000004044 response Effects 0.000 description 5
239000007790 solid phase Substances 0.000 description 5
239000000375 suspending agent Substances 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
230000003612 virological effect Effects 0.000 description 5
229920000858 Cyclodextrin Polymers 0.000 description 4
241000701022 Cytomegalovirus Species 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
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
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 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
108020005187 Oligonucleotide Probes Proteins 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000013459 approach Methods 0.000 description 4
210000000481 breast Anatomy 0.000 description 4
201000011510 cancer Diseases 0.000 description 4
238000010276 construction Methods 0.000 description 4
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
235000018417 cysteine Nutrition 0.000 description 4
230000008034 disappearance Effects 0.000 description 4
239000003995 emulsifying agent Substances 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
239000002751 oligonucleotide probe Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
238000012545 processing Methods 0.000 description 4
238000000746 purification Methods 0.000 description 4
238000012216 screening Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
239000013589 supplement Substances 0.000 description 4
238000013518 transcription Methods 0.000 description 4
230000035897 transcription Effects 0.000 description 4
238000001890 transfection Methods 0.000 description 4
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
239000004474 valine Substances 0.000 description 4
DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 3
DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
108020004705 Codon Proteins 0.000 description 3
241000702421 Dependoparvovirus Species 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
206010027336 Menstruation delayed Diseases 0.000 description 3
102000003792 Metallothionein Human genes 0.000 description 3
108090000157 Metallothionein Proteins 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
108091034057 RNA (poly(A)) Proteins 0.000 description 3
239000012980 RPMI-1640 medium Substances 0.000 description 3
208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 3
206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 3
102000006601 Thymidine Kinase Human genes 0.000 description 3
108020004440 Thymidine kinase Proteins 0.000 description 3
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 3
235000004279 alanine Nutrition 0.000 description 3
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
229960000723 ampicillin Drugs 0.000 description 3
230000000692 anti-sense effect Effects 0.000 description 3
235000003704 aspartic acid Nutrition 0.000 description 3
230000008901 benefit Effects 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
230000033228 biological regulation Effects 0.000 description 3
210000004899 c-terminal region Anatomy 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
230000022131 cell cycle Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
210000004748 cultured cell Anatomy 0.000 description 3
230000002950 deficient Effects 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
235000013601 eggs Nutrition 0.000 description 3
238000011156 evaluation Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
235000013922 glutamic acid Nutrition 0.000 description 3
239000004220 glutamic acid Substances 0.000 description 3
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
230000001976 improved effect Effects 0.000 description 3
230000006698 induction Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
230000003834 intracellular effect Effects 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
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 3
208000030159 metabolic disease Diseases 0.000 description 3
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
229930182817 methionine Natural products 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
230000008520 organization Effects 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000002574 poison Substances 0.000 description 3
231100000614 poison Toxicity 0.000 description 3
230000008569 process Effects 0.000 description 3
230000001737 promoting effect Effects 0.000 description 3
238000010188 recombinant method Methods 0.000 description 3
230000006798 recombination Effects 0.000 description 3
238000005215 recombination Methods 0.000 description 3
230000001177 retroviral effect Effects 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
230000014616 translation Effects 0.000 description 3
229910052722 tritium Inorganic materials 0.000 description 3
241001430294 unidentified retrovirus Species 0.000 description 3
238000005406 washing Methods 0.000 description 3
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 2
102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
241001155433 Centrarchus macropterus Species 0.000 description 2
244000131522 Citrus pyriformis Species 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
241000206602 Eukaryota Species 0.000 description 2
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 2
101800000224 Glucagon-like peptide 1 Proteins 0.000 description 2
102400000322 Glucagon-like peptide 1 Human genes 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
102000018997 Growth Hormone Human genes 0.000 description 2
108010051696 Growth Hormone Proteins 0.000 description 2
102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
108091027305 Heteroduplex Proteins 0.000 description 2
108010033040 Histones Proteins 0.000 description 2
102000002265 Human Growth Hormone Human genes 0.000 description 2
108010000521 Human Growth Hormone Proteins 0.000 description 2
239000000854 Human Growth Hormone Substances 0.000 description 2
241000725303 Human immunodeficiency virus Species 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
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
108091027981 Response element Proteins 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
101710137500 T7 RNA polymerase Proteins 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
238000007605 air drying Methods 0.000 description 2
230000003321 amplification Effects 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
238000010171 animal model Methods 0.000 description 2
101150042295 arfA gene Proteins 0.000 description 2
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
229920001222 biopolymer Polymers 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
102220369446 c.1274G>A Human genes 0.000 description 2
229960000846 camphor Drugs 0.000 description 2
229940025250 camphora Drugs 0.000 description 2
239000010238 camphora Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000000845 cartilage Anatomy 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
238000007385 chemical modification Methods 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000005482 chemotactic factor Substances 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
230000002759 chromosomal effect Effects 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000012531 culture fluid Substances 0.000 description 2
XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
229960003067 cystine Drugs 0.000 description 2
230000007423 decrease Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
230000004069 differentiation Effects 0.000 description 2
LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
230000000763 evoking effect Effects 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
210000003754 fetus Anatomy 0.000 description 2
230000003328 fibroblastic effect Effects 0.000 description 2
230000004927 fusion Effects 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
238000012239 gene modification Methods 0.000 description 2
230000005017 genetic modification Effects 0.000 description 2
235000013617 genetically modified food Nutrition 0.000 description 2
210000004907 gland Anatomy 0.000 description 2
102000035122 glycosylated proteins Human genes 0.000 description 2
108091005608 glycosylated proteins Proteins 0.000 description 2
230000013595 glycosylation Effects 0.000 description 2
238000006206 glycosylation reaction Methods 0.000 description 2
239000000122 growth hormone Substances 0.000 description 2
230000036541 health Effects 0.000 description 2
229910001385 heavy metal Inorganic materials 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
235000003642 hunger Nutrition 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
150000001261 hydroxy acids Chemical group 0.000 description 2
230000028993 immune response Effects 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000000977 initiatory effect Effects 0.000 description 2
239000012212 insulator Substances 0.000 description 2
238000001361 intraarterial administration Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229920000831 ionic polymer Polymers 0.000 description 2
XUWPJKDMEZSVTP-LTYMHZPRSA-N kalafungina Chemical compound O=C1C2=C(O)C=CC=C2C(=O)C2=C1[C@@H](C)O[C@H]1[C@@H]2OC(=O)C1 XUWPJKDMEZSVTP-LTYMHZPRSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000010534 mechanism of action Effects 0.000 description 2
235000001968 nicotinic acid Nutrition 0.000 description 2
239000011664 nicotinic acid Substances 0.000 description 2
239000000346 nonvolatile oil Substances 0.000 description 2
238000003199 nucleic acid amplification method Methods 0.000 description 2
101150087557 omcB gene Proteins 0.000 description 2
101150115693 ompA gene Proteins 0.000 description 2
108010032737 oxalyl CoA decarboxylase Proteins 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
230000010412 perfusion Effects 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
239000008363 phosphate buffer Substances 0.000 description 2
239000013600 plasmid vector Substances 0.000 description 2
238000006116 polymerization reaction Methods 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000008439 repair process Effects 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
108091008146 restriction endonucleases Proteins 0.000 description 2
238000010839 reverse transcription Methods 0.000 description 2
210000003705 ribosome Anatomy 0.000 description 2
230000000630 rising effect Effects 0.000 description 2
238000005070 sampling Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
235000010199 sorbic acid Nutrition 0.000 description 2
239000004334 sorbic acid Substances 0.000 description 2
229940075582 sorbic acid Drugs 0.000 description 2
241000894007 species Species 0.000 description 2
230000037351 starvation Effects 0.000 description 2
229960002385 streptomycin sulfate Drugs 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
108700004027 tat Genes Proteins 0.000 description 2
101150098170 tat gene Proteins 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000002103 transcriptional effect Effects 0.000 description 2
238000013519 translation Methods 0.000 description 2
SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 2
229960002109 tuberculosis vaccine Drugs 0.000 description 2
RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 2
210000004885 white matter Anatomy 0.000 description 2
CJDRUOGAGYHKKD-XMTJACRCSA-N (+)-Ajmaline Natural products O[C@H]1[C@@H](CC)[C@@H]2[C@@H]3[C@H](O)[C@@]45[C@@H](N(C)c6c4cccc6)[C@@H](N1[C@H]3C5)C2 CJDRUOGAGYHKKD-XMTJACRCSA-N 0.000 description 1
NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 1
GWSURTDMLUFMJH-FOCLMDBBSA-N (e)-hexadec-1-en-1-ol Chemical compound CCCCCCCCCCCCCC\C=C\O GWSURTDMLUFMJH-FOCLMDBBSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
IQXJCCZJOIKIAD-UHFFFAOYSA-N 1-(2-methoxyethoxy)hexadecane Chemical compound CCCCCCCCCCCCCCCCOCCOC IQXJCCZJOIKIAD-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 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
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 1
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
102000007469 Actins Human genes 0.000 description 1
108010085238 Actins Proteins 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
244000105975 Antidesma platyphyllum Species 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
241000713826 Avian leukosis virus Species 0.000 description 1
210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
101100348617 Candida albicans (strain SC5314 / ATCC MYA-2876) NIK1 gene Proteins 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
102000019034 Chemokines Human genes 0.000 description 1
108010012236 Chemokines Proteins 0.000 description 1
108020004998 Chloroplast DNA Proteins 0.000 description 1
102100031065 Choline kinase alpha Human genes 0.000 description 1
241000251730 Chondrichthyes Species 0.000 description 1
108091062157 Cis-regulatory element Proteins 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
235000005979 Citrus limon Nutrition 0.000 description 1
108091033380 Coding strand Proteins 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
244000205754 Colocasia esculenta Species 0.000 description 1
235000006481 Colocasia esculenta Nutrition 0.000 description 1
108020004635 Complementary DNA Proteins 0.000 description 1
102000012410 DNA Ligases Human genes 0.000 description 1
108010061982 DNA Ligases Proteins 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
108010076804 DNA Restriction Enzymes Proteins 0.000 description 1
230000008836 DNA modification Effects 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000032781 Diabetic cardiomyopathy Diseases 0.000 description 1
102100024746 Dihydrofolate reductase Human genes 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
108090000204 Dipeptidase 1 Proteins 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
102000002322 Egg Proteins Human genes 0.000 description 1
108010000912 Egg Proteins Proteins 0.000 description 1
241000792859 Enema Species 0.000 description 1
241001524679 Escherichia virus M13 Species 0.000 description 1
108700039887 Essential Genes Proteins 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
241000700662 Fowlpox virus Species 0.000 description 1
101710086299 Fructose-2,6-bisphosphatase Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108700007698 Genetic Terminator Regions Proteins 0.000 description 1
229920001503 Glucan Polymers 0.000 description 1
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
241000175212 Herpesvirales Species 0.000 description 1
101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
102000008100 Human Serum Albumin Human genes 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
241000701024 Human betaherpesvirus 5 Species 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
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
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
241000235058 Komagataella pastoris Species 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
QWCKQJZIFLGMSD-VKHMYHEASA-N L-alpha-aminobutyric acid Chemical compound CC[C@H](N)C(O)=O QWCKQJZIFLGMSD-VKHMYHEASA-N 0.000 description 1
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
150000008575 L-amino acids Chemical group 0.000 description 1
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
208000008771 Lymphadenopathy Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
229920003091 Methocel™ Polymers 0.000 description 1
108020005196 Mitochondrial DNA Proteins 0.000 description 1
241000713869 Moloney murine leukemia virus Species 0.000 description 1
241000713333 Mouse mammary tumor virus Species 0.000 description 1
241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
108091061960 Naked DNA Proteins 0.000 description 1
206010059605 Necrobiosis Diseases 0.000 description 1
208000015906 Necrobiotic disease Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
241000256259 Noctuidae Species 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
101710163270 Nuclease Proteins 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
108091081548 Palindromic sequence Proteins 0.000 description 1
108700020797 Parathyroid Hormone-Related Proteins 0.000 description 1
102000043299 Parathyroid hormone-related Human genes 0.000 description 1
241001494479 Pecora Species 0.000 description 1
229920002230 Pectic acid Polymers 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
241000235648 Pichia Species 0.000 description 1
102100024588 Podocalyxin-like protein 2 Human genes 0.000 description 1
108091010857 Podocalyxin-like protein 2 Proteins 0.000 description 1
101710182846 Polyhedrin Proteins 0.000 description 1
241001505332 Polyomavirus sp. Species 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
241000125945 Protoparvovirus Species 0.000 description 1
108091008109 Pseudogenes Proteins 0.000 description 1
102000057361 Pseudogenes Human genes 0.000 description 1
101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
241000714474 Rous sarcoma virus Species 0.000 description 1
101100007329 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS1 gene Proteins 0.000 description 1
241000701062 Saimiriine gammaherpesvirus 2 Species 0.000 description 1
241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
108091058545 Secretory proteins Proteins 0.000 description 1
102000040739 Secretory proteins Human genes 0.000 description 1
102000003800 Selectins Human genes 0.000 description 1
108090000184 Selectins Proteins 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
241000713896 Spleen necrosis virus Species 0.000 description 1
241000256248 Spodoptera Species 0.000 description 1
241001655322 Streptomycetales Species 0.000 description 1
241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
241000218636 Thuja Species 0.000 description 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
241001672648 Vieira Species 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
206010048031 Wound dehiscence Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
208000013228 adenopathy Diseases 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
235000008206 alpha-amino acids Nutrition 0.000 description 1
HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
229940043377 alpha-cyclodextrin Drugs 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229960002684 aminocaproic acid Drugs 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
239000001166 ammonium sulphate Substances 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
239000012491 analyte Substances 0.000 description 1
230000031016 anaphase Effects 0.000 description 1
229940031955 anhydrous lanolin Drugs 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
239000000074 antisense oligonucleotide Substances 0.000 description 1
238000012230 antisense oligonucleotides Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
150000001576 beta-amino acids Chemical class 0.000 description 1
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
102000006635 beta-lactamase Human genes 0.000 description 1
229960004853 betadex Drugs 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000008827 biological function Effects 0.000 description 1
210000003995 blood forming stem cell Anatomy 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
150000007516 brønsted-lowry acids Chemical class 0.000 description 1
150000007528 brønsted-lowry bases Chemical class 0.000 description 1
239000012928 buffer substance Substances 0.000 description 1
238000010804 cDNA synthesis Methods 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
230000011712 cell development Effects 0.000 description 1
230000010307 cell transformation Effects 0.000 description 1
210000004671 cell-free system Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229940106189 ceramide Drugs 0.000 description 1
ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
229950009789 cetomacrogol 1000 Drugs 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
239000004927 clay Substances 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000000084 colloidal system Substances 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
239000000306 component Substances 0.000 description 1
239000002131 composite material Substances 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
235000009508 confectionery Nutrition 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
150000004696 coordination complex Chemical class 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
230000037029 cross reaction Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
230000002559 cytogenic effect Effects 0.000 description 1
GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
108020001096 dihydrofolate reductase Proteins 0.000 description 1
102000006795 dihydrofolate reductase activity proteins Human genes 0.000 description 1
108040000939 dihydrofolate reductase activity proteins Proteins 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
239000000539 dimer Substances 0.000 description 1
NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
VFNGKCDDZUSWLR-UHFFFAOYSA-L disulfate(2-) Chemical compound [O-]S(=O)(=O)OS([O-])(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-L 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
230000003828 downregulation Effects 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
235000013399 edible fruits Nutrition 0.000 description 1
235000014103 egg white Nutrition 0.000 description 1
210000000969 egg white Anatomy 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
230000007368 endocrine function Effects 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
HPWMACWMMZPMSS-UHFFFAOYSA-N ethane;sulfuric acid Chemical compound CC.OS(O)(=O)=O HPWMACWMMZPMSS-UHFFFAOYSA-N 0.000 description 1
ROAYSRAUMPWBQX-UHFFFAOYSA-N ethanol;sulfuric acid Chemical compound CCO.OS(O)(=O)=O ROAYSRAUMPWBQX-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000004744 fabric Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
235000013305 food Nutrition 0.000 description 1
150000004675 formic acid derivatives Chemical class 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
229940080345 gamma-cyclodextrin Drugs 0.000 description 1
GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
238000010353 genetic engineering Methods 0.000 description 1
150000002300 glucoheptoses Chemical class 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
235000009424 haa Nutrition 0.000 description 1
238000011134 hematopoietic stem cell transplantation Methods 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
108700000056 herpes simplex virus ORF P Proteins 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000001165 hydrophobic group Chemical group 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
229940071676 hydroxypropylcellulose Drugs 0.000 description 1
201000008980 hyperinsulinism Diseases 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000002649 immunization Methods 0.000 description 1
238000003365 immunocytochemistry Methods 0.000 description 1
238000009399 inbreeding Methods 0.000 description 1
229910052738 indium Inorganic materials 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
229940068935 insulin-like growth factor 2 Drugs 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
101150109249 lacI gene Proteins 0.000 description 1
230000006651 lactation Effects 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
230000000527 lymphocytic effect Effects 0.000 description 1
230000002101 lytic effect Effects 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940099273 magnesium trisilicate Drugs 0.000 description 1
229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
235000019793 magnesium trisilicate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
239000002905 metal composite material Substances 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
LRPCLTPZMUIPFK-UHFFFAOYSA-N methane;sulfuric acid Chemical compound C.OS(O)(=O)=O LRPCLTPZMUIPFK-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
229940042472 mineral oil Drugs 0.000 description 1
230000033607 mismatch repair Effects 0.000 description 1
230000002073 mitogenetic effect Effects 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
239000013642 negative control Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000007899 nucleic acid hybridization Methods 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
125000003835 nucleoside group Chemical group 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
101150110245 ompC gene Proteins 0.000 description 1
101150073640 ompF gene Proteins 0.000 description 1
101150093139 ompT gene Proteins 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000012856 packing Methods 0.000 description 1
210000004923 pancreatic tissue Anatomy 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
101150050446 pelB gene Proteins 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
CTYRPMDGLDAWRQ-UHFFFAOYSA-N phenyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1=CC=CC=C1 CTYRPMDGLDAWRQ-UHFFFAOYSA-N 0.000 description 1
101150009573 phoA gene Proteins 0.000 description 1
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
230000003234 polygenic effect Effects 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000004302 potassium sorbate Substances 0.000 description 1
235000010241 potassium sorbate Nutrition 0.000 description 1
229940069338 potassium sorbate Drugs 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
244000144977 poultry Species 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
108010070945 proinsulin-like growth factor II Proteins 0.000 description 1
AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
238000001814 protein method Methods 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
238000013139 quantization Methods 0.000 description 1
238000005956 quaternization reaction Methods 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000002994 raw material Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
229940100618 rectal suppository Drugs 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
230000008521 reorganization Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
238000003757 reverse transcription PCR Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 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
210000004706 scrotum Anatomy 0.000 description 1
238000003196 serial analysis of gene expression Methods 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
229940007115 shark cartilage extract Drugs 0.000 description 1
238000010008 shearing Methods 0.000 description 1
230000003584 silencer Effects 0.000 description 1
230000037432 silent mutation Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000003068 static effect Effects 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
238000005728 strengthening Methods 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
150000003573 thiols Chemical group 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
229940038773 trisodium citrate Drugs 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1