EA032675B1 - Способ и композиции для лечения болезни альцгеймера и других таупатий - Google Patents

Info

Publication number

EA032675B1

EA032675B1 EA201171397A EA201171397A EA032675B1 EA 032675 B1 EA032675 B1 EA 032675B1 EA 201171397 A EA201171397 A EA 201171397A EA 201171397 A EA201171397 A EA 201171397A EA 032675 B1 EA032675 B1 EA 032675B1

Authority

EA

Eurasian Patent Office

Prior art keywords

tau

patient

immunogenic

amino acid

acid sequence

Prior art date

2009-06-10

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 93
• 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 60
• 208000034799 Tauopathies Diseases 0.000 title claims abstract description 12
• 239000000203 mixture Substances 0.000 title abstract description 12
• 102000013498 tau Proteins Human genes 0.000 claims abstract description 242
• 108010026424 tau Proteins Proteins 0.000 claims abstract description 242
• 101000854943 Enterobacteria phage T4 Valyl-tRNA ligase modifier Proteins 0.000 claims abstract description 189
• 230000002163 immunogen Effects 0.000 claims abstract description 129
• 210000004556 brain Anatomy 0.000 claims abstract description 40
• 230000003542 behavioural effect Effects 0.000 claims abstract description 19
• 108090000623 proteins and genes Proteins 0.000 claims description 104
• 230000001575 pathological effect Effects 0.000 claims description 60
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 59
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 56
• 230000007170 pathology Effects 0.000 claims description 39
• 239000002671 adjuvant Substances 0.000 claims description 37
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
• 201000010099 disease Diseases 0.000 claims description 29
• -1 a-synuclein Proteins 0.000 claims description 22
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 22
• 239000003153 chemical reaction reagent Substances 0.000 claims description 19
• 239000012634 fragment Substances 0.000 claims description 17
• 206010012289 Dementia Diseases 0.000 claims description 14
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 13
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 13
• 230000000890 antigenic effect Effects 0.000 claims description 13
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 11
• 238000001727 in vivo Methods 0.000 claims description 9
• 238000001514 detection method Methods 0.000 claims description 8
• 230000000750 progressive effect Effects 0.000 claims description 8
• 239000000523 sample Substances 0.000 claims description 8
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 7
• 206010034010 Parkinsonism Diseases 0.000 claims description 7
• 102000009091 Amyloidogenic Proteins Human genes 0.000 claims description 6
• 108010048112 Amyloidogenic Proteins Proteins 0.000 claims description 6
• 201000010374 Down Syndrome Diseases 0.000 claims description 6
• 102000029797 Prion Human genes 0.000 claims description 6
• 108091000054 Prion Proteins 0.000 claims description 6
• 210000000349 chromosome Anatomy 0.000 claims description 6
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
• 206010003694 Atrophy Diseases 0.000 claims description 5
• 230000037444 atrophy Effects 0.000 claims description 5
• 239000012472 biological sample Substances 0.000 claims description 4
• 239000002243 precursor Substances 0.000 claims description 4
• 230000009885 systemic effect Effects 0.000 claims description 4
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 3
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 3
• 238000009007 Diagnostic Kit Methods 0.000 claims description 3
• 206010018341 Gliosis Diseases 0.000 claims description 3
• 201000002481 Myositis Diseases 0.000 claims description 3
• 206010002022 amyloidosis Diseases 0.000 claims description 3
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
• 230000002308 calcification Effects 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 230000007387 gliosis Effects 0.000 claims description 3
• 230000002739 subcortical effect Effects 0.000 claims description 3
• 101800001288 Atrial natriuretic factor Proteins 0.000 claims description 2
• 101800001890 Atrial natriuretic peptide Proteins 0.000 claims description 2
• 102400001282 Atrial natriuretic peptide Human genes 0.000 claims description 2
• 102000055006 Calcitonin Human genes 0.000 claims description 2
• 108060001064 Calcitonin Proteins 0.000 claims description 2
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 2
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 2
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 2
• 102000012192 Cystatin C Human genes 0.000 claims description 2
• 108010061642 Cystatin C Proteins 0.000 claims description 2
• 102000004878 Gelsolin Human genes 0.000 claims description 2
• 108090001064 Gelsolin Proteins 0.000 claims description 2
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 2
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 2
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 claims description 2
• 102100027670 Islet amyloid polypeptide Human genes 0.000 claims description 2
• 108010063045 Lactoferrin Proteins 0.000 claims description 2
• 102000010445 Lactoferrin Human genes 0.000 claims description 2
• 102000016943 Muramidase Human genes 0.000 claims description 2
• 108010014251 Muramidase Proteins 0.000 claims description 2
• 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims description 2
• 108010071690 Prealbumin Proteins 0.000 claims description 2
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims description 2
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims description 2
• 102100021398 Transforming growth factor-beta-induced protein ig-h3 Human genes 0.000 claims description 2
• 108700006666 betaIG-H3 Proteins 0.000 claims description 2
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 2
• 229960004015 calcitonin Drugs 0.000 claims description 2
• NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 claims description 2
• CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 2
• 229940078795 lactoferrin Drugs 0.000 claims description 2
• 235000021242 lactoferrin Nutrition 0.000 claims description 2
• 239000004325 lysozyme Substances 0.000 claims description 2
• 229960000274 lysozyme Drugs 0.000 claims description 2
• 235000010335 lysozyme Nutrition 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 230000001024 immunotherapeutic effect Effects 0.000 claims 2
• 230000006269 (delayed) early viral mRNA transcription Effects 0.000 claims 1
• 102000005666 Apolipoprotein A-I Human genes 0.000 claims 1
• 108010059886 Apolipoprotein A-I Proteins 0.000 claims 1
• 102000009081 Apolipoprotein A-II Human genes 0.000 claims 1
• 108010087614 Apolipoprotein A-II Proteins 0.000 claims 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 1
• 102000011782 Keratins Human genes 0.000 claims 1
• 108010076876 Keratins Proteins 0.000 claims 1
• 241000940612 Medina Species 0.000 claims 1
• 102000003946 Prolactin Human genes 0.000 claims 1
• 108010057464 Prolactin Proteins 0.000 claims 1
• 102100029290 Transthyretin Human genes 0.000 claims 1
• 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
• 102000015736 beta 2-Microglobulin Human genes 0.000 claims 1
• 108010081355 beta 2-Microglobulin Proteins 0.000 claims 1
• 229940124465 diagnostic for alzheimer's disease Drugs 0.000 claims 1
• 230000003274 myotonic effect Effects 0.000 claims 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims 1
• 229940097325 prolactin Drugs 0.000 claims 1
• 238000010188 recombinant method Methods 0.000 claims 1
• 208000018726 traumatic encephalopathy Diseases 0.000 claims 1
• 230000001737 promoting effect Effects 0.000 abstract 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 124
• 241000699670 Mus sp. Species 0.000 description 111
• 230000026731 phosphorylation Effects 0.000 description 104
• 238000006366 phosphorylation reaction Methods 0.000 description 104
• 235000018102 proteins Nutrition 0.000 description 94
• 102000004169 proteins and genes Human genes 0.000 description 94
• 239000002253 acid Substances 0.000 description 86
• 235000003704 aspartic acid Nutrition 0.000 description 86
• 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 86
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 86
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 43
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 42
• 102100022033 Presenilin-1 Human genes 0.000 description 38
• 238000012360 testing method Methods 0.000 description 38
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 37
• 230000003053 immunization Effects 0.000 description 37
• 238000002649 immunization Methods 0.000 description 37
• 108010029020 prolylglycine Proteins 0.000 description 35
• 241001465754 Metazoa Species 0.000 description 32
• 235000013922 glutamic acid Nutrition 0.000 description 31
• 239000004220 glutamic acid Substances 0.000 description 31
• 238000011282 treatment Methods 0.000 description 28
• 210000003027 ear inner Anatomy 0.000 description 27
• 230000003161 proteinsynthetic effect Effects 0.000 description 26
• 238000002347 injection Methods 0.000 description 25
• 239000007924 injection Substances 0.000 description 25
• 101001071233 Homo sapiens PHD finger protein 1 Proteins 0.000 description 24
• 102100036879 PHD finger protein 1 Human genes 0.000 description 24
• 108010026333 seryl-proline Proteins 0.000 description 24
• 238000009169 immunotherapy Methods 0.000 description 23
• 238000010172 mouse model Methods 0.000 description 22
• 241000282414 Homo sapiens Species 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 20
• 239000003814 drug Substances 0.000 description 20
• 241000699666 Mus <mouse, genus> Species 0.000 description 19
• RNKSNIBMTUYWSH-YFKPBYRVSA-N L-prolylglycine Chemical compound [O-]C(=O)CNC(=O)[C@@H]1CCC[NH2+]1 RNKSNIBMTUYWSH-YFKPBYRVSA-N 0.000 description 18
• DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 18
• XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 18
• 230000028993 immune response Effects 0.000 description 17
• 235000001014 amino acid Nutrition 0.000 description 16
• 229940024606 amino acid Drugs 0.000 description 16
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 15
• 230000035508 accumulation Effects 0.000 description 15
• 238000009825 accumulation Methods 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 15
• 210000002381 plasma Anatomy 0.000 description 15
• 230000004044 response Effects 0.000 description 15
• 230000001225 therapeutic effect Effects 0.000 description 15
• 239000013598 vector Substances 0.000 description 15
• 238000011161 development Methods 0.000 description 14
• 230000018109 developmental process Effects 0.000 description 14
• 229940079593 drug Drugs 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 210000001519 tissue Anatomy 0.000 description 14
• IWAXHBCACVWNHT-BQBZGAKWSA-N Gly-Asp-Arg Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IWAXHBCACVWNHT-BQBZGAKWSA-N 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 12
• 150000001413 amino acids Chemical class 0.000 description 12
• 108091007433 antigens Proteins 0.000 description 12
• 102000036639 antigens Human genes 0.000 description 12
• 230000035772 mutation Effects 0.000 description 12
• 238000002965 ELISA Methods 0.000 description 11
• OQPNSDWGAMFJNU-QWRGUYRKSA-N Ser-Gly-Tyr Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OQPNSDWGAMFJNU-QWRGUYRKSA-N 0.000 description 11
• 108010055044 Tetanus Toxin Proteins 0.000 description 11
• 230000005875 antibody response Effects 0.000 description 11
• 239000000427 antigen Substances 0.000 description 11
• 108010077112 prolyl-proline Proteins 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• 229940118376 tetanus toxin Drugs 0.000 description 11
• QVOGDCQNGLBNCR-FXQIFTODSA-N Ser-Arg-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O QVOGDCQNGLBNCR-FXQIFTODSA-N 0.000 description 10
• 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 description 10
• 210000004369 blood Anatomy 0.000 description 10
• 239000008280 blood Substances 0.000 description 10
• VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 10
• 230000004770 neurodegeneration Effects 0.000 description 10
• PMNHJLASAAWELO-FOHZUACHSA-N Gly-Asp-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PMNHJLASAAWELO-FOHZUACHSA-N 0.000 description 9
• 108060003951 Immunoglobulin Proteins 0.000 description 9
• 241000699660 Mus musculus Species 0.000 description 9
• 210000001947 dentate gyrus Anatomy 0.000 description 9
• 150000002308 glutamine derivatives Chemical class 0.000 description 9
• 102000018358 immunoglobulin Human genes 0.000 description 9
• 108010057821 leucylproline Proteins 0.000 description 9
• 238000002560 therapeutic procedure Methods 0.000 description 9
• 238000011830 transgenic mouse model Methods 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 8
• FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 8
• 230000002776 aggregation Effects 0.000 description 8
• 238000004220 aggregation Methods 0.000 description 8
• 229940037003 alum Drugs 0.000 description 8
• 238000013459 approach Methods 0.000 description 8
• 239000002502 liposome Substances 0.000 description 8
• 108010031719 prolyl-serine Proteins 0.000 description 8
• 230000008685 targeting Effects 0.000 description 8
• 238000002255 vaccination Methods 0.000 description 8
• HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 7
• VENMDXUVHSKEIN-GUBZILKMSA-N Arg-Ser-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VENMDXUVHSKEIN-GUBZILKMSA-N 0.000 description 7
• 241001529936 Murinae Species 0.000 description 7
• HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 7
• PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 7
• CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 7
• DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 7
• KERCOYANYUPLHJ-XGEHTFHBSA-N Thr-Pro-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O KERCOYANYUPLHJ-XGEHTFHBSA-N 0.000 description 7
• 239000000969 carrier Substances 0.000 description 7
• 230000003247 decreasing effect Effects 0.000 description 7
• 230000001965 increasing effect Effects 0.000 description 7
• 108010060857 isoleucyl-valyl-tyrosine Proteins 0.000 description 7
• 230000033001 locomotion Effects 0.000 description 7
• 108010064235 lysylglycine Proteins 0.000 description 7
• 108010054155 lysyllysine Proteins 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 7
• 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 7
• 239000000243 solution Substances 0.000 description 7
• 238000010186 staining Methods 0.000 description 7
• KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 6
• LBRCLQMZAHRTLV-ZKWXMUAHSA-N Ile-Gly-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LBRCLQMZAHRTLV-ZKWXMUAHSA-N 0.000 description 6
• VTJUNIYRYIAIHF-IUCAKERBSA-N Leu-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O VTJUNIYRYIAIHF-IUCAKERBSA-N 0.000 description 6
• FHJQROWZEJFZPO-SRVKXCTJSA-N Pro-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FHJQROWZEJFZPO-SRVKXCTJSA-N 0.000 description 6
• 241000700605 Viruses Species 0.000 description 6
• 230000000875 corresponding effect Effects 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 6
• 108010089804 glycyl-threonine Proteins 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 229940035032 monophosphoryl lipid a Drugs 0.000 description 6
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 6
• 210000002569 neuron Anatomy 0.000 description 6
• 108020004707 nucleic acids Proteins 0.000 description 6
• 102000039446 nucleic acids Human genes 0.000 description 6
• 150000007523 nucleic acids Chemical class 0.000 description 6
• 238000001543 one-way ANOVA Methods 0.000 description 6
• 108010004914 prolylarginine Proteins 0.000 description 6
• 238000011321 prophylaxis Methods 0.000 description 6
• 235000004400 serine Nutrition 0.000 description 6
• 108010003885 valyl-prolyl-glycyl-glycine Proteins 0.000 description 6
• 238000001262 western blot Methods 0.000 description 6
• SUHLZMHFRALVSY-YUMQZZPRSA-N Ala-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)NCC(O)=O SUHLZMHFRALVSY-YUMQZZPRSA-N 0.000 description 5
• OINVDEKBKBCPLX-JXUBOQSCSA-N Ala-Lys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OINVDEKBKBCPLX-JXUBOQSCSA-N 0.000 description 5
• 101001071234 Arabidopsis thaliana SEC12-like protein 1 Proteins 0.000 description 5
• 241000894006 Bacteria Species 0.000 description 5
• 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 5
• 102000014914 Carrier Proteins Human genes 0.000 description 5
• 241000702421 Dependoparvovirus Species 0.000 description 5
• ABPRMMYHROQBLY-NKWVEPMBSA-N Gly-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)CN)C(=O)O ABPRMMYHROQBLY-NKWVEPMBSA-N 0.000 description 5
• 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 5
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
• PWPBLZXWFXJFHE-RHYQMDGZSA-N Leu-Pro-Thr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O PWPBLZXWFXJFHE-RHYQMDGZSA-N 0.000 description 5
• IVFUVMSKSFSFBT-NHCYSSNCSA-N Lys-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN IVFUVMSKSFSFBT-NHCYSSNCSA-N 0.000 description 5
• SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 5
• 108010036933 Presenilin-1 Proteins 0.000 description 5
• BODDREDDDRZUCF-QTKMDUPCSA-N Pro-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]2CCCN2)O BODDREDDDRZUCF-QTKMDUPCSA-N 0.000 description 5
• MHHQQZIFLWFZGR-DCAQKATOSA-N Pro-Lys-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O MHHQQZIFLWFZGR-DCAQKATOSA-N 0.000 description 5
• 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 description 5
• LNICFEXCAHIJOR-DCAQKATOSA-N Pro-Ser-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LNICFEXCAHIJOR-DCAQKATOSA-N 0.000 description 5
• PKHDJFHFMGQMPS-RCWTZXSCSA-N Pro-Thr-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PKHDJFHFMGQMPS-RCWTZXSCSA-N 0.000 description 5
• MUARUIBTKQJKFY-WHFBIAKZSA-N Ser-Gly-Asp Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MUARUIBTKQJKFY-WHFBIAKZSA-N 0.000 description 5
• KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 5
• NUEHQDHDLDXCRU-GUBZILKMSA-N Ser-Pro-Arg Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NUEHQDHDLDXCRU-GUBZILKMSA-N 0.000 description 5
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
• RTJPAGFXOWEBAI-SRVKXCTJSA-N Val-Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RTJPAGFXOWEBAI-SRVKXCTJSA-N 0.000 description 5
• 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 5
• 108010005233 alanylglutamic acid Proteins 0.000 description 5
• 108010087924 alanylproline Proteins 0.000 description 5
• 230000002238 attenuated effect Effects 0.000 description 5
• 230000001580 bacterial effect Effects 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 230000001149 cognitive effect Effects 0.000 description 5
• 238000002648 combination therapy Methods 0.000 description 5
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
• 230000009760 functional impairment Effects 0.000 description 5
• 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 5
• 102000057063 human MAPT Human genes 0.000 description 5
• 239000003550 marker Substances 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 208000015122 neurodegenerative disease Diseases 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 238000012549 training Methods 0.000 description 5
• 241000701161 unidentified adenovirus Species 0.000 description 5
• 229960005486 vaccine Drugs 0.000 description 5
• BUANFPRKJKJSRR-ACZMJKKPSA-N Ala-Ala-Gln Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CCC(N)=O BUANFPRKJKJSRR-ACZMJKKPSA-N 0.000 description 4
• ZFXQNADNEBRERM-BJDJZHNGSA-N Ala-Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 ZFXQNADNEBRERM-BJDJZHNGSA-N 0.000 description 4
• FSBCNCKIQZZASN-GUBZILKMSA-N Ala-Arg-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O FSBCNCKIQZZASN-GUBZILKMSA-N 0.000 description 4
• YAXNATKKPOWVCP-ZLUOBGJFSA-N Ala-Asn-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O YAXNATKKPOWVCP-ZLUOBGJFSA-N 0.000 description 4
• WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 4
• LMFXXZPPZDCPTA-ZKWXMUAHSA-N Ala-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N LMFXXZPPZDCPTA-ZKWXMUAHSA-N 0.000 description 4
• QUIGLPSHIFPEOV-CIUDSAMLSA-N Ala-Lys-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O QUIGLPSHIFPEOV-CIUDSAMLSA-N 0.000 description 4
• 206010002027 Amyotrophy Diseases 0.000 description 4
• 206010003062 Apraxia Diseases 0.000 description 4
• RKRSYHCNPFGMTA-CIUDSAMLSA-N Arg-Glu-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O RKRSYHCNPFGMTA-CIUDSAMLSA-N 0.000 description 4
• NVFSJIXJZCDICF-SRVKXCTJSA-N Asp-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N NVFSJIXJZCDICF-SRVKXCTJSA-N 0.000 description 4
• 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 4
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
• KUTPGXNAAOQSPD-LPEHRKFASA-N Glu-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O KUTPGXNAAOQSPD-LPEHRKFASA-N 0.000 description 4
• MTAOBYXRYJZRGQ-WDSKDSINSA-N Glu-Gly-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MTAOBYXRYJZRGQ-WDSKDSINSA-N 0.000 description 4
• BEQGFMIBZFNROK-JGVFFNPUSA-N Gly-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)CN)C(=O)O BEQGFMIBZFNROK-JGVFFNPUSA-N 0.000 description 4
• OHUKZZYSJBKFRR-WHFBIAKZSA-N Gly-Ser-Asp Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O OHUKZZYSJBKFRR-WHFBIAKZSA-N 0.000 description 4
• YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 4
• LVXFNTIIGOQBMD-SRVKXCTJSA-N His-Leu-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O LVXFNTIIGOQBMD-SRVKXCTJSA-N 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• CYHYBSGMHMHKOA-CIQUZCHMSA-N Ile-Ala-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CYHYBSGMHMHKOA-CIQUZCHMSA-N 0.000 description 4
• UCGDDTHMMVWVMV-FSPLSTOPSA-N Ile-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(O)=O UCGDDTHMMVWVMV-FSPLSTOPSA-N 0.000 description 4
• KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 4
• CIVKXGPFXDIQBV-WDCWCFNPSA-N Leu-Gln-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CIVKXGPFXDIQBV-WDCWCFNPSA-N 0.000 description 4
• FMEICTQWUKNAGC-YUMQZZPRSA-N Leu-Gly-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O FMEICTQWUKNAGC-YUMQZZPRSA-N 0.000 description 4
• REPBGZHJKYWFMJ-KKUMJFAQSA-N Leu-Lys-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N REPBGZHJKYWFMJ-KKUMJFAQSA-N 0.000 description 4
• AAORVPFVUIHEAB-YUMQZZPRSA-N Lys-Asp-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O AAORVPFVUIHEAB-YUMQZZPRSA-N 0.000 description 4
• RLZDUFRBMQNYIJ-YUMQZZPRSA-N Lys-Cys-Gly Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N RLZDUFRBMQNYIJ-YUMQZZPRSA-N 0.000 description 4
• GIKFNMZSGYAPEJ-HJGDQZAQSA-N Lys-Thr-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O GIKFNMZSGYAPEJ-HJGDQZAQSA-N 0.000 description 4
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
• 102000029749 Microtubule Human genes 0.000 description 4
• 108091022875 Microtubule Proteins 0.000 description 4
• 108010079364 N-glycylalanine Proteins 0.000 description 4
• 229920005372 Plexiglas® Polymers 0.000 description 4
• HJSCRFZVGXAGNG-SRVKXCTJSA-N Pro-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1 HJSCRFZVGXAGNG-SRVKXCTJSA-N 0.000 description 4
• AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 108010003201 RGH 0205 Proteins 0.000 description 4
• YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 4
• LVHHEVGYAZGXDE-KDXUFGMBSA-N Thr-Ala-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(=O)O)N)O LVHHEVGYAZGXDE-KDXUFGMBSA-N 0.000 description 4
• CQNFRKAKGDSJFR-NUMRIWBASA-N Thr-Glu-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O CQNFRKAKGDSJFR-NUMRIWBASA-N 0.000 description 4
• IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 4
• JAKHAONCJJZVHT-DCAQKATOSA-N Val-Lys-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N JAKHAONCJJZVHT-DCAQKATOSA-N 0.000 description 4
• 108010047495 alanylglycine Proteins 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• 108010013835 arginine glutamate Proteins 0.000 description 4
• 108010040443 aspartyl-aspartic acid Proteins 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 230000006399 behavior Effects 0.000 description 4
• 239000012620 biological material Substances 0.000 description 4
• 210000000133 brain stem Anatomy 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 230000019771 cognition Effects 0.000 description 4
• 108010016616 cysteinylglycine Proteins 0.000 description 4
• 230000007850 degeneration Effects 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 238000001415 gene therapy Methods 0.000 description 4
• 108010049041 glutamylalanine Proteins 0.000 description 4
• 210000002443 helper t lymphocyte Anatomy 0.000 description 4
• 108010025306 histidylleucine Proteins 0.000 description 4
• 229940072221 immunoglobulins Drugs 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 210000004688 microtubule Anatomy 0.000 description 4
• 238000002823 phage display Methods 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 230000000069 prophylactic effect Effects 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 238000012216 screening Methods 0.000 description 4
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
• 210000002966 serum Anatomy 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 241000894007 species Species 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• 108010061238 threonyl-glycine Proteins 0.000 description 4
• YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 102000007469 Actins Human genes 0.000 description 3
• 108010085238 Actins Proteins 0.000 description 3
• NINQYGGNRIBFSC-CIUDSAMLSA-N Ala-Lys-Ser Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CO)C(O)=O NINQYGGNRIBFSC-CIUDSAMLSA-N 0.000 description 3
• YHBDGLZYNIARKJ-GUBZILKMSA-N Ala-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N YHBDGLZYNIARKJ-GUBZILKMSA-N 0.000 description 3
• 206010059245 Angiopathy Diseases 0.000 description 3
• SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 3
• ZYPWIUFLYMQZBS-SRVKXCTJSA-N Asn-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ZYPWIUFLYMQZBS-SRVKXCTJSA-N 0.000 description 3
• SDHFVYLZFBDSQT-DCAQKATOSA-N Asp-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N SDHFVYLZFBDSQT-DCAQKATOSA-N 0.000 description 3
• CELPEWWLSXMVPH-CIUDSAMLSA-N Asp-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O CELPEWWLSXMVPH-CIUDSAMLSA-N 0.000 description 3
• VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 3
• SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 3
• SVABRQFIHCSNCI-FOHZUACHSA-N Asp-Gly-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O SVABRQFIHCSNCI-FOHZUACHSA-N 0.000 description 3
• CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 3
• GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 description 3
• 102100021277 Beta-secretase 2 Human genes 0.000 description 3
• 101710150190 Beta-secretase 2 Proteins 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 108010039939 Cell Wall Skeleton Proteins 0.000 description 3
• 150000008574 D-amino acids Chemical group 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• RKAQZCDMSUQTSS-FXQIFTODSA-N Gln-Asp-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RKAQZCDMSUQTSS-FXQIFTODSA-N 0.000 description 3
• FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 3
• FQCILXROGNOZON-YUMQZZPRSA-N Gln-Pro-Gly Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O FQCILXROGNOZON-YUMQZZPRSA-N 0.000 description 3
• JDUKCSSHWNIQQZ-IHRRRGAJSA-N Glu-Phe-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O JDUKCSSHWNIQQZ-IHRRRGAJSA-N 0.000 description 3
• BFEZQZKEPRKKHV-SRVKXCTJSA-N Glu-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O BFEZQZKEPRKKHV-SRVKXCTJSA-N 0.000 description 3
• DDXZHOHEABQXSE-NKIYYHGXSA-N Glu-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O DDXZHOHEABQXSE-NKIYYHGXSA-N 0.000 description 3
• PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 3
• MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 3
• QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 3
• CCBIBMKQNXHNIN-ZETCQYMHSA-N Gly-Leu-Gly Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CCBIBMKQNXHNIN-ZETCQYMHSA-N 0.000 description 3
• FHQRLHFYVZAQHU-IUCAKERBSA-N Gly-Lys-Gln Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O FHQRLHFYVZAQHU-IUCAKERBSA-N 0.000 description 3
• MYXNLWDWWOTERK-BHNWBGBOSA-N Gly-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN)O MYXNLWDWWOTERK-BHNWBGBOSA-N 0.000 description 3
• TVTZEOHWHUVYCG-KYNKHSRBSA-N Gly-Thr-Thr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O TVTZEOHWHUVYCG-KYNKHSRBSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• CCHSQWLCOOZREA-GMOBBJLQSA-N Ile-Asp-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)O)N CCHSQWLCOOZREA-GMOBBJLQSA-N 0.000 description 3
• AMSYMDIIIRJRKZ-HJPIBITLSA-N Ile-His-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N AMSYMDIIIRJRKZ-HJPIBITLSA-N 0.000 description 3
• QSXSHZIRKTUXNG-STECZYCISA-N Ile-Val-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QSXSHZIRKTUXNG-STECZYCISA-N 0.000 description 3
• DLCOFDAHNMMQPP-SRVKXCTJSA-N Leu-Asp-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DLCOFDAHNMMQPP-SRVKXCTJSA-N 0.000 description 3
• WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 3
• SPCHLZUWJTYZFC-IHRRRGAJSA-N Lys-His-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(O)=O SPCHLZUWJTYZFC-IHRRRGAJSA-N 0.000 description 3
• SLQJJFAVWSZLBL-BJDJZHNGSA-N Lys-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN SLQJJFAVWSZLBL-BJDJZHNGSA-N 0.000 description 3
• QQPSCXKFDSORFT-IHRRRGAJSA-N Lys-Lys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN QQPSCXKFDSORFT-IHRRRGAJSA-N 0.000 description 3
• WQDKIVRHTQYJSN-DCAQKATOSA-N Lys-Ser-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WQDKIVRHTQYJSN-DCAQKATOSA-N 0.000 description 3
• JMNRXRPBHFGXQX-GUBZILKMSA-N Lys-Ser-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JMNRXRPBHFGXQX-GUBZILKMSA-N 0.000 description 3
• ZUGVARDEGWMMLK-SRVKXCTJSA-N Lys-Ser-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN ZUGVARDEGWMMLK-SRVKXCTJSA-N 0.000 description 3
• WZVSHTFTCYOFPL-GARJFASQSA-N Lys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCCN)N)C(=O)O WZVSHTFTCYOFPL-GARJFASQSA-N 0.000 description 3
• YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 3
• VWPJQIHBBOJWDN-DCAQKATOSA-N Lys-Val-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O VWPJQIHBBOJWDN-DCAQKATOSA-N 0.000 description 3
• ONGCSGVHCSAATF-CIUDSAMLSA-N Met-Ala-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O ONGCSGVHCSAATF-CIUDSAMLSA-N 0.000 description 3
• MTBVQFFQMXHCPC-CIUDSAMLSA-N Met-Glu-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MTBVQFFQMXHCPC-CIUDSAMLSA-N 0.000 description 3
• 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 3
• OQTDZEJJWWAGJT-KKUMJFAQSA-N Phe-Lys-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O OQTDZEJJWWAGJT-KKUMJFAQSA-N 0.000 description 3
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 3
• HPXVFFIIGOAQRV-DCAQKATOSA-N Pro-Arg-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O HPXVFFIIGOAQRV-DCAQKATOSA-N 0.000 description 3
• BNBBNGZZKQUWCD-IUCAKERBSA-N Pro-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H]1CCCN1 BNBBNGZZKQUWCD-IUCAKERBSA-N 0.000 description 3
• QBFONMUYNSNKIX-AVGNSLFASA-N Pro-Arg-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QBFONMUYNSNKIX-AVGNSLFASA-N 0.000 description 3
• WFIVLLFYUZZWOD-RHYQMDGZSA-N Pro-Lys-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WFIVLLFYUZZWOD-RHYQMDGZSA-N 0.000 description 3
• ANESFYPBAJPYNJ-SDDRHHMPSA-N Pro-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 ANESFYPBAJPYNJ-SDDRHHMPSA-N 0.000 description 3
• RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 description 3
• KDBHVPXBQADZKY-GUBZILKMSA-N Pro-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KDBHVPXBQADZKY-GUBZILKMSA-N 0.000 description 3
• FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 3
• IURWWZYKYPEANQ-HJGDQZAQSA-N Pro-Thr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IURWWZYKYPEANQ-HJGDQZAQSA-N 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 3
• OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 3
• MIJWOJAXARLEHA-WDSKDSINSA-N Ser-Gly-Glu Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O MIJWOJAXARLEHA-WDSKDSINSA-N 0.000 description 3
• FPCGZYMRFFIYIH-CIUDSAMLSA-N Ser-Lys-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O FPCGZYMRFFIYIH-CIUDSAMLSA-N 0.000 description 3
• FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 3
• HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 3
• HYLXOQURIOCKIH-VQVTYTSYSA-N Thr-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N HYLXOQURIOCKIH-VQVTYTSYSA-N 0.000 description 3
• NOWXWJLVGTVJKM-PBCZWWQYSA-N Thr-Asp-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O NOWXWJLVGTVJKM-PBCZWWQYSA-N 0.000 description 3
• LGNBRHZANHMZHK-NUMRIWBASA-N Thr-Glu-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O LGNBRHZANHMZHK-NUMRIWBASA-N 0.000 description 3
• QOLYAJSZHIJCTO-VQVTYTSYSA-N Thr-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O QOLYAJSZHIJCTO-VQVTYTSYSA-N 0.000 description 3
• MUAFDCVOHYAFNG-RCWTZXSCSA-N Thr-Pro-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MUAFDCVOHYAFNG-RCWTZXSCSA-N 0.000 description 3
• GVMXJJAJLIEASL-ZJDVBMNYSA-N Thr-Pro-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVMXJJAJLIEASL-ZJDVBMNYSA-N 0.000 description 3
• PGEFRHBWGOJPJT-KKUMJFAQSA-N Tyr-Lys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O PGEFRHBWGOJPJT-KKUMJFAQSA-N 0.000 description 3
• UMSZZGTXGKHTFJ-SRVKXCTJSA-N Tyr-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 UMSZZGTXGKHTFJ-SRVKXCTJSA-N 0.000 description 3
• DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 3
• VLOYGOZDPGYWFO-LAEOZQHASA-N Val-Asp-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VLOYGOZDPGYWFO-LAEOZQHASA-N 0.000 description 3
• YODDULVCGFQRFZ-ZKWXMUAHSA-N Val-Asp-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O YODDULVCGFQRFZ-ZKWXMUAHSA-N 0.000 description 3
• PWRITNSESKQTPW-NRPADANISA-N Val-Gln-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N PWRITNSESKQTPW-NRPADANISA-N 0.000 description 3
• LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 230000006978 adaptation Effects 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 108091008324 binding proteins Proteins 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 229940098773 bovine serum albumin Drugs 0.000 description 3
• 210000004520 cell wall skeleton Anatomy 0.000 description 3
• 208000010877 cognitive disease Diseases 0.000 description 3
• 230000007370 cognitive improvement Effects 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 238000003745 diagnosis Methods 0.000 description 3
• PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 210000003414 extremity Anatomy 0.000 description 3
• 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 108010036413 histidylglycine Proteins 0.000 description 3
• 230000002519 immonomodulatory effect Effects 0.000 description 3
• 239000003022 immunostimulating agent Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 230000003834 intracellular effect Effects 0.000 description 3
• 238000007917 intracranial administration Methods 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 108010071185 leucyl-alanine Proteins 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000015654 memory Effects 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 201000000050 myeloid neoplasm Diseases 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 229940023041 peptide vaccine Drugs 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 3
• 108091033319 polynucleotide Proteins 0.000 description 3
• 102000040430 polynucleotide Human genes 0.000 description 3
• 239000002157 polynucleotide Substances 0.000 description 3
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
• 229920000053 polysorbate 80 Polymers 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 108010093296 prolyl-prolyl-alanine Proteins 0.000 description 3
• 230000009257 reactivity Effects 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 238000003259 recombinant expression Methods 0.000 description 3
• 230000000717 retained effect Effects 0.000 description 3
• 230000001177 retroviral effect Effects 0.000 description 3
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
• 229940081974 saccharin Drugs 0.000 description 3
• 235000019204 saccharin Nutrition 0.000 description 3
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 3
• 230000006403 short-term memory Effects 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 229940031439 squalene Drugs 0.000 description 3
• TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 3
• 230000000087 stabilizing effect Effects 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 230000002195 synergetic effect Effects 0.000 description 3
• 231100000331 toxic Toxicity 0.000 description 3
• 230000002588 toxic effect Effects 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• AXFMEGAFCUULFV-BLFANLJRSA-N (2s)-2-[[(2s)-1-[(2s,3r)-2-amino-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]pentanedioic acid Chemical compound CC[C@@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AXFMEGAFCUULFV-BLFANLJRSA-N 0.000 description 2
• RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 2
• WDIYWDJLXOCGRW-ACZMJKKPSA-N Ala-Asp-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WDIYWDJLXOCGRW-ACZMJKKPSA-N 0.000 description 2
• KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 2
• GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 2
• BTBUEVAGZCKULD-XPUUQOCRSA-N Ala-Gly-His Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BTBUEVAGZCKULD-XPUUQOCRSA-N 0.000 description 2
• QXRNAOYBCYVZCD-BQBZGAKWSA-N Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN QXRNAOYBCYVZCD-BQBZGAKWSA-N 0.000 description 2
• ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 2
• QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 2
• 102100026882 Alpha-synuclein Human genes 0.000 description 2
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
• NVCIXQYNWYTLDO-IHRRRGAJSA-N Arg-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCN=C(N)N)N NVCIXQYNWYTLDO-IHRRRGAJSA-N 0.000 description 2
• GNYUVVJYGJFKHN-RVMXOQNASA-N Arg-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N GNYUVVJYGJFKHN-RVMXOQNASA-N 0.000 description 2
• IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 description 2
• DNLQVHBBMPZUGJ-BQBZGAKWSA-N Arg-Ser-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O DNLQVHBBMPZUGJ-BQBZGAKWSA-N 0.000 description 2
• LLQIAIUAKGNOSE-NHCYSSNCSA-N Arg-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N LLQIAIUAKGNOSE-NHCYSSNCSA-N 0.000 description 2
• IARGXWMWRFOQPG-GCJQMDKQSA-N Asn-Ala-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IARGXWMWRFOQPG-GCJQMDKQSA-N 0.000 description 2
• KWBQPGIYEZKDEG-FSPLSTOPSA-N Asn-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O KWBQPGIYEZKDEG-FSPLSTOPSA-N 0.000 description 2
• LTDGPJKGJDIBQD-LAEOZQHASA-N Asn-Val-Gln Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LTDGPJKGJDIBQD-LAEOZQHASA-N 0.000 description 2
• PQKSVQSMTHPRIB-ZKWXMUAHSA-N Asn-Val-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O PQKSVQSMTHPRIB-ZKWXMUAHSA-N 0.000 description 2
• HPNDBHLITCHRSO-WHFBIAKZSA-N Asp-Ala-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)NCC(O)=O HPNDBHLITCHRSO-WHFBIAKZSA-N 0.000 description 2
• VPPXTHJNTYDNFJ-CIUDSAMLSA-N Asp-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N VPPXTHJNTYDNFJ-CIUDSAMLSA-N 0.000 description 2
• BUVNWKQBMZLCDW-UGYAYLCHSA-N Asp-Asn-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BUVNWKQBMZLCDW-UGYAYLCHSA-N 0.000 description 2
• VHQOCWWKXIOAQI-WDSKDSINSA-N Asp-Gln-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O VHQOCWWKXIOAQI-WDSKDSINSA-N 0.000 description 2
• VFUXXFVCYZPOQG-WDSKDSINSA-N Asp-Glu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VFUXXFVCYZPOQG-WDSKDSINSA-N 0.000 description 2
• YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 2
• ILQCHXURSRRIRY-YUMQZZPRSA-N Asp-His-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)O)N ILQCHXURSRRIRY-YUMQZZPRSA-N 0.000 description 2
• UMHUHHJMEXNSIV-CIUDSAMLSA-N Asp-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UMHUHHJMEXNSIV-CIUDSAMLSA-N 0.000 description 2
• 108010078791 Carrier Proteins Proteins 0.000 description 2
• 102000011727 Caspases Human genes 0.000 description 2
• 108010076667 Caspases Proteins 0.000 description 2
• 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 2
• 101000746263 Conus leopardus Conotoxin Lp5.1 Proteins 0.000 description 2
• 102100037364 Craniofacial development protein 1 Human genes 0.000 description 2
• XTHUKRLJRUVVBF-WHFBIAKZSA-N Cys-Gly-Ser Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O XTHUKRLJRUVVBF-WHFBIAKZSA-N 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• RGAOLBZBLOJUTP-GRLWGSQLSA-N Gln-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H](CCC(=O)N)N RGAOLBZBLOJUTP-GRLWGSQLSA-N 0.000 description 2
• PAOHIZNRJNIXQY-XQXXSGGOSA-N Gln-Thr-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PAOHIZNRJNIXQY-XQXXSGGOSA-N 0.000 description 2
• VLOLPWWCNKWRNB-LOKLDPHHSA-N Gln-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O VLOLPWWCNKWRNB-LOKLDPHHSA-N 0.000 description 2
• BBFCMGBMYIAGRS-AUTRQRHGSA-N Gln-Val-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O BBFCMGBMYIAGRS-AUTRQRHGSA-N 0.000 description 2
• XXCDTYBVGMPIOA-FXQIFTODSA-N Glu-Asp-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XXCDTYBVGMPIOA-FXQIFTODSA-N 0.000 description 2
• CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 2
• GXMXPCXXKVWOSM-KQXIARHKSA-N Glu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N GXMXPCXXKVWOSM-KQXIARHKSA-N 0.000 description 2
• INGJLBQKTRJLFO-UKJIMTQDSA-N Glu-Ile-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O INGJLBQKTRJLFO-UKJIMTQDSA-N 0.000 description 2
• HMJULNMJWOZNFI-XHNCKOQMSA-N Glu-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N)C(=O)O HMJULNMJWOZNFI-XHNCKOQMSA-N 0.000 description 2
• ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 2
• SCCPDJAQCXWPTF-VKHMYHEASA-N Gly-Asp Chemical compound NCC(=O)N[C@H](C(O)=O)CC(O)=O SCCPDJAQCXWPTF-VKHMYHEASA-N 0.000 description 2
• CQZDZKRHFWJXDF-WDSKDSINSA-N Gly-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CN CQZDZKRHFWJXDF-WDSKDSINSA-N 0.000 description 2
• AQLHORCVPGXDJW-IUCAKERBSA-N Gly-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN AQLHORCVPGXDJW-IUCAKERBSA-N 0.000 description 2
• QPTNELDXWKRIFX-YFKPBYRVSA-N Gly-Gly-Gln Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O QPTNELDXWKRIFX-YFKPBYRVSA-N 0.000 description 2
• YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 2
• INLIXXRWNUKVCF-JTQLQIEISA-N Gly-Gly-Tyr Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 INLIXXRWNUKVCF-JTQLQIEISA-N 0.000 description 2
• ALOBJFDJTMQQPW-ONGXEEELSA-N Gly-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)CN ALOBJFDJTMQQPW-ONGXEEELSA-N 0.000 description 2
• LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 2
• OQQKUTVULYLCDG-ONGXEEELSA-N Gly-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CN)C(O)=O OQQKUTVULYLCDG-ONGXEEELSA-N 0.000 description 2
• SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 2
• VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-N 0.000 description 2
• POJJAZJHBGXEGM-YUMQZZPRSA-N Gly-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN POJJAZJHBGXEGM-YUMQZZPRSA-N 0.000 description 2
• FOKISINOENBSDM-WLTAIBSBSA-N Gly-Thr-Tyr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O FOKISINOENBSDM-WLTAIBSBSA-N 0.000 description 2
• 101710154606 Hemagglutinin Proteins 0.000 description 2
• CZVQSYNVUHAILZ-UWVGGRQHSA-N His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 CZVQSYNVUHAILZ-UWVGGRQHSA-N 0.000 description 2
• TTYKEFZRLKQTHH-MELADBBJSA-N His-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O TTYKEFZRLKQTHH-MELADBBJSA-N 0.000 description 2
• FBOMZVOKCZMDIG-XQQFMLRXSA-N His-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N FBOMZVOKCZMDIG-XQQFMLRXSA-N 0.000 description 2
• GBMSSORHVHAYLU-QTKMDUPCSA-N His-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC1=CN=CN1)N)O GBMSSORHVHAYLU-QTKMDUPCSA-N 0.000 description 2
• 101000880187 Homo sapiens Craniofacial development protein 1 Proteins 0.000 description 2
• 101000875401 Homo sapiens Sterol 26-hydroxylase, mitochondrial Proteins 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
• FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 2
• UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 2
• 241000880493 Leptailurus serval Species 0.000 description 2
• HSQGMTRYSIHDAC-BQBZGAKWSA-N Leu-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(O)=O HSQGMTRYSIHDAC-BQBZGAKWSA-N 0.000 description 2
• ZURHXHNAEJJRNU-CIUDSAMLSA-N Leu-Asp-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZURHXHNAEJJRNU-CIUDSAMLSA-N 0.000 description 2
• JQSXWJXBASFONF-KKUMJFAQSA-N Leu-Asp-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JQSXWJXBASFONF-KKUMJFAQSA-N 0.000 description 2
• HVHRPWQEQHIQJF-AVGNSLFASA-N Leu-Lys-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HVHRPWQEQHIQJF-AVGNSLFASA-N 0.000 description 2
• ODRREERHVHMIPT-OEAJRASXSA-N Leu-Thr-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ODRREERHVHMIPT-OEAJRASXSA-N 0.000 description 2
• FLCMXEFCTLXBTL-DCAQKATOSA-N Lys-Asp-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N FLCMXEFCTLXBTL-DCAQKATOSA-N 0.000 description 2
• HGNRJCINZYHNOU-LURJTMIESA-N Lys-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(O)=O HGNRJCINZYHNOU-LURJTMIESA-N 0.000 description 2
• MUXNCRWTWBMNHX-SRVKXCTJSA-N Lys-Leu-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O MUXNCRWTWBMNHX-SRVKXCTJSA-N 0.000 description 2
• OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 2
• GAHJXEMYXKLZRQ-AJNGGQMLSA-N Lys-Lys-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O GAHJXEMYXKLZRQ-AJNGGQMLSA-N 0.000 description 2
• PDIDTSZKKFEDMB-UWVGGRQHSA-N Lys-Pro-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O PDIDTSZKKFEDMB-UWVGGRQHSA-N 0.000 description 2
• YSPZCHGIWAQVKQ-AVGNSLFASA-N Lys-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN YSPZCHGIWAQVKQ-AVGNSLFASA-N 0.000 description 2
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
• 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 2
• 108010002311 N-glycylglutamic acid Proteins 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 208000012902 Nervous system disease Diseases 0.000 description 2
• 208000025966 Neurological disease Diseases 0.000 description 2
• 208000014060 Niemann-Pick disease Diseases 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
• MPGJIHFJCXTVEX-KKUMJFAQSA-N Phe-Arg-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O MPGJIHFJCXTVEX-KKUMJFAQSA-N 0.000 description 2
• 241000223960 Plasmodium falciparum Species 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• FYQSMXKJYTZYRP-DCAQKATOSA-N Pro-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 FYQSMXKJYTZYRP-DCAQKATOSA-N 0.000 description 2
• HMNSRTLZAJHSIK-YUMQZZPRSA-N Pro-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 HMNSRTLZAJHSIK-YUMQZZPRSA-N 0.000 description 2
• NMELOOXSGDRBRU-YUMQZZPRSA-N Pro-Glu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 NMELOOXSGDRBRU-YUMQZZPRSA-N 0.000 description 2
• JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 description 2
• RVQDZELMXZRSSI-IUCAKERBSA-N Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 RVQDZELMXZRSSI-IUCAKERBSA-N 0.000 description 2
• LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 description 2
• AFWBWPCXSWUCLB-WDSKDSINSA-N Pro-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H]1CCC[NH2+]1 AFWBWPCXSWUCLB-WDSKDSINSA-N 0.000 description 2
• 101710176177 Protein A56 Proteins 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
• RZEQTVHJZCIUBT-WDSKDSINSA-N Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RZEQTVHJZCIUBT-WDSKDSINSA-N 0.000 description 2
• TYYBJUYSTWJHGO-ZKWXMUAHSA-N Ser-Asn-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O TYYBJUYSTWJHGO-ZKWXMUAHSA-N 0.000 description 2
• KNZQGAUEYZJUSQ-ZLUOBGJFSA-N Ser-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N KNZQGAUEYZJUSQ-ZLUOBGJFSA-N 0.000 description 2
• UOLGINIHBRIECN-FXQIFTODSA-N Ser-Glu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UOLGINIHBRIECN-FXQIFTODSA-N 0.000 description 2
• QKQDTEYDEIJPNK-GUBZILKMSA-N Ser-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO QKQDTEYDEIJPNK-GUBZILKMSA-N 0.000 description 2
• ZIFYDQAFEMIZII-GUBZILKMSA-N Ser-Leu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZIFYDQAFEMIZII-GUBZILKMSA-N 0.000 description 2
• XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 2
• JLPMFVAIQHCBDC-CIUDSAMLSA-N Ser-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N JLPMFVAIQHCBDC-CIUDSAMLSA-N 0.000 description 2
• PMCMLDNPAZUYGI-DCAQKATOSA-N Ser-Lys-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PMCMLDNPAZUYGI-DCAQKATOSA-N 0.000 description 2
• AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 2
• SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 2
• PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 2
• KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 2
• ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 2
• 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• FQPQPTHMHZKGFM-XQXXSGGOSA-N Thr-Ala-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O FQPQPTHMHZKGFM-XQXXSGGOSA-N 0.000 description 2
• MQBTXMPQNCGSSZ-OSUNSFLBSA-N Thr-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CCCN=C(N)N MQBTXMPQNCGSSZ-OSUNSFLBSA-N 0.000 description 2
• LMMDEZPNUTZJAY-GCJQMDKQSA-N Thr-Asp-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O LMMDEZPNUTZJAY-GCJQMDKQSA-N 0.000 description 2
• BECPPKYKPSRKCP-ZDLURKLDSA-N Thr-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O BECPPKYKPSRKCP-ZDLURKLDSA-N 0.000 description 2
• BVOVIGCHYNFJBZ-JXUBOQSCSA-N Thr-Leu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O BVOVIGCHYNFJBZ-JXUBOQSCSA-N 0.000 description 2
• LHNNQVXITHUCAB-QTKMDUPCSA-N Thr-Met-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O LHNNQVXITHUCAB-QTKMDUPCSA-N 0.000 description 2
• MXDOAJQRJBMGMO-FJXKBIBVSA-N Thr-Pro-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O MXDOAJQRJBMGMO-FJXKBIBVSA-N 0.000 description 2
• IQPWNQRRAJHOKV-KATARQTJSA-N Thr-Ser-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN IQPWNQRRAJHOKV-KATARQTJSA-N 0.000 description 2
• NDZYTIMDOZMECO-SHGPDSBTSA-N Thr-Thr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O NDZYTIMDOZMECO-SHGPDSBTSA-N 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• CPTQYHDSVGVGDZ-UKJIMTQDSA-N Val-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N CPTQYHDSVGVGDZ-UKJIMTQDSA-N 0.000 description 2
• PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 2
• RLVTVHSDKHBFQP-ULQDDVLXSA-N Val-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 RLVTVHSDKHBFQP-ULQDDVLXSA-N 0.000 description 2
• 230000005856 abnormality Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 238000007792 addition Methods 0.000 description 2
• 230000032683 aging Effects 0.000 description 2
• KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
• 108090000185 alpha-Synuclein Proteins 0.000 description 2
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
• 210000004727 amygdala Anatomy 0.000 description 2
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
• 230000000692 anti-sense effect Effects 0.000 description 2
• 229940009098 aspartate Drugs 0.000 description 2
• 108010069205 aspartyl-phenylalanine Proteins 0.000 description 2
• 108010038633 aspartylglutamate Proteins 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000007910 cell fusion Effects 0.000 description 2
• 210000002421 cell wall Anatomy 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 230000003930 cognitive ability Effects 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 208000017004 dementia pugilistica Diseases 0.000 description 2
• 230000008021 deposition Effects 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 238000001962 electrophoresis Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
• XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 2
• 108010010096 glycyl-glycyl-tyrosine Proteins 0.000 description 2
• 108010050848 glycylleucine Proteins 0.000 description 2
• 108010087823 glycyltyrosine Proteins 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000000185 hemagglutinin Substances 0.000 description 2
• 108010040030 histidinoalanine Proteins 0.000 description 2
• 230000001900 immune effect Effects 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 230000016784 immunoglobulin production Effects 0.000 description 2
• 238000003364 immunohistochemistry Methods 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000010255 intramuscular injection Methods 0.000 description 2
• 239000007927 intramuscular injection Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 230000002147 killing effect Effects 0.000 description 2
• 238000011813 knockout mouse model Methods 0.000 description 2
• 230000006742 locomotor activity Effects 0.000 description 2
• 210000004698 lymphocyte Anatomy 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 2
• 229960005225 mifamurtide Drugs 0.000 description 2
• 230000003278 mimic effect Effects 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 230000004973 motor coordination Effects 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000002702 ribosome display Methods 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 150000003568 thioethers Chemical class 0.000 description 2
• 108010072986 threonyl-seryl-lysine Proteins 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 231100000765 toxin Toxicity 0.000 description 2
• 108700012359 toxins Proteins 0.000 description 2
• 230000014616 translation Effects 0.000 description 2
• 102000003390 tumor necrosis factor Human genes 0.000 description 2
• 238000007492 two-way ANOVA Methods 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• 108010073969 valyllysine Proteins 0.000 description 2
• 108010021889 valylvaline Proteins 0.000 description 2
• 230000003442 weekly effect Effects 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N &alpha;-D-glucopyranosyl-&alpha;-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• DPUJVBNLRHXFMP-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;periodic acid Chemical compound OI(=O)(=O)=O.NCCCC[C@H](N)C(O)=O DPUJVBNLRHXFMP-JEDNCBNOSA-N 0.000 description 1
• UHPQFNXOFFPHJW-UHFFFAOYSA-N (4-methylphenyl)-phenylmethanamine Chemical compound C1=CC(C)=CC=C1C(N)C1=CC=CC=C1 UHPQFNXOFFPHJW-UHFFFAOYSA-N 0.000 description 1
• OLCFWQNMCDUEMF-UHFFFAOYSA-N 2,3-dihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carboxylic acid Chemical compound C1=C(C)C=C2C(C(C)C)=C(O)C(O)=C(C(O)=O)C2=C1 OLCFWQNMCDUEMF-UHFFFAOYSA-N 0.000 description 1
• YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
• 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
• 206010050013 Abulia Diseases 0.000 description 1
• 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• VBRDBGCROKWTPV-XHNCKOQMSA-N Ala-Glu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N VBRDBGCROKWTPV-XHNCKOQMSA-N 0.000 description 1
• NHWYNIZWLJYZAG-XVYDVKMFSA-N Ala-Ser-His Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N NHWYNIZWLJYZAG-XVYDVKMFSA-N 0.000 description 1
• IOFVWPYSRSCWHI-JXUBOQSCSA-N Ala-Thr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)N IOFVWPYSRSCWHI-JXUBOQSCSA-N 0.000 description 1
• 241000710929 Alphavirus Species 0.000 description 1
• 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
• 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
• 101800001718 Amyloid-beta protein Proteins 0.000 description 1
• 235000005749 Anthriscus sylvestris Nutrition 0.000 description 1
• 108010032595 Antibody Binding Sites Proteins 0.000 description 1
• 206010002942 Apathy Diseases 0.000 description 1
• 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
• AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 1
• MJINRRBEMOLJAK-DCAQKATOSA-N Arg-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N MJINRRBEMOLJAK-DCAQKATOSA-N 0.000 description 1
• ZEBDYGZVMMKZNB-SRVKXCTJSA-N Arg-Met-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCN=C(N)N)N ZEBDYGZVMMKZNB-SRVKXCTJSA-N 0.000 description 1
• KMCRKVOLRCOMBG-DJFWLOJKSA-N Asn-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KMCRKVOLRCOMBG-DJFWLOJKSA-N 0.000 description 1
• IBLAOXSULLECQZ-IUKAMOBKSA-N Asn-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(N)=O IBLAOXSULLECQZ-IUKAMOBKSA-N 0.000 description 1
• YVXRYLVELQYAEQ-SRVKXCTJSA-N Asn-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N YVXRYLVELQYAEQ-SRVKXCTJSA-N 0.000 description 1
• FAEIQWHBRBWUBN-FXQIFTODSA-N Asp-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N FAEIQWHBRBWUBN-FXQIFTODSA-N 0.000 description 1
• XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 description 1
• PZXPWHFYZXTFBI-YUMQZZPRSA-N Asp-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PZXPWHFYZXTFBI-YUMQZZPRSA-N 0.000 description 1
• LDGUZSIPGSPBJP-XVYDVKMFSA-N Asp-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)O)N LDGUZSIPGSPBJP-XVYDVKMFSA-N 0.000 description 1
• DYDKXJWQCIVTMR-WDSKDSINSA-N Asp-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O DYDKXJWQCIVTMR-WDSKDSINSA-N 0.000 description 1
• DJCAHYVLMSRBFR-QXEWZRGKSA-N Asp-Met-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O DJCAHYVLMSRBFR-QXEWZRGKSA-N 0.000 description 1
• JUWISGAGWSDGDH-KKUMJFAQSA-N Asp-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=CC=C1 JUWISGAGWSDGDH-KKUMJFAQSA-N 0.000 description 1
• HRVQDZOWMLFAOD-BIIVOSGPSA-N Asp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N)C(=O)O HRVQDZOWMLFAOD-BIIVOSGPSA-N 0.000 description 1
• NTQDELBZOMWXRS-IWGUZYHVSA-N Asp-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O NTQDELBZOMWXRS-IWGUZYHVSA-N 0.000 description 1
• RKXVTTIQNKPCHU-KKHAAJSZSA-N Asp-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O RKXVTTIQNKPCHU-KKHAAJSZSA-N 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 241000588832 Bordetella pertussis Species 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 101100228200 Caenorhabditis elegans gly-5 gene Proteins 0.000 description 1
• 102000003895 Calpain-1 Human genes 0.000 description 1
• 108090000236 Calpain-1 Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 229920001661 Chitosan Polymers 0.000 description 1
• 241000606161 Chlamydia Species 0.000 description 1
• 108010049048 Cholera Toxin Proteins 0.000 description 1
• 102000009016 Cholera Toxin Human genes 0.000 description 1
• 241000193449 Clostridium tetani Species 0.000 description 1
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
• 241000975300 Concholepas concholepas Species 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 1
• 102100023419 Cystic fibrosis transmembrane conductance regulator Human genes 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• YVGGHNCTFXOJCH-UHFFFAOYSA-N DDT Chemical compound C1=CC(Cl)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(Cl)C=C1 YVGGHNCTFXOJCH-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 239000003155 DNA primer Substances 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 206010013142 Disinhibition Diseases 0.000 description 1
• 101710181478 Envelope glycoprotein GP350 Proteins 0.000 description 1
• 241000588722 Escherichia Species 0.000 description 1
• 101000740487 Escherichia coli M-agglutinin Proteins 0.000 description 1
• 206010015548 Euthanasia Diseases 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000009123 Fibrin Human genes 0.000 description 1
• 108010073385 Fibrin Proteins 0.000 description 1
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
• 102000002090 Fibronectin type III Human genes 0.000 description 1
• 108050009401 Fibronectin type III Proteins 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 241000724791 Filamentous phage Species 0.000 description 1
• 102000001267 GSK3 Human genes 0.000 description 1
• 206010017577 Gait disturbance Diseases 0.000 description 1
• 206010056696 Gaze palsy Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• INKFLNZBTSNFON-CIUDSAMLSA-N Gln-Ala-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O INKFLNZBTSNFON-CIUDSAMLSA-N 0.000 description 1
• SXGMGNZEHFORAV-IUCAKERBSA-N Gln-Lys-Gly Chemical compound C(CCN)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N SXGMGNZEHFORAV-IUCAKERBSA-N 0.000 description 1
• KPNWAJMEMRCLAL-GUBZILKMSA-N Gln-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N KPNWAJMEMRCLAL-GUBZILKMSA-N 0.000 description 1
• AKDOUBMVLRCHBD-SIUGBPQLSA-N Gln-Tyr-Ile 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]([C@@H](C)CC)C(O)=O AKDOUBMVLRCHBD-SIUGBPQLSA-N 0.000 description 1
• UBRQJXFDVZNYJP-AVGNSLFASA-N Gln-Tyr-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O UBRQJXFDVZNYJP-AVGNSLFASA-N 0.000 description 1
• RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
• ZOXBSICWUDAOHX-GUBZILKMSA-N Glu-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCC(O)=O ZOXBSICWUDAOHX-GUBZILKMSA-N 0.000 description 1
• DSPQRJXOIXHOHK-WDSKDSINSA-N Glu-Asp-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O DSPQRJXOIXHOHK-WDSKDSINSA-N 0.000 description 1
• WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 1
• AIGROOHQXCACHL-WDSKDSINSA-N Glu-Gly-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O AIGROOHQXCACHL-WDSKDSINSA-N 0.000 description 1
• ILWHFUZZCFYSKT-AVGNSLFASA-N Glu-Lys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ILWHFUZZCFYSKT-AVGNSLFASA-N 0.000 description 1
• CQAHWYDHKUWYIX-YUMQZZPRSA-N Glu-Pro-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O CQAHWYDHKUWYIX-YUMQZZPRSA-N 0.000 description 1
• DCBSZJJHOTXMHY-DCAQKATOSA-N Glu-Pro-Pro Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DCBSZJJHOTXMHY-DCAQKATOSA-N 0.000 description 1
• MXJYXYDREQWUMS-XKBZYTNZSA-N Glu-Thr-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O MXJYXYDREQWUMS-XKBZYTNZSA-N 0.000 description 1
• 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 1
• RLFSBAPJTYKSLG-WHFBIAKZSA-N Gly-Ala-Asp Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O RLFSBAPJTYKSLG-WHFBIAKZSA-N 0.000 description 1
• FUESBOMYALLFNI-VKHMYHEASA-N Gly-Asn Chemical compound NCC(=O)N[C@H](C(O)=O)CC(N)=O FUESBOMYALLFNI-VKHMYHEASA-N 0.000 description 1
• KMSGYZQRXPUKGI-BYPYZUCNSA-N Gly-Gly-Asn Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(N)=O KMSGYZQRXPUKGI-BYPYZUCNSA-N 0.000 description 1
• DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 description 1
• IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 description 1
• FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 description 1
• HAOUOFNNJJLVNS-BQBZGAKWSA-N Gly-Pro-Ser Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O HAOUOFNNJJLVNS-BQBZGAKWSA-N 0.000 description 1
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
• WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 1
• LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 1
• JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 1
• DNAZKGFYFRGZIH-QWRGUYRKSA-N Gly-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 DNAZKGFYFRGZIH-QWRGUYRKSA-N 0.000 description 1
• GBYYQVBXFVDJPJ-WLTAIBSBSA-N Gly-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)CN)O GBYYQVBXFVDJPJ-WLTAIBSBSA-N 0.000 description 1
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
• 239000012981 Hank's balanced salt solution Substances 0.000 description 1
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
• 101710165610 Heat-stable 19 kDa antigen Proteins 0.000 description 1
• 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• DCRODRAURLJOFY-XPUUQOCRSA-N His-Ala-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)NCC(O)=O DCRODRAURLJOFY-XPUUQOCRSA-N 0.000 description 1
• NELVFWFDOKRTOR-SDDRHHMPSA-N His-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O NELVFWFDOKRTOR-SDDRHHMPSA-N 0.000 description 1
• AKAPKBNIVNPIPO-KKUMJFAQSA-N His-His-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1NC=NC=1)C1=CN=CN1 AKAPKBNIVNPIPO-KKUMJFAQSA-N 0.000 description 1
• 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 1
• 101001009007 Homo sapiens Hemoglobin subunit alpha Proteins 0.000 description 1
• 101001109465 Homo sapiens NACHT, LRR and PYD domains-containing protein 3 Proteins 0.000 description 1
• 101001102158 Homo sapiens Phosphatidylserine synthase 1 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• FJWYJQRCVNGEAQ-ZPFDUUQYSA-N Ile-Asn-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N FJWYJQRCVNGEAQ-ZPFDUUQYSA-N 0.000 description 1
• MQFGXJNSUJTXDT-QSFUFRPTSA-N Ile-Gly-Ile Chemical compound N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)O MQFGXJNSUJTXDT-QSFUFRPTSA-N 0.000 description 1
• GMUYXHHJAGQHGB-TUBUOCAGSA-N Ile-Thr-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N GMUYXHHJAGQHGB-TUBUOCAGSA-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
• 108010065920 Insulin Lispro Proteins 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 108010065805 Interleukin-12 Proteins 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
• SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
• HFKJBCPRWWGPEY-BQBZGAKWSA-N L-arginyl-L-glutamic acid Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HFKJBCPRWWGPEY-BQBZGAKWSA-N 0.000 description 1
• ZUKPVRWZDMRIEO-VKHMYHEASA-N L-cysteinylglycine Chemical compound SC[C@H]([NH3+])C(=O)NCC([O-])=O ZUKPVRWZDMRIEO-VKHMYHEASA-N 0.000 description 1
• 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
• ZRLUISBDKUWAIZ-CIUDSAMLSA-N Leu-Ala-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O ZRLUISBDKUWAIZ-CIUDSAMLSA-N 0.000 description 1
• XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 1
• DUBAVOVZNZKEQQ-AVGNSLFASA-N Leu-Arg-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CCCN=C(N)N DUBAVOVZNZKEQQ-AVGNSLFASA-N 0.000 description 1
• JYOAXOMPIXKMKK-YUMQZZPRSA-N Leu-Gln Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CCC(N)=O JYOAXOMPIXKMKK-YUMQZZPRSA-N 0.000 description 1
• NFNVDJGXRFEYTK-YUMQZZPRSA-N Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O NFNVDJGXRFEYTK-YUMQZZPRSA-N 0.000 description 1
• HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 1
• LAPSXOAUPNOINL-YUMQZZPRSA-N Leu-Gly-Asp Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O LAPSXOAUPNOINL-YUMQZZPRSA-N 0.000 description 1
• WXUOJXIGOPMDJM-SRVKXCTJSA-N Leu-Lys-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O WXUOJXIGOPMDJM-SRVKXCTJSA-N 0.000 description 1
• KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 1
• CGHXMODRYJISSK-NHCYSSNCSA-N Leu-Val-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O CGHXMODRYJISSK-NHCYSSNCSA-N 0.000 description 1
• 239000000232 Lipid Bilayer Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• MPOHDJKRBLVGCT-CIUDSAMLSA-N Lys-Ala-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N MPOHDJKRBLVGCT-CIUDSAMLSA-N 0.000 description 1
• KPJJOZUXFOLGMQ-CIUDSAMLSA-N Lys-Asp-Asn Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N KPJJOZUXFOLGMQ-CIUDSAMLSA-N 0.000 description 1
• QBGPXOGXCVKULO-BQBZGAKWSA-N Lys-Cys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(O)=O QBGPXOGXCVKULO-BQBZGAKWSA-N 0.000 description 1
• DFXQCCBKGUNYGG-GUBZILKMSA-N Lys-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCCN DFXQCCBKGUNYGG-GUBZILKMSA-N 0.000 description 1
• XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
• IGRMTQMIDNDFAA-UWVGGRQHSA-N Lys-His Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IGRMTQMIDNDFAA-UWVGGRQHSA-N 0.000 description 1
• NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 description 1
• HVAUKHLDSDDROB-KKUMJFAQSA-N Lys-Lys-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HVAUKHLDSDDROB-KKUMJFAQSA-N 0.000 description 1
• SBQDRNOLGSYHQA-YUMQZZPRSA-N Lys-Ser-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SBQDRNOLGSYHQA-YUMQZZPRSA-N 0.000 description 1
• MIFFFXHMAHFACR-KATARQTJSA-N Lys-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN MIFFFXHMAHFACR-KATARQTJSA-N 0.000 description 1
• ZVXSESPJMKNIQA-YXMSTPNBSA-N Lys-Thr-Pro-Pro Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 ZVXSESPJMKNIQA-YXMSTPNBSA-N 0.000 description 1
• XABXVVSWUVCZST-GVXVVHGQSA-N Lys-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN XABXVVSWUVCZST-GVXVVHGQSA-N 0.000 description 1
• RIPJMCFGQHGHNP-RHYQMDGZSA-N Lys-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)N)O RIPJMCFGQHGHNP-RHYQMDGZSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 101150100676 Map2k1 gene Proteins 0.000 description 1
• 241000712079 Measles morbillivirus Species 0.000 description 1
• WYDFQSJOARJAMM-GUBZILKMSA-N Met-Pro-Asp Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WYDFQSJOARJAMM-GUBZILKMSA-N 0.000 description 1
• OVTOTTGZBWXLFU-QXEWZRGKSA-N Met-Val-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O OVTOTTGZBWXLFU-QXEWZRGKSA-N 0.000 description 1
• LBSWWNKMVPAXOI-GUBZILKMSA-N Met-Val-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O LBSWWNKMVPAXOI-GUBZILKMSA-N 0.000 description 1
• 241000237852 Mollusca Species 0.000 description 1
• 206010028403 Mutism Diseases 0.000 description 1
• 102100022691 NACHT, LRR and PYD domains-containing protein 3 Human genes 0.000 description 1
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
• 101100068676 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gln-1 gene Proteins 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• 108010058846 Ovalbumin Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 206010034703 Perseveration Diseases 0.000 description 1
• 206010034719 Personality change Diseases 0.000 description 1
• 241000502301 Pertusaria trachythallina Species 0.000 description 1
• HTTYNOXBBOWZTB-SRVKXCTJSA-N Phe-Asn-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N HTTYNOXBBOWZTB-SRVKXCTJSA-N 0.000 description 1
• LWPMGKSZPKFKJD-DZKIICNBSA-N Phe-Glu-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O LWPMGKSZPKFKJD-DZKIICNBSA-N 0.000 description 1
• MSSXKZBDKZAHCX-UNQGMJICSA-N Phe-Thr-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O MSSXKZBDKZAHCX-UNQGMJICSA-N 0.000 description 1
• 102100039298 Phosphatidylserine synthase 1 Human genes 0.000 description 1
• 108010001441 Phosphopeptides Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 208000036757 Postencephalitic parkinsonism Diseases 0.000 description 1
• 102000007584 Prealbumin Human genes 0.000 description 1
• 108010050254 Presenilins Proteins 0.000 description 1
• 208000024777 Prion disease Diseases 0.000 description 1
• SHAQGFGGJSLLHE-BQBZGAKWSA-N Pro-Gln Chemical compound NC(=O)CC[C@@H](C([O-])=O)NC(=O)[C@@H]1CCC[NH2+]1 SHAQGFGGJSLLHE-BQBZGAKWSA-N 0.000 description 1
• GURGCNUWVSDYTP-SRVKXCTJSA-N Pro-Leu-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GURGCNUWVSDYTP-SRVKXCTJSA-N 0.000 description 1
• WOIFYRZPIORBRY-AVGNSLFASA-N Pro-Lys-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O WOIFYRZPIORBRY-AVGNSLFASA-N 0.000 description 1
• MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 1
• GVUVRRPYYDHHGK-VQVTYTSYSA-N Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GVUVRRPYYDHHGK-VQVTYTSYSA-N 0.000 description 1
• KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 1
• OOZJHTXCLJUODH-QXEWZRGKSA-N Pro-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 OOZJHTXCLJUODH-QXEWZRGKSA-N 0.000 description 1
• ZMLRZBWCXPQADC-TUAOUCFPSA-N Pro-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 ZMLRZBWCXPQADC-TUAOUCFPSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
• 102000014961 Protein Precursors Human genes 0.000 description 1
• 108010078762 Protein Precursors Proteins 0.000 description 1
• 241000220317 Rosa Species 0.000 description 1
• 241000607142 Salmonella Species 0.000 description 1
• 241000242680 Schistosoma mansoni Species 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 206010039966 Senile dementia Diseases 0.000 description 1
• WTUJZHKANPDPIN-CIUDSAMLSA-N Ser-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N WTUJZHKANPDPIN-CIUDSAMLSA-N 0.000 description 1
• MESDJCNHLZBMEP-ZLUOBGJFSA-N Ser-Asp-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MESDJCNHLZBMEP-ZLUOBGJFSA-N 0.000 description 1
• GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 1
• BKZYBLLIBOBOOW-GHCJXIJMSA-N Ser-Ile-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O BKZYBLLIBOBOOW-GHCJXIJMSA-N 0.000 description 1
• NLOAIFSWUUFQFR-CIUDSAMLSA-N Ser-Leu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O NLOAIFSWUUFQFR-CIUDSAMLSA-N 0.000 description 1
• PPNPDKGQRFSCAC-CIUDSAMLSA-N Ser-Lys-Asp Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(O)=O)C(O)=O PPNPDKGQRFSCAC-CIUDSAMLSA-N 0.000 description 1
• LRWBCWGEUCKDTN-BJDJZHNGSA-N Ser-Lys-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LRWBCWGEUCKDTN-BJDJZHNGSA-N 0.000 description 1
• WGDYNRCOQRERLZ-KKUMJFAQSA-N Ser-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N WGDYNRCOQRERLZ-KKUMJFAQSA-N 0.000 description 1
• MHVXPTAMDHLTHB-IHPCNDPISA-N Ser-Phe-Trp Chemical compound C([C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 MHVXPTAMDHLTHB-IHPCNDPISA-N 0.000 description 1
• WBAXJMCUFIXCNI-WDSKDSINSA-N Ser-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WBAXJMCUFIXCNI-WDSKDSINSA-N 0.000 description 1
• RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 1
• CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 1
• PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 1
• LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
• 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 208000003028 Stuttering Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 108030001722 Tentoxilysin Proteins 0.000 description 1
• 206010043376 Tetanus Diseases 0.000 description 1
• OYTNZCBFDXGQGE-XQXXSGGOSA-N Thr-Gln-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C)C(=O)O)N)O OYTNZCBFDXGQGE-XQXXSGGOSA-N 0.000 description 1
• WXVIGTAUZBUDPZ-DTLFHODZSA-N Thr-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 WXVIGTAUZBUDPZ-DTLFHODZSA-N 0.000 description 1
• UUSQVWOVUYMLJA-PPCPHDFISA-N Thr-Lys-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UUSQVWOVUYMLJA-PPCPHDFISA-N 0.000 description 1
• GXDLGHLJTHMDII-WISUUJSJSA-N Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(O)=O GXDLGHLJTHMDII-WISUUJSJSA-N 0.000 description 1
• PELIQFPESHBTMA-WLTAIBSBSA-N Thr-Tyr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 PELIQFPESHBTMA-WLTAIBSBSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 108700019146 Transgenes Proteins 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• AOLHUMAVONBBEZ-STQMWFEESA-N Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AOLHUMAVONBBEZ-STQMWFEESA-N 0.000 description 1
• KGSDLCMCDFETHU-YESZJQIVSA-N Tyr-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O KGSDLCMCDFETHU-YESZJQIVSA-N 0.000 description 1
• 101150117115 V gene Proteins 0.000 description 1
• QRZVUAAKNRHEOP-GUBZILKMSA-N Val-Ala-Val Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O QRZVUAAKNRHEOP-GUBZILKMSA-N 0.000 description 1
• XXDVDTMEVBYRPK-XPUUQOCRSA-N Val-Gln Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O XXDVDTMEVBYRPK-XPUUQOCRSA-N 0.000 description 1
• UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 1
• JKHXYJKMNSSFFL-IUCAKERBSA-N Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN JKHXYJKMNSSFFL-IUCAKERBSA-N 0.000 description 1
• VENKIVFKIPGEJN-NHCYSSNCSA-N Val-Met-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N VENKIVFKIPGEJN-NHCYSSNCSA-N 0.000 description 1
• DEGUERSKQBRZMZ-FXQIFTODSA-N Val-Ser-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DEGUERSKQBRZMZ-FXQIFTODSA-N 0.000 description 1
• UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
• QTPQHINADBYBNA-DCAQKATOSA-N Val-Ser-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN QTPQHINADBYBNA-DCAQKATOSA-N 0.000 description 1
• UQMPYVLTQCGRSK-IFFSRLJSSA-N Val-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N)O UQMPYVLTQCGRSK-IFFSRLJSSA-N 0.000 description 1
• KRNYOVHEKOBTEF-YUMQZZPRSA-N Val-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(O)=O KRNYOVHEKOBTEF-YUMQZZPRSA-N 0.000 description 1
• 241000700647 Variola virus Species 0.000 description 1
• 241000711975 Vesicular stomatitis virus Species 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 108010056243 alanylalanine Proteins 0.000 description 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
• 230000003941 amyloidogenesis Effects 0.000 description 1
• 230000003942 amyloidogenic effect Effects 0.000 description 1
• 239000002269 analeptic agent Substances 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 150000004056 anthraquinones Chemical class 0.000 description 1
• 230000001130 anti-lysozyme effect Effects 0.000 description 1
• 210000000628 antibody-producing cell Anatomy 0.000 description 1
• 102000025171 antigen binding proteins Human genes 0.000 description 1
• 108091000831 antigen binding proteins Proteins 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 108010036533 arginylvaline Proteins 0.000 description 1
• 108010047857 aspartylglycine Proteins 0.000 description 1
• 230000007854 axonal transport deficit Effects 0.000 description 1
• 208000013404 behavioral symptom Diseases 0.000 description 1
• 238000009227 behaviour therapy Methods 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 230000002146 bilateral effect Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 238000010241 blood sampling Methods 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000010382 chemical cross-linking Methods 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 230000006999 cognitive decline Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 230000002281 colonystimulating effect Effects 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 210000004292 cytoskeleton Anatomy 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000010217 densitometric analysis Methods 0.000 description 1
• 229960003964 deoxycholic acid Drugs 0.000 description 1
• 238000009795 derivation Methods 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• 229960005156 digoxin Drugs 0.000 description 1
• 229960003983 diphtheria toxoid Drugs 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 238000007878 drug screening assay Methods 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• 230000000925 erythroid effect Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 102000015694 estrogen receptors Human genes 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 229950003499 fibrin Drugs 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 210000000245 forearm Anatomy 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 230000000799 fusogenic effect Effects 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 108010015792 glycyllysine Proteins 0.000 description 1
• 230000036449 good health Effects 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
• 108060003552 hemocyanin Proteins 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 108010028295 histidylhistidine Proteins 0.000 description 1
• 230000001744 histochemical effect Effects 0.000 description 1
• 230000028996 humoral immune response Effects 0.000 description 1
• 210000004408 hybridoma Anatomy 0.000 description 1
• 230000006951 hyperphosphorylation Effects 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 238000003018 immunoassay Methods 0.000 description 1
• 238000003119 immunoblot Methods 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 238000012151 immunohistochemical method Methods 0.000 description 1
• 230000002434 immunopotentiative effect Effects 0.000 description 1
• 239000003547 immunosorbent Substances 0.000 description 1
• 238000012744 immunostaining Methods 0.000 description 1
• 230000002637 immunotoxin Effects 0.000 description 1
• 239000002596 immunotoxin Substances 0.000 description 1
• 231100000608 immunotoxin Toxicity 0.000 description 1
• 229940051026 immunotoxin Drugs 0.000 description 1
• 238000011503 in vivo imaging Methods 0.000 description 1
• 210000003000 inclusion body Anatomy 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 108010078274 isoleucylvaline Proteins 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 108010034529 leucyl-lysine Proteins 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 108010003700 lysyl aspartic acid Proteins 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 210000005171 mammalian brain Anatomy 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 230000008774 maternal effect Effects 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 238000001000 micrograph Methods 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 208000027061 mild cognitive impairment Diseases 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 210000002161 motor neuron Anatomy 0.000 description 1
• 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 230000004118 muscle contraction Effects 0.000 description 1
• 230000001016 myotrophic effect Effects 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 230000001722 neurochemical effect Effects 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000007121 neuropathological change Effects 0.000 description 1
• 231100000189 neurotoxic Toxicity 0.000 description 1
• 230000002887 neurotoxic effect Effects 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 230000000508 neurotrophic effect Effects 0.000 description 1
• 238000011587 new zealand white rabbit Methods 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 229940092253 ovalbumin Drugs 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008055 phosphate buffer solution Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000000467 phytic acid Substances 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920002401 polyacrylamide Polymers 0.000 description 1
• 108010040003 polyglutamine Proteins 0.000 description 1
• 229920000155 polyglutamine Polymers 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 208000000170 postencephalitic Parkinson disease Diseases 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 108010070643 prolylglutamic acid Proteins 0.000 description 1
• 210000004129 prosencephalon Anatomy 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 201000000196 pseudobulbar palsy Diseases 0.000 description 1
• 238000004445 quantitative analysis Methods 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000012502 risk assessment Methods 0.000 description 1
• 230000004434 saccadic eye movement Effects 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 230000011218 segmentation Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 238000009987 spinning Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 238000011272 standard treatment Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229960002317 succinimide Drugs 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000011477 surgical intervention Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
• 229960000814 tetanus toxoid Drugs 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 108010051110 tyrosyl-lysine Proteins 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 210000002845 virion Anatomy 0.000 description 1
• 108010027345 wheylin-1 peptide Proteins 0.000 description 1