CA2434672C - Sfrp and peptide motifs that interact with sfrp and methods of their use - Google Patents

Info

Publication number

CA2434672C

CA2434672C CA2434672A CA2434672A CA2434672C CA 2434672 C CA2434672 C CA 2434672C CA 2434672 A CA2434672 A CA 2434672A CA 2434672 A CA2434672 A CA 2434672A CA 2434672 C CA2434672 C CA 2434672C

Authority

CA

Canada

Prior art keywords

sfrp

seq

amino acid

leu

acid sequence

Prior art date

2001-01-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 278
• 238000000034 method Methods 0.000 title claims abstract description 78
• 210000002997 osteoclast Anatomy 0.000 claims description 141
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 98
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 86
• 230000015572 biosynthetic process Effects 0.000 claims description 71
• 239000012634 fragment Substances 0.000 claims description 70
• 229920001184 polypeptide Polymers 0.000 claims description 66
• 230000004069 differentiation Effects 0.000 claims description 28
• 239000003446 ligand Substances 0.000 claims description 21
• 125000000539 amino acid group Chemical group 0.000 claims description 20
• 230000002401 inhibitory effect Effects 0.000 claims description 19
• 235000018417 cysteine Nutrition 0.000 claims description 11
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 210000000130 stem cell Anatomy 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 8
• 238000000338 in vitro Methods 0.000 claims description 6
• 238000001727 in vivo Methods 0.000 claims description 5
• 108091006084 receptor activators Proteins 0.000 claims description 5
• 102100030058 Secreted frizzled-related protein 1 Human genes 0.000 abstract description 210
• 108050007993 Secreted frizzled-related protein 1 Proteins 0.000 abstract description 205
• 108090000623 proteins and genes Proteins 0.000 abstract description 127
• 230000027455 binding Effects 0.000 abstract description 120
• 238000009739 binding Methods 0.000 abstract description 119
• 102000004169 proteins and genes Human genes 0.000 abstract description 117
• 230000003993 interaction Effects 0.000 abstract description 19
• 108010020277 WD repeat containing planar cell polarity effector Proteins 0.000 abstract description 9
• 230000001105 regulatory effect Effects 0.000 abstract description 7
• 102100030053 Secreted frizzled-related protein 3 Human genes 0.000 abstract description 5
• 235000018102 proteins Nutrition 0.000 description 109
• 210000004027 cell Anatomy 0.000 description 63
• 230000000694 effects Effects 0.000 description 55
• 239000000523 sample Substances 0.000 description 44
• 210000001744 T-lymphocyte Anatomy 0.000 description 34
• 235000001014 amino acid Nutrition 0.000 description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 33
• 238000002965 ELISA Methods 0.000 description 32
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 32
• 102100040247 Tumor necrosis factor Human genes 0.000 description 32
• 150000007523 nucleic acids Chemical class 0.000 description 32
• 150000001413 amino acids Chemical class 0.000 description 31
• 210000000988 bone and bone Anatomy 0.000 description 31
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 30
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 30
• 238000002474 experimental method Methods 0.000 description 29
• 102000037865 fusion proteins Human genes 0.000 description 29
• 108020001507 fusion proteins Proteins 0.000 description 29
• 201000010099 disease Diseases 0.000 description 28
• 230000014509 gene expression Effects 0.000 description 27
• 238000006467 substitution reaction Methods 0.000 description 26
• 210000000963 osteoblast Anatomy 0.000 description 23
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 22
• 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 22
• 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 22
• 150000001875 compounds Chemical class 0.000 description 22
• 229940098773 bovine serum albumin Drugs 0.000 description 20
• 230000001965 increasing effect Effects 0.000 description 20
• 210000004989 spleen cell Anatomy 0.000 description 19
• 238000011282 treatment Methods 0.000 description 19
• 108020004414 DNA Proteins 0.000 description 17
• 241000282414 Homo sapiens Species 0.000 description 17
• 108700012920 TNF Proteins 0.000 description 16
• 238000003752 polymerase chain reaction Methods 0.000 description 16
• 238000003501 co-culture Methods 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 14
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 14
• 230000006870 function Effects 0.000 description 14
• 108091028043 Nucleic acid sequence Proteins 0.000 description 13
• 239000003153 chemical reaction reagent Substances 0.000 description 13
• 102000039446 nucleic acids Human genes 0.000 description 13
• 108020004707 nucleic acids Proteins 0.000 description 13
• MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 description 12
• YHZQOSXDTFRZKU-WDSOQIARSA-N Arg-Trp-Leu Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N)=CNC2=C1 YHZQOSXDTFRZKU-WDSOQIARSA-N 0.000 description 12
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 12
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 12
• 108091034117 Oligonucleotide Proteins 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• 230000004927 fusion Effects 0.000 description 12
• 239000000203 mixture Substances 0.000 description 12
• 239000000243 solution Substances 0.000 description 12
• 210000001519 tissue Anatomy 0.000 description 12
• 239000013598 vector Substances 0.000 description 12
• 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 description 11
• 101710178436 Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 11
• 230000002159 abnormal effect Effects 0.000 description 11
• 235000010633 broth Nutrition 0.000 description 11
• 238000012217 deletion Methods 0.000 description 11
• 230000037430 deletion Effects 0.000 description 11
• 108010049041 glutamylalanine Proteins 0.000 description 11
• 108010050848 glycylleucine Proteins 0.000 description 11
• 210000005088 multinucleated cell Anatomy 0.000 description 11
• 239000002953 phosphate buffered saline Substances 0.000 description 11
• 108700026244 Open Reading Frames Proteins 0.000 description 10
• 239000002299 complementary DNA 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
• 108010034529 leucyl-lysine Proteins 0.000 description 10
• 208000002865 osteopetrosis Diseases 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000012216 screening Methods 0.000 description 10
• ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 9
• 108010079364 N-glycylalanine Proteins 0.000 description 9
• 208000001132 Osteoporosis Diseases 0.000 description 9
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• 230000001580 bacterial effect Effects 0.000 description 9
• -1 co-factors Substances 0.000 description 9
• 230000001419 dependent effect Effects 0.000 description 9
• 150000002611 lead compounds Chemical class 0.000 description 9
• 108010073969 valyllysine Proteins 0.000 description 9
• QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 9
• 235000005282 vitamin D3 Nutrition 0.000 description 9
• 239000011647 vitamin D3 Substances 0.000 description 9
• 229940021056 vitamin d3 Drugs 0.000 description 9
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 8
• 108050003627 Wnt Proteins 0.000 description 8
• 102000013814 Wnt Human genes 0.000 description 8
• 230000010072 bone remodeling Effects 0.000 description 8
• 230000007423 decrease Effects 0.000 description 8
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 8
• 239000012530 fluid Substances 0.000 description 8
• 230000004410 intraocular pressure Effects 0.000 description 8
• 230000000670 limiting effect Effects 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 238000011160 research Methods 0.000 description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 208000006386 Bone Resorption Diseases 0.000 description 7
• 101000864743 Homo sapiens Secreted frizzled-related protein 1 Proteins 0.000 description 7
• 102000014128 RANK Ligand Human genes 0.000 description 7
• 108010025832 RANK Ligand Proteins 0.000 description 7
• 230000024279 bone resorption Effects 0.000 description 7
• 210000004899 c-terminal region Anatomy 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 229960002986 dinoprostone Drugs 0.000 description 7
• 239000002773 nucleotide Substances 0.000 description 7
• 125000003729 nucleotide group Chemical group 0.000 description 7
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 6
• 108091007505 ADAM17 Proteins 0.000 description 6
• CFPQUJZTLUQUTJ-HTFCKZLJSA-N Ala-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)N CFPQUJZTLUQUTJ-HTFCKZLJSA-N 0.000 description 6
• IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 6
• JREOBWLIZLXRIS-GUBZILKMSA-N Asn-Glu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JREOBWLIZLXRIS-GUBZILKMSA-N 0.000 description 6
• 241000894006 Bacteria Species 0.000 description 6
• 208000020084 Bone disease Diseases 0.000 description 6
• PRXCTTWKGJAPMT-ZLUOBGJFSA-N Cys-Ala-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O PRXCTTWKGJAPMT-ZLUOBGJFSA-N 0.000 description 6
• 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 6
• OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 description 6
• DVLZZEPUNFEUBW-AVGNSLFASA-N Glu-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N DVLZZEPUNFEUBW-AVGNSLFASA-N 0.000 description 6
• PMSMKNYRZCKVMC-DRZSPHRISA-N Glu-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)N PMSMKNYRZCKVMC-DRZSPHRISA-N 0.000 description 6
• HHSKZJZWQFPSKN-AVGNSLFASA-N Glu-Tyr-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O HHSKZJZWQFPSKN-AVGNSLFASA-N 0.000 description 6
• 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 6
• LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 6
• RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 6
• DTPOVRRYXPJJAZ-FJXKBIBVSA-N Gly-Arg-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N DTPOVRRYXPJJAZ-FJXKBIBVSA-N 0.000 description 6
• JNGHLWWFPGIJER-STQMWFEESA-N Gly-Pro-Tyr Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JNGHLWWFPGIJER-STQMWFEESA-N 0.000 description 6
• 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 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 108010093488 His-His-His-His-His-His Proteins 0.000 description 6
• 102000000589 Interleukin-1 Human genes 0.000 description 6
• 108010002352 Interleukin-1 Proteins 0.000 description 6
• GPXFZVUVPCFTMG-AVGNSLFASA-N Leu-Arg-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(C)C GPXFZVUVPCFTMG-AVGNSLFASA-N 0.000 description 6
• VGPCJSXPPOQPBK-YUMQZZPRSA-N Leu-Gly-Ser Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O VGPCJSXPPOQPBK-YUMQZZPRSA-N 0.000 description 6
• QOJDBRUCOXQSSK-AJNGGQMLSA-N Lys-Ile-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(O)=O QOJDBRUCOXQSSK-AJNGGQMLSA-N 0.000 description 6
• UQJOKDAYFULYIX-AVGNSLFASA-N Lys-Pro-Pro Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 UQJOKDAYFULYIX-AVGNSLFASA-N 0.000 description 6
• 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 6
• SLQDSYZHHOKQSR-QXEWZRGKSA-N Met-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCSC SLQDSYZHHOKQSR-QXEWZRGKSA-N 0.000 description 6
• 241001529936 Murinae Species 0.000 description 6
• 241000699666 Mus <mouse, genus> Species 0.000 description 6
• MHNBYYFXWDUGBW-RPTUDFQQSA-N Phe-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CC=CC=C2)N)O MHNBYYFXWDUGBW-RPTUDFQQSA-N 0.000 description 6
• QXNSKJLSLYCTMT-FXQIFTODSA-N Pro-Cys-Asp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O QXNSKJLSLYCTMT-FXQIFTODSA-N 0.000 description 6
• 238000012300 Sequence Analysis Methods 0.000 description 6
• QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 6
• AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 6
• RVGVIWNHABGIFH-IHRRRGAJSA-N Tyr-Val-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O RVGVIWNHABGIFH-IHRRRGAJSA-N 0.000 description 6
• DLYOEFGPYTZVSP-AEJSXWLSSA-N Val-Cys-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N DLYOEFGPYTZVSP-AEJSXWLSSA-N 0.000 description 6
• 238000007792 addition Methods 0.000 description 6
• 108010086434 alanyl-seryl-glycine Proteins 0.000 description 6
• 108010068265 aspartyltyrosine Proteins 0.000 description 6
• 210000002798 bone marrow cell Anatomy 0.000 description 6
• 238000004113 cell culture Methods 0.000 description 6
• 210000004443 dendritic cell Anatomy 0.000 description 6
• 238000001514 detection method Methods 0.000 description 6
• 239000013604 expression vector Substances 0.000 description 6
• 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 6
• 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 6
• 108010009298 lysylglutamic acid Proteins 0.000 description 6
• 210000002540 macrophage Anatomy 0.000 description 6
• 210000001616 monocyte Anatomy 0.000 description 6
• 230000001582 osteoblastic effect Effects 0.000 description 6
• 238000002823 phage display Methods 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 239000000758 substrate Substances 0.000 description 6
• 108010071097 threonyl-lysyl-proline Proteins 0.000 description 6
• OMMDTNGURYRDAC-NRPADANISA-N Ala-Glu-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OMMDTNGURYRDAC-NRPADANISA-N 0.000 description 5
• OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 5
• NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 5
• YEBZNKPPOHFZJM-BPNCWPANSA-N Ala-Tyr-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O YEBZNKPPOHFZJM-BPNCWPANSA-N 0.000 description 5
• ZAESWDKAMDVHLL-RCOVLWMOSA-N Asn-Val-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O ZAESWDKAMDVHLL-RCOVLWMOSA-N 0.000 description 5
• DBWYWXNMZZYIRY-LPEHRKFASA-N Asp-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O DBWYWXNMZZYIRY-LPEHRKFASA-N 0.000 description 5
• WYOSXGYAKZQPGF-SRVKXCTJSA-N Asp-His-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC(=O)O)N WYOSXGYAKZQPGF-SRVKXCTJSA-N 0.000 description 5
• SCQIQCWLOMOEFP-DCAQKATOSA-N Asp-Leu-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O SCQIQCWLOMOEFP-DCAQKATOSA-N 0.000 description 5
• CLUMZOKVGUWUFD-CIUDSAMLSA-N Asp-Leu-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O CLUMZOKVGUWUFD-CIUDSAMLSA-N 0.000 description 5
• YWLDTBBUHZJQHW-KKUMJFAQSA-N Asp-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N YWLDTBBUHZJQHW-KKUMJFAQSA-N 0.000 description 5
• OQMGSMNZVHYDTQ-ZKWXMUAHSA-N Asp-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N OQMGSMNZVHYDTQ-ZKWXMUAHSA-N 0.000 description 5
• 108010006835 Atrial Natriuretic Factor Receptors Proteins 0.000 description 5
• GGRDJANMZPGMNS-CIUDSAMLSA-N Cys-Ser-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O GGRDJANMZPGMNS-CIUDSAMLSA-N 0.000 description 5
• DGQJGBDBFVGLGL-ZKWXMUAHSA-N Cys-Val-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N DGQJGBDBFVGLGL-ZKWXMUAHSA-N 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• 238000012286 ELISA Assay Methods 0.000 description 5
• ZGXGVBYEJGVJMV-HJGDQZAQSA-N Glu-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O ZGXGVBYEJGVJMV-HJGDQZAQSA-N 0.000 description 5
• SSFWXSNOKDZNHY-QXEWZRGKSA-N Gly-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN SSFWXSNOKDZNHY-QXEWZRGKSA-N 0.000 description 5
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
• JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 5
• WUEIUSDAECDLQO-NAKRPEOUSA-N Ile-Ala-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)O)N WUEIUSDAECDLQO-NAKRPEOUSA-N 0.000 description 5
• IITVUURPOYGCTD-NAKRPEOUSA-N Ile-Pro-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IITVUURPOYGCTD-NAKRPEOUSA-N 0.000 description 5
• NSPNUMNLZNOPAQ-SJWGOKEGSA-N Ile-Tyr-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N NSPNUMNLZNOPAQ-SJWGOKEGSA-N 0.000 description 5
• 108010065920 Insulin Lispro Proteins 0.000 description 5
• KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 5
• LJKJVTCIRDCITR-SRVKXCTJSA-N Leu-Cys-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N LJKJVTCIRDCITR-SRVKXCTJSA-N 0.000 description 5
• IWTBYNQNAPECCS-AVGNSLFASA-N Leu-Glu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IWTBYNQNAPECCS-AVGNSLFASA-N 0.000 description 5
• DCGXHWINSHEPIR-SRVKXCTJSA-N Leu-Lys-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N DCGXHWINSHEPIR-SRVKXCTJSA-N 0.000 description 5
• BGZCJDGBBUUBHA-KKUMJFAQSA-N Leu-Lys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O BGZCJDGBBUUBHA-KKUMJFAQSA-N 0.000 description 5
• ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 5
• WVJNGSFKBKOKRV-AJNGGQMLSA-N Lys-Leu-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WVJNGSFKBKOKRV-AJNGGQMLSA-N 0.000 description 5
• WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 5
• YXPJCVNIDDKGOE-MELADBBJSA-N Lys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N)C(=O)O YXPJCVNIDDKGOE-MELADBBJSA-N 0.000 description 5
• QAVZUKIPOMBLMC-AVGNSLFASA-N Met-Val-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(C)C QAVZUKIPOMBLMC-AVGNSLFASA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 241000283973 Oryctolagus cuniculus Species 0.000 description 5
• 208000010191 Osteitis Deformans Diseases 0.000 description 5
• 208000027868 Paget disease Diseases 0.000 description 5
• QMMRHASQEVCJGR-UBHSHLNASA-N Phe-Ala-Pro Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=CC=C1 QMMRHASQEVCJGR-UBHSHLNASA-N 0.000 description 5
• IWZRODDWOSIXPZ-IRXDYDNUSA-N Phe-Phe-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(O)=O)C1=CC=CC=C1 IWZRODDWOSIXPZ-IRXDYDNUSA-N 0.000 description 5
• IPVPGAADZXRZSH-RNXOBYDBSA-N Phe-Tyr-Trp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O IPVPGAADZXRZSH-RNXOBYDBSA-N 0.000 description 5
• AMBLXEMWFARNNQ-DCAQKATOSA-N Pro-Asn-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@@H]1CCCN1 AMBLXEMWFARNNQ-DCAQKATOSA-N 0.000 description 5
• 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 5
• PTLOFJZJADCNCD-DCAQKATOSA-N Pro-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 PTLOFJZJADCNCD-DCAQKATOSA-N 0.000 description 5
• HBZBPFLJNDXRAY-FXQIFTODSA-N Ser-Ala-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O HBZBPFLJNDXRAY-FXQIFTODSA-N 0.000 description 5
• 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 5
• 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 5
• 101710097160 Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 5
• ZOBLBMGJKVJVEV-BZSNNMDCSA-N Tyr-Lys-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O ZOBLBMGJKVJVEV-BZSNNMDCSA-N 0.000 description 5
• LHADRQBREKTRLR-DCAQKATOSA-N Val-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N LHADRQBREKTRLR-DCAQKATOSA-N 0.000 description 5
• HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 5
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
• 238000001042 affinity chromatography Methods 0.000 description 5
• 108010041407 alanylaspartic acid Proteins 0.000 description 5
• 238000004166 bioassay Methods 0.000 description 5
• 238000003776 cleavage reaction Methods 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 108010060199 cysteinylproline Proteins 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 230000018109 developmental process Effects 0.000 description 5
• 108010054813 diprotin B Proteins 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 231100000673 dose–response relationship Toxicity 0.000 description 5
• 108010059898 glycyl-tyrosyl-lysine Proteins 0.000 description 5
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
• 210000000987 immune system Anatomy 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 229910052500 inorganic mineral Inorganic materials 0.000 description 5
• 238000000111 isothermal titration calorimetry Methods 0.000 description 5
• 210000003734 kidney Anatomy 0.000 description 5
• 108010044056 leucyl-phenylalanine Proteins 0.000 description 5
• 108010057821 leucylproline Proteins 0.000 description 5
• 108010003700 lysyl aspartic acid Proteins 0.000 description 5
• 108010054155 lysyllysine Proteins 0.000 description 5
• 208000027202 mammary Paget disease Diseases 0.000 description 5
• 239000003550 marker Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 239000011707 mineral Substances 0.000 description 5
• 201000001245 periodontitis Diseases 0.000 description 5
• 108010084525 phenylalanyl-phenylalanyl-glycine Proteins 0.000 description 5
• 108010090894 prolylleucine Proteins 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 230000007017 scission Effects 0.000 description 5
• 108010080629 tryptophan-leucine Proteins 0.000 description 5
• 108010084932 tryptophyl-proline Proteins 0.000 description 5
• WQVYAWIMAWTGMW-ZLUOBGJFSA-N Ala-Asp-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N WQVYAWIMAWTGMW-ZLUOBGJFSA-N 0.000 description 4
• IYKVSFNGSWTTNZ-GUBZILKMSA-N Ala-Val-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IYKVSFNGSWTTNZ-GUBZILKMSA-N 0.000 description 4
• PAPSMOYMQDWIOR-AVGNSLFASA-N Arg-Lys-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PAPSMOYMQDWIOR-AVGNSLFASA-N 0.000 description 4
• 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 4
• QEQVUHQQYDZUEN-GUBZILKMSA-N Asn-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N QEQVUHQQYDZUEN-GUBZILKMSA-N 0.000 description 4
• FBODFHMLALOPHP-GUBZILKMSA-N Asn-Lys-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O FBODFHMLALOPHP-GUBZILKMSA-N 0.000 description 4
• 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 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
• FIAKNCXQFFKSSI-ZLUOBGJFSA-N Asp-Ser-Cys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O FIAKNCXQFFKSSI-ZLUOBGJFSA-N 0.000 description 4
• 206010065687 Bone loss Diseases 0.000 description 4
• 206010008723 Chondrodystrophy Diseases 0.000 description 4
• BNRHLRWCERLRTQ-BPUTZDHNSA-N Cys-Arg-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N BNRHLRWCERLRTQ-BPUTZDHNSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• MXOODARRORARSU-ACZMJKKPSA-N Glu-Ala-Ser Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N MXOODARRORARSU-ACZMJKKPSA-N 0.000 description 4
• NNQDRRUXFJYCCJ-NHCYSSNCSA-N Glu-Pro-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O NNQDRRUXFJYCCJ-NHCYSSNCSA-N 0.000 description 4
• MHHUEAIBJZWDBH-YUMQZZPRSA-N Gly-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN MHHUEAIBJZWDBH-YUMQZZPRSA-N 0.000 description 4
• 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 4
• MVZASEMJYJPJSI-IHPCNDPISA-N His-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC3=CN=CN3)N MVZASEMJYJPJSI-IHPCNDPISA-N 0.000 description 4
• SVVULKPWDBIPCO-BZSNNMDCSA-N His-Phe-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O SVVULKPWDBIPCO-BZSNNMDCSA-N 0.000 description 4
• 206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 4
• 201000002980 Hyperparathyroidism Diseases 0.000 description 4
• FJWALBCCVIHZBS-QXEWZRGKSA-N Ile-Met-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)O)N FJWALBCCVIHZBS-QXEWZRGKSA-N 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• 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 4
• KWURTLAFFDOTEQ-GUBZILKMSA-N Leu-Cys-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KWURTLAFFDOTEQ-GUBZILKMSA-N 0.000 description 4
• IAJFFZORSWOZPQ-SRVKXCTJSA-N Leu-Leu-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IAJFFZORSWOZPQ-SRVKXCTJSA-N 0.000 description 4
• ADJWHHZETYAAAX-SRVKXCTJSA-N Leu-Ser-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ADJWHHZETYAAAX-SRVKXCTJSA-N 0.000 description 4
• JGKHAFUAPZCCDU-BZSNNMDCSA-N Leu-Tyr-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CC=C(O)C=C1 JGKHAFUAPZCCDU-BZSNNMDCSA-N 0.000 description 4
• WLCYCADOWRMSAJ-CIUDSAMLSA-N Lys-Asn-Cys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(O)=O WLCYCADOWRMSAJ-CIUDSAMLSA-N 0.000 description 4
• HQVDJTYKCMIWJP-YUMQZZPRSA-N Lys-Asn-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O HQVDJTYKCMIWJP-YUMQZZPRSA-N 0.000 description 4
• WAIHHELKYSFIQN-XUXIUFHCSA-N Lys-Ile-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O WAIHHELKYSFIQN-XUXIUFHCSA-N 0.000 description 4
• LJADEBULDNKJNK-IHRRRGAJSA-N Lys-Leu-Val Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LJADEBULDNKJNK-IHRRRGAJSA-N 0.000 description 4
• MTBLFIQZECOEBY-IHRRRGAJSA-N Lys-Met-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(O)=O MTBLFIQZECOEBY-IHRRRGAJSA-N 0.000 description 4
• 206010027452 Metastases to bone Diseases 0.000 description 4
• XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 4
• 102000005951 Netrin Receptors Human genes 0.000 description 4
• 108010030865 Netrin Receptors Proteins 0.000 description 4
• 102100029514 Netrin receptor UNC5C Human genes 0.000 description 4
• 206010031240 Osteodystrophy Diseases 0.000 description 4
• 108010067902 Peptide Library Proteins 0.000 description 4
• RMKGXGPQIPLTFC-KKUMJFAQSA-N Phe-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RMKGXGPQIPLTFC-KKUMJFAQSA-N 0.000 description 4
• FUAIIFPQELBNJF-ULQDDVLXSA-N Phe-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N FUAIIFPQELBNJF-ULQDDVLXSA-N 0.000 description 4
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 4
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 4
• OGRYXQOUFHAMPI-DCAQKATOSA-N Pro-Cys-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O OGRYXQOUFHAMPI-DCAQKATOSA-N 0.000 description 4
• DWGFLKQSGRUQTI-IHRRRGAJSA-N Pro-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 DWGFLKQSGRUQTI-IHRRRGAJSA-N 0.000 description 4
• 102100030054 Secreted frizzled-related protein 2 Human genes 0.000 description 4
• PXQUBKWZENPDGE-CIQUZCHMSA-N Thr-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)N PXQUBKWZENPDGE-CIQUZCHMSA-N 0.000 description 4
• MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 description 4
• PALLCTDPFINNMM-JQHSSLGASA-N Trp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N PALLCTDPFINNMM-JQHSSLGASA-N 0.000 description 4
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 4
• KHCSOLAHNLOXJR-BZSNNMDCSA-N Tyr-Leu-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHCSOLAHNLOXJR-BZSNNMDCSA-N 0.000 description 4
• 101150065336 Unc5c gene Proteins 0.000 description 4
• 208000008919 achondroplasia Diseases 0.000 description 4
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 230000003321 amplification Effects 0.000 description 4
• 239000000427 antigen Substances 0.000 description 4
• 102000036639 antigens Human genes 0.000 description 4
• 108091007433 antigens Proteins 0.000 description 4
• 230000006907 apoptotic process Effects 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 230000036755 cellular response Effects 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 230000002708 enhancing effect Effects 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 108010089804 glycyl-threonine Proteins 0.000 description 4
• 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 4
• 230000028993 immune response Effects 0.000 description 4
• 238000011534 incubation Methods 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• 230000002101 lytic effect Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 238000003199 nucleic acid amplification method Methods 0.000 description 4
• 230000011164 ossification Effects 0.000 description 4
• 238000004091 panning Methods 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 239000008194 pharmaceutical composition Substances 0.000 description 4
• 239000013641 positive control Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 238000012545 processing Methods 0.000 description 4
• 238000000159 protein binding assay Methods 0.000 description 4
• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 4
• 238000012340 reverse transcriptase PCR Methods 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 230000004936 stimulating effect Effects 0.000 description 4
• 230000000638 stimulation Effects 0.000 description 4
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 4
• 229960005486 vaccine Drugs 0.000 description 4
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
• RDIKFPRVLJLMER-BQBZGAKWSA-N Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)N RDIKFPRVLJLMER-BQBZGAKWSA-N 0.000 description 3
• 108010001789 Calcitonin Receptors Proteins 0.000 description 3
• 102100038520 Calcitonin receptor Human genes 0.000 description 3
• 101710132601 Capsid protein Proteins 0.000 description 3
• 101710094648 Coat protein Proteins 0.000 description 3
• 108091026890 Coding region Proteins 0.000 description 3
• TXGDWPBLUFQODU-XGEHTFHBSA-N Cys-Pro-Thr Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O TXGDWPBLUFQODU-XGEHTFHBSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 208000010412 Glaucoma Diseases 0.000 description 3
• 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 3
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
• 101000830603 Homo sapiens Tumor necrosis factor ligand superfamily member 11 Proteins 0.000 description 3
• 108060003951 Immunoglobulin Proteins 0.000 description 3
• 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 3
• 101710125418 Major capsid protein Proteins 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• 108091005461 Nucleic proteins Proteins 0.000 description 3
• 101710141454 Nucleoprotein Proteins 0.000 description 3
• 108010035042 Osteoprotegerin Proteins 0.000 description 3
• 102000008108 Osteoprotegerin Human genes 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• 108091005804 Peptidases Proteins 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 101710083689 Probable capsid protein Proteins 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 238000010240 RT-PCR analysis Methods 0.000 description 3
• 108050007987 Secreted frizzled-related protein 2 Proteins 0.000 description 3
• HNDMFDBQXYZSRM-IHRRRGAJSA-N Ser-Val-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HNDMFDBQXYZSRM-IHRRRGAJSA-N 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000000556 agonist Substances 0.000 description 3
• 235000004279 alanine Nutrition 0.000 description 3
• 238000012867 alanine scanning Methods 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 210000001185 bone marrow Anatomy 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 3
• 238000010586 diagram Methods 0.000 description 3
• 230000029087 digestion Effects 0.000 description 3
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
• 239000005090 green fluorescent protein Substances 0.000 description 3
• 102000053529 human TNFSF11 Human genes 0.000 description 3
• 102000018358 immunoglobulin Human genes 0.000 description 3
• 238000007901 in situ hybridization Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 208000001685 postmenopausal osteoporosis Diseases 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 238000012163 sequencing technique Methods 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 238000010186 staining Methods 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
• JVJUWEFOGFCHKR-UHFFFAOYSA-N 2-(diethylamino)ethyl 1-(3,4-dimethylphenyl)cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C(C)C(C)=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 JVJUWEFOGFCHKR-UHFFFAOYSA-N 0.000 description 2
• PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 2
• HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
• SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 2
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 229920000856 Amylose Polymers 0.000 description 2
• 108010046080 CD27 Ligand Proteins 0.000 description 2
• 102100025221 CD70 antigen Human genes 0.000 description 2
• 108020004635 Complementary DNA Proteins 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 2
• SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
• 108010039471 Fas Ligand Protein Proteins 0.000 description 2
• JXFLPKSDLDEOQK-JHEQGTHGSA-N Gln-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O JXFLPKSDLDEOQK-JHEQGTHGSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• 101710154606 Hemagglutinin Proteins 0.000 description 2
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
• 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 2
• 206010061598 Immunodeficiency Diseases 0.000 description 2
• 208000029462 Immunodeficiency disease Diseases 0.000 description 2
• 108090001005 Interleukin-6 Proteins 0.000 description 2
• 102000004889 Interleukin-6 Human genes 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 108020001621 Natriuretic Peptide Proteins 0.000 description 2
• 102000004571 Natriuretic peptide Human genes 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 108010063605 Netrins Proteins 0.000 description 2
• 102000010803 Netrins Human genes 0.000 description 2
• 239000004677 Nylon Substances 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 208000003076 Osteolysis Diseases 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
• 101710176177 Protein A56 Proteins 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 101150109894 TGFA gene Proteins 0.000 description 2
• 206010052779 Transplant rejections Diseases 0.000 description 2
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 2
• 102100032236 Tumor necrosis factor receptor superfamily member 11B Human genes 0.000 description 2
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• 230000001464 adherent effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• INJRKJPEYSAMPD-UHFFFAOYSA-N aluminum;silicic acid;hydrate Chemical compound O.[Al].[Al].O[Si](O)(O)O INJRKJPEYSAMPD-UHFFFAOYSA-N 0.000 description 2
• 238000000137 annealing Methods 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000030741 antigen processing and presentation Effects 0.000 description 2
• 108010047857 aspartylglycine Proteins 0.000 description 2
• 239000003855 balanced salt solution Substances 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 230000014461 bone development Effects 0.000 description 2
• 239000002775 capsule Substances 0.000 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 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 239000003636 conditioned culture medium Substances 0.000 description 2
• 230000002596 correlated effect Effects 0.000 description 2
• ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
• 210000004748 cultured cell Anatomy 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 230000003412 degenerative effect Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 239000010432 diamond Substances 0.000 description 2
• QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
• SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 238000009510 drug design Methods 0.000 description 2
• 210000002257 embryonic structure Anatomy 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
• IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 2
• 229940011871 estrogen Drugs 0.000 description 2
• 239000000262 estrogen Substances 0.000 description 2
• VYXSBFYARXAAKO-UHFFFAOYSA-N ethyl 2-[3-(ethylamino)-6-ethylimino-2,7-dimethylxanthen-9-yl]benzoate;hydron;chloride Chemical compound [Cl-].C1=2C=C(C)C(NCC)=CC=2OC2=CC(=[NH+]CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-UHFFFAOYSA-N 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 2
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 238000010353 genetic engineering Methods 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 210000004349 growth plate Anatomy 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 239000000185 hemagglutinin Substances 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 230000013632 homeostatic process Effects 0.000 description 2
• 230000003054 hormonal effect Effects 0.000 description 2
• 230000000121 hypercalcemic effect Effects 0.000 description 2
• 238000003119 immunoblot Methods 0.000 description 2
• 230000007813 immunodeficiency Effects 0.000 description 2
• 238000010820 immunofluorescence microscopy Methods 0.000 description 2
• 238000001114 immunoprecipitation Methods 0.000 description 2
• 230000001506 immunosuppresive effect Effects 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 210000004969 inflammatory cell Anatomy 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 208000029791 lytic metastatic bone lesion Diseases 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000035800 maturation Effects 0.000 description 2
• 230000009245 menopause Effects 0.000 description 2
• 230000003278 mimic effect Effects 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 210000005087 mononuclear cell Anatomy 0.000 description 2
• 239000000692 natriuretic peptide Substances 0.000 description 2
• 230000006654 negative regulation of apoptotic process Effects 0.000 description 2
• 229920001778 nylon Polymers 0.000 description 2
• 210000003463 organelle Anatomy 0.000 description 2
• 230000002177 osteoclastogenic effect Effects 0.000 description 2
• 230000003642 osteotropic effect Effects 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 238000012261 overproduction Methods 0.000 description 2
• 239000006179 pH buffering agent Substances 0.000 description 2
• 230000008506 pathogenesis Effects 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 239000002504 physiological saline solution Substances 0.000 description 2
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
• 108091033319 polynucleotide Proteins 0.000 description 2
• 102000040430 polynucleotide Human genes 0.000 description 2
• 239000002157 polynucleotide Substances 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 238000003259 recombinant expression Methods 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 238000013391 scatchard analysis Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 229940035044 sorbitan monolaurate Drugs 0.000 description 2
• 230000003393 splenic effect Effects 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 210000002536 stromal cell Anatomy 0.000 description 2
• 239000013589 supplement Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 230000003827 upregulation Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
• 238000009736 wetting Methods 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 1
• ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
• DUFUXAHBRPMOFG-UHFFFAOYSA-N 1-(4-anilinonaphthalen-1-yl)pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C1=CC=CC=C11)=CC=C1NC1=CC=CC=C1 DUFUXAHBRPMOFG-UHFFFAOYSA-N 0.000 description 1
• ZTTARJIAPRWUHH-UHFFFAOYSA-N 1-isothiocyanatoacridine Chemical compound C1=CC=C2C=C3C(N=C=S)=CC=CC3=NC2=C1 ZTTARJIAPRWUHH-UHFFFAOYSA-N 0.000 description 1
• OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
• VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
• RUDINRUXCKIXAJ-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,14-heptacosafluorotetradecanoic acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F RUDINRUXCKIXAJ-UHFFFAOYSA-N 0.000 description 1
• DLZKEQQWXODGGZ-KCJUWKMLSA-N 2-[[(2r)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DLZKEQQWXODGGZ-KCJUWKMLSA-N 0.000 description 1
• SNBCLPGEMZEWLU-QXFUBDJGSA-N 2-chloro-n-[[(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]acetamide Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CNC(=O)CCl)[C@@H](O)C1 SNBCLPGEMZEWLU-QXFUBDJGSA-N 0.000 description 1
• CPBJMKMKNCRKQB-UHFFFAOYSA-N 3,3-bis(4-hydroxy-3-methylphenyl)-2-benzofuran-1-one Chemical compound C1=C(O)C(C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C=C(C)C(O)=CC=2)=C1 CPBJMKMKNCRKQB-UHFFFAOYSA-N 0.000 description 1
• GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
• SMBSZJBWYCGCJP-UHFFFAOYSA-N 3-(diethylamino)chromen-2-one Chemical compound C1=CC=C2OC(=O)C(N(CC)CC)=CC2=C1 SMBSZJBWYCGCJP-UHFFFAOYSA-N 0.000 description 1
• YSCNMFDFYJUPEF-OWOJBTEDSA-N 4,4'-diisothiocyano-trans-stilbene-2,2'-disulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=C=S)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S(O)(=O)=O YSCNMFDFYJUPEF-OWOJBTEDSA-N 0.000 description 1
• YJCCSLGGODRWKK-NSCUHMNNSA-N 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid Chemical compound OS(=O)(=O)C1=CC(NC(=O)C)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S(O)(=O)=O YJCCSLGGODRWKK-NSCUHMNNSA-N 0.000 description 1
• OSWZKAVBSQAVFI-UHFFFAOYSA-N 4-[(4-isothiocyanatophenyl)diazenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(N=C=S)C=C1 OSWZKAVBSQAVFI-UHFFFAOYSA-N 0.000 description 1
• WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 1
• ZWONWYNZSWOYQC-UHFFFAOYSA-N 5-benzamido-3-[[5-[[4-chloro-6-(4-sulfoanilino)-1,3,5-triazin-2-yl]amino]-2-sulfophenyl]diazenyl]-4-hydroxynaphthalene-2,7-disulfonic acid Chemical compound OC1=C(N=NC2=CC(NC3=NC(NC4=CC=C(C=C4)S(O)(=O)=O)=NC(Cl)=N3)=CC=C2S(O)(=O)=O)C(=CC2=C1C(NC(=O)C1=CC=CC=C1)=CC(=C2)S(O)(=O)=O)S(O)(=O)=O ZWONWYNZSWOYQC-UHFFFAOYSA-N 0.000 description 1
• NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
• AXGKYURDYTXCAG-UHFFFAOYSA-N 5-isothiocyanato-2-[2-(4-isothiocyanato-2-sulfophenyl)ethyl]benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=C=S)=CC=C1CCC1=CC=C(N=C=S)C=C1S(O)(=O)=O AXGKYURDYTXCAG-UHFFFAOYSA-N 0.000 description 1
• HWQQCFPHXPNXHC-UHFFFAOYSA-N 6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=CC=2)OC(=O)C1=CC=2NC1=NC(Cl)=NC(Cl)=N1 HWQQCFPHXPNXHC-UHFFFAOYSA-N 0.000 description 1
• TXSWURLNYUQATR-UHFFFAOYSA-N 6-amino-2-(3-ethenylsulfonylphenyl)-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1C1=CC=CC(S(=O)(=O)C=C)=C1 TXSWURLNYUQATR-UHFFFAOYSA-N 0.000 description 1
• WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 1
• SGAOZXGJGQEBHA-UHFFFAOYSA-N 82344-98-7 Chemical compound C1CCN2CCCC(C=C3C4(OC(C5=CC(=CC=C54)N=C=S)=O)C4=C5)=C2C1=C3OC4=C1CCCN2CCCC5=C12 SGAOZXGJGQEBHA-UHFFFAOYSA-N 0.000 description 1
• GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
• SUMYEVXWCAYLLJ-GUBZILKMSA-N Ala-Leu-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O SUMYEVXWCAYLLJ-GUBZILKMSA-N 0.000 description 1
• GFEDXKNBZMPEDM-KZVJFYERSA-N Ala-Met-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFEDXKNBZMPEDM-KZVJFYERSA-N 0.000 description 1
• FVNAUOZKIPAYNA-BPNCWPANSA-N Ala-Met-Tyr Chemical compound CSCC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FVNAUOZKIPAYNA-BPNCWPANSA-N 0.000 description 1
• MMLHRUJLOUSRJX-CIUDSAMLSA-N Ala-Ser-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN MMLHRUJLOUSRJX-CIUDSAMLSA-N 0.000 description 1
• LSMDIAAALJJLRO-XQXXSGGOSA-N Ala-Thr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O LSMDIAAALJJLRO-XQXXSGGOSA-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
• YXXPVUOMPSZURS-ZLIFDBKOSA-N Ala-Trp-Leu Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](C)N)=CNC2=C1 YXXPVUOMPSZURS-ZLIFDBKOSA-N 0.000 description 1
• 108010032595 Antibody Binding Sites Proteins 0.000 description 1
• SLQQPJBDBVPVQV-JYJNAYRXSA-N Arg-Phe-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O SLQQPJBDBVPVQV-JYJNAYRXSA-N 0.000 description 1
• DRDWXKWUSIKKOB-PJODQICGSA-N Arg-Trp-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O DRDWXKWUSIKKOB-PJODQICGSA-N 0.000 description 1
• XMGVWQWEWWULNS-BPUTZDHNSA-N Arg-Trp-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N XMGVWQWEWWULNS-BPUTZDHNSA-N 0.000 description 1
• ZCSHHTFOZULVLN-SZMVWBNQSA-N Arg-Trp-Val Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N)=CNC2=C1 ZCSHHTFOZULVLN-SZMVWBNQSA-N 0.000 description 1
• KGCUOPPQTPZILL-CIUDSAMLSA-N Asn-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N KGCUOPPQTPZILL-CIUDSAMLSA-N 0.000 description 1
• IICZCLFBILYRCU-WHFBIAKZSA-N Asn-Gly-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IICZCLFBILYRCU-WHFBIAKZSA-N 0.000 description 1
• YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 1
• 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
• 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
• 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 102100021277 Beta-secretase 2 Human genes 0.000 description 1
• 101710150190 Beta-secretase 2 Proteins 0.000 description 1
• 101000864740 Bos taurus Secreted frizzled-related protein 1 Proteins 0.000 description 1
• 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
• 206010006895 Cachexia Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 102000003952 Caspase 3 Human genes 0.000 description 1
• 108090000397 Caspase 3 Proteins 0.000 description 1
• 101000741396 Chlamydia muridarum (strain MoPn / Nigg) Probable oxidoreductase TC_0900 Proteins 0.000 description 1
• 101000741399 Chlamydia pneumoniae Probable oxidoreductase CPn_0761/CP_1111/CPj0761/CpB0789 Proteins 0.000 description 1
• 101000741400 Chlamydia trachomatis (strain D/UW-3/Cx) Probable oxidoreductase CT_610 Proteins 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• VPAXJOUATWLOPR-UHFFFAOYSA-N Conferone Chemical compound C1=CC(=O)OC2=CC(OCC3C4(C)CCC(=O)C(C)(C)C4CC=C3C)=CC=C21 VPAXJOUATWLOPR-UHFFFAOYSA-N 0.000 description 1
• YUZPQIQWXLRFBW-ACZMJKKPSA-N Cys-Glu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O YUZPQIQWXLRFBW-ACZMJKKPSA-N 0.000 description 1
• LYSHSHHDBVKJRN-JBDRJPRFSA-N Cys-Ile-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CS)N LYSHSHHDBVKJRN-JBDRJPRFSA-N 0.000 description 1
• XZKJEOMFLDVXJG-KATARQTJSA-N Cys-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)N)O XZKJEOMFLDVXJG-KATARQTJSA-N 0.000 description 1
• XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
• 101100044298 Drosophila melanogaster fand gene Proteins 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 241001524679 Escherichia virus M13 Species 0.000 description 1
• QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 1
• 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
• 101150064015 FAS gene Proteins 0.000 description 1
• 108010074860 Factor Xa Proteins 0.000 description 1
• 108010057784 Fusion Regulatory Protein-1 Proteins 0.000 description 1
• 101150066516 GST gene Proteins 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• XXLBHPPXDUWYAG-XQXXSGGOSA-N Gln-Ala-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XXLBHPPXDUWYAG-XQXXSGGOSA-N 0.000 description 1
• ARPVSMCNIDAQBO-YUMQZZPRSA-N Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ARPVSMCNIDAQBO-YUMQZZPRSA-N 0.000 description 1
• VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 1
• CLODWIOAKCSBAN-BQBZGAKWSA-N Gly-Arg-Asp Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O CLODWIOAKCSBAN-BQBZGAKWSA-N 0.000 description 1
• XZRZILPOZBVTDB-GJZGRUSLSA-N Gly-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)CN)C(O)=O)=CNC2=C1 XZRZILPOZBVTDB-GJZGRUSLSA-N 0.000 description 1
• ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
• IMRNSEPSPFQNHF-STQMWFEESA-N Gly-Ser-Trp Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)O IMRNSEPSPFQNHF-STQMWFEESA-N 0.000 description 1
• FFJQHWKSGAWSTJ-BFHQHQDPSA-N Gly-Thr-Ala Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O FFJQHWKSGAWSTJ-BFHQHQDPSA-N 0.000 description 1
• 101100175482 Glycine max CG-3 gene Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 1
• 101500027325 Homo sapiens Atrial natriuretic peptide Proteins 0.000 description 1
• 101000864788 Homo sapiens Secreted frizzled-related protein 3 Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• 208000037147 Hypercalcaemia Diseases 0.000 description 1
• 208000013038 Hypocalcemia Diseases 0.000 description 1
• 206010061217 Infestation Diseases 0.000 description 1
• 108010041357 Integrin alpha3 Proteins 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• POJPZSMTTMLSTG-SRVKXCTJSA-N Leu-Asn-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N POJPZSMTTMLSTG-SRVKXCTJSA-N 0.000 description 1
• 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 1
• FKQPWMZLIIATBA-AJNGGQMLSA-N Leu-Lys-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FKQPWMZLIIATBA-AJNGGQMLSA-N 0.000 description 1
• 239000006137 Luria-Bertani broth Substances 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• 102100026238 Lymphotoxin-alpha Human genes 0.000 description 1
• GAHJXEMYXKLZRQ-AJNGGQMLSA-N Lys-Lys-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O GAHJXEMYXKLZRQ-AJNGGQMLSA-N 0.000 description 1
• GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
• NDJSSFWDYDUQID-YTWAJWBKSA-N Met-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCSC)N)O NDJSSFWDYDUQID-YTWAJWBKSA-N 0.000 description 1
• 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
• 101000864785 Mus musculus Secreted frizzled-related protein 2 Proteins 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
• BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
• NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• IXQIUDNVFVTQLJ-UHFFFAOYSA-N Naphthofluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C(C=CC=1C3=CC=C(O)C=1)=C3OC1=C2C=CC2=CC(O)=CC=C21 IXQIUDNVFVTQLJ-UHFFFAOYSA-N 0.000 description 1
• 108010025020 Nerve Growth Factor Proteins 0.000 description 1
• 244000061176 Nicotiana tabacum Species 0.000 description 1
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
• 206010049088 Osteopenia Diseases 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 241000235648 Pichia Species 0.000 description 1
• 101100335198 Pneumocystis carinii fol1 gene Proteins 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• UVKNEILZSJMKSR-FXQIFTODSA-N Pro-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1 UVKNEILZSJMKSR-FXQIFTODSA-N 0.000 description 1
• GFHOSBYCLACKEK-GUBZILKMSA-N Pro-Pro-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O GFHOSBYCLACKEK-GUBZILKMSA-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
• XRGIDCGRSSWCKE-SRVKXCTJSA-N Pro-Val-Met Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O XRGIDCGRSSWCKE-SRVKXCTJSA-N 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 108010079005 RDV peptide Proteins 0.000 description 1
• 108010065868 RNA polymerase SP6 Proteins 0.000 description 1
• 230000010799 Receptor Interactions Effects 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• BFDMCHRDSYTOLE-UHFFFAOYSA-N SC#N.NC(N)=N.ClC(Cl)Cl.OC1=CC=CC=C1 Chemical compound SC#N.NC(N)=N.ClC(Cl)Cl.OC1=CC=CC=C1 BFDMCHRDSYTOLE-UHFFFAOYSA-N 0.000 description 1
• 108050007990 Secreted frizzled-related protein 3 Proteins 0.000 description 1
• 102100030052 Secreted frizzled-related protein 4 Human genes 0.000 description 1
• 108050008088 Secreted frizzled-related protein 4 Proteins 0.000 description 1
• 102100023744 Secreted frizzled-related protein 5 Human genes 0.000 description 1
• 108050008305 Secreted frizzled-related protein 5 Proteins 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• WTPKKLMBNBCCNL-ACZMJKKPSA-N Ser-Cys-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N WTPKKLMBNBCCNL-ACZMJKKPSA-N 0.000 description 1
• PTWIYDNFWPXQSD-GARJFASQSA-N Ser-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N)C(=O)O PTWIYDNFWPXQSD-GARJFASQSA-N 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 108090000054 Syndecan-2 Proteins 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 101710137500 T7 RNA polymerase Proteins 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• VGYBYGQXZJDZJU-XQXXSGGOSA-N Thr-Glu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VGYBYGQXZJDZJU-XQXXSGGOSA-N 0.000 description 1
• ODXKUIGEPAGKKV-KATARQTJSA-N Thr-Leu-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)O)N)O ODXKUIGEPAGKKV-KATARQTJSA-N 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• JWGRSJCYCXEIKH-QEJZJMRPSA-N Trp-Glu-Cys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N JWGRSJCYCXEIKH-QEJZJMRPSA-N 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 1
• 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 1
• 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
• 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 1
• 206010054094 Tumour necrosis Diseases 0.000 description 1
• VTFWAGGJDRSQFG-MELADBBJSA-N Tyr-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O VTFWAGGJDRSQFG-MELADBBJSA-N 0.000 description 1
• ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
• NMANTMWGQZASQN-QXEWZRGKSA-N Val-Arg-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N NMANTMWGQZASQN-QXEWZRGKSA-N 0.000 description 1
• ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 1
• RYQUMYBMOJYYDK-NHCYSSNCSA-N Val-Pro-Glu Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RYQUMYBMOJYYDK-NHCYSSNCSA-N 0.000 description 1
• NHXZRXLFOBFMDM-AVGNSLFASA-N Val-Pro-Leu Chemical group CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)C(C)C NHXZRXLFOBFMDM-AVGNSLFASA-N 0.000 description 1
• BGXVHVMJZCSOCA-AVGNSLFASA-N Val-Pro-Lys Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)O)N BGXVHVMJZCSOCA-AVGNSLFASA-N 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• IOMLBTHPCVDRHM-UHFFFAOYSA-N [3-[(2,4-dimethylphenyl)carbamoyl]naphthalen-2-yl] dihydrogen phosphate Chemical compound CC1=CC(C)=CC=C1NC(=O)C1=CC2=CC=CC=C2C=C1OP(O)(O)=O IOMLBTHPCVDRHM-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000008351 acetate buffer Substances 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
• 229960000723 ampicillin Drugs 0.000 description 1
• 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 210000002159 anterior chamber Anatomy 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 210000001742 aqueous humor Anatomy 0.000 description 1
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 108010092854 aspartyllysine Proteins 0.000 description 1
• 238000000376 autoradiography Methods 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 238000002869 basic local alignment search tool Methods 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 238000013357 binding ELISA Methods 0.000 description 1
• 102000023732 binding proteins Human genes 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000002449 bone cell Anatomy 0.000 description 1
• 230000037186 bone physiology Effects 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 230000004094 calcium homeostasis Effects 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 229950008486 carperitide Drugs 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 230000008568 cell cell communication Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 108091092328 cellular RNA Proteins 0.000 description 1
• 230000023715 cellular developmental process Effects 0.000 description 1
• 230000008614 cellular interaction Effects 0.000 description 1
• 238000009614 chemical analysis method Methods 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 238000011198 co-culture assay Methods 0.000 description 1
• 230000004186 co-expression Effects 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 238000012875 competitive assay Methods 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 238000005094 computer simulation Methods 0.000 description 1
• JECGPMYZUFFYJW-UHFFFAOYSA-N conferone Natural products CC1=CCC2C(C)(C)C(=O)CCC2(C)C1COc3cccc4C=CC(=O)Oc34 JECGPMYZUFFYJW-UHFFFAOYSA-N 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229960000956 coumarin Drugs 0.000 description 1
• 235000001671 coumarin Nutrition 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 230000003292 diminished effect Effects 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
• OOYIOIOOWUGAHD-UHFFFAOYSA-L disodium;2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Br)=C([O-])C(Br)=C1OC1=C(Br)C([O-])=C(Br)C=C21 OOYIOIOOWUGAHD-UHFFFAOYSA-L 0.000 description 1
• KPBGWWXVWRSIAY-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-6-isothiocyanato-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=C(N=C=S)C=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 KPBGWWXVWRSIAY-UHFFFAOYSA-L 0.000 description 1
• 108010007093 dispase Proteins 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• XHXYXYGSUXANME-UHFFFAOYSA-N eosin 5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC(Br)=C(O)C(Br)=C1OC1=C(Br)C(O)=C(Br)C=C21 XHXYXYGSUXANME-UHFFFAOYSA-N 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• 238000013401 experimental design Methods 0.000 description 1
• 238000010195 expression analysis Methods 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
• 238000010363 gene targeting Methods 0.000 description 1
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
• 108010040856 glutamyl-cysteinyl-alanine Proteins 0.000 description 1
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
• 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 108010038082 heparin proteoglycan Proteins 0.000 description 1
• 108010040030 histidinoalanine Proteins 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 108010028295 histidylhistidine Proteins 0.000 description 1
• 238000009396 hybridization Methods 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 230000000148 hypercalcaemia Effects 0.000 description 1
• 208000030915 hypercalcemia disease Diseases 0.000 description 1
• 210000003559 hypertrophic chondrocyte Anatomy 0.000 description 1
• 230000000705 hypocalcaemia Effects 0.000 description 1
• 230000001184 hypocalcaemic effect Effects 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 208000003669 immune deficiency disease Diseases 0.000 description 1
• 230000006028 immune-suppresssive effect Effects 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 229940088592 immunologic factor Drugs 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 230000004957 immunoregulator effect Effects 0.000 description 1
• 230000003308 immunostimulating effect Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
• 150000002540 isothiocyanates Chemical class 0.000 description 1
• 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 1
• 229940107698 malachite green Drugs 0.000 description 1
• 238000013227 male C57BL/6J mice Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• HNJJXZKZRAWDPF-UHFFFAOYSA-N methapyrilene Chemical group C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CS1 HNJJXZKZRAWDPF-UHFFFAOYSA-N 0.000 description 1
• 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 230000005305 organ development Effects 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000004409 osteocyte Anatomy 0.000 description 1
• AFAIELJLZYUNPW-UHFFFAOYSA-N pararosaniline free base Chemical compound C1=CC(N)=CC=C1C(C=1C=CC(N)=CC=1)=C1C=CC(=N)C=C1 AFAIELJLZYUNPW-UHFFFAOYSA-N 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 125000000405 phenylalanyl group Chemical group 0.000 description 1
• ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
• 230000008288 physiological mechanism Effects 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 230000004983 pleiotropic effect Effects 0.000 description 1
• 229920002401 polyacrylamide Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 230000008092 positive effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
• 108010077112 prolyl-proline Proteins 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• AJMSJNPWXJCWOK-UHFFFAOYSA-N pyren-1-yl butanoate Chemical compound C1=C2C(OC(=O)CCC)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 AJMSJNPWXJCWOK-UHFFFAOYSA-N 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000003014 reinforcing effect Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 230000028890 skeletal system morphogenesis Effects 0.000 description 1
• HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000001433 sodium tartrate Substances 0.000 description 1
• 229960002167 sodium tartrate Drugs 0.000 description 1
• 235000011004 sodium tartrates Nutrition 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 238000012916 structural analysis Methods 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• WGTODYJZXSJIAG-UHFFFAOYSA-N tetramethylrhodamine chloride Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C(O)=O WGTODYJZXSJIAG-UHFFFAOYSA-N 0.000 description 1
• MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 230000001256 tonic effect Effects 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000011820 transgenic animal model Methods 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 238000001419 two-dimensional polyacrylamide gel electrophoresis Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 238000010200 validation analysis Methods 0.000 description 1
• 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 150000003722 vitamin derivatives Chemical class 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1