CN113899908B - 磷酸化蛋白质在膜性肾病中的应用 - Google Patents
磷酸化蛋白质在膜性肾病中的应用 Download PDFInfo
- Publication number
- CN113899908B CN113899908B CN202111107560.3A CN202111107560A CN113899908B CN 113899908 B CN113899908 B CN 113899908B CN 202111107560 A CN202111107560 A CN 202111107560A CN 113899908 B CN113899908 B CN 113899908B
- Authority
- CN
- China
- Prior art keywords
- glu
- ezr
- site
- imn
- lys
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 201000008350 membranous glomerulonephritis Diseases 0.000 title claims abstract description 27
- 206010018372 Glomerulonephritis membranous Diseases 0.000 title abstract description 22
- 231100000855 membranous nephropathy Toxicity 0.000 title abstract description 22
- 108091005981 phosphorylated proteins Proteins 0.000 title description 12
- 230000026731 phosphorylation Effects 0.000 claims abstract description 43
- 238000006366 phosphorylation reaction Methods 0.000 claims abstract description 43
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 11
- 210000005084 renal tissue Anatomy 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 210000000557 podocyte Anatomy 0.000 abstract description 17
- 210000004027 cell Anatomy 0.000 abstract description 9
- 230000006378 damage Effects 0.000 abstract description 8
- 238000011862 kidney biopsy Methods 0.000 abstract description 8
- 208000027418 Wounds and injury Diseases 0.000 abstract description 7
- 208000014674 injury Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 230000003828 downregulation Effects 0.000 abstract description 6
- 230000007423 decrease Effects 0.000 abstract description 4
- 206010061818 Disease progression Diseases 0.000 abstract description 3
- 230000003247 decreasing effect Effects 0.000 abstract description 3
- 230000005750 disease progression Effects 0.000 abstract description 3
- 238000011532 immunohistochemical staining Methods 0.000 abstract description 3
- 102100020903 Ezrin Human genes 0.000 description 35
- 108090000623 proteins and genes Proteins 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 13
- 230000037361 pathway Effects 0.000 description 10
- 239000003814 drug Substances 0.000 description 9
- 230000002055 immunohistochemical effect Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 108091005573 modified proteins Proteins 0.000 description 7
- 102000035118 modified proteins Human genes 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 230000005012 migration Effects 0.000 description 6
- 238000013508 migration Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- 102100030571 STE20-like serine/threonine-protein kinase Human genes 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 210000001282 glomerular podocyte Anatomy 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 201000001474 proteinuria Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001578 tight junction Anatomy 0.000 description 4
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 3
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 3
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 3
- 108010044940 alanylglutamine Proteins 0.000 description 3
- 108010008355 arginyl-glutamine Proteins 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000024924 glomerular filtration Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000006916 protein interaction Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 102100030374 Actin, cytoplasmic 2 Human genes 0.000 description 2
- HJVGMOYJDDXLMI-AVGNSLFASA-N Arg-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCCNC(N)=N HJVGMOYJDDXLMI-AVGNSLFASA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108091008875 B cell receptors Proteins 0.000 description 2
- 102100028906 Catenin delta-1 Human genes 0.000 description 2
- 102000010970 Connexin Human genes 0.000 description 2
- 108050001175 Connexin Proteins 0.000 description 2
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 2
- 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 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101710157230 STE20-like serine/threonine-protein kinase Proteins 0.000 description 2
- GYDFRTRSSXOZCR-ACZMJKKPSA-N Ser-Ser-Glu Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GYDFRTRSSXOZCR-ACZMJKKPSA-N 0.000 description 2
- 101710183953 Serine/threonine-protein kinase 25 Proteins 0.000 description 2
- 102100023719 Src substrate cortactin Human genes 0.000 description 2
- 108010002321 Tight Junction Proteins Proteins 0.000 description 2
- 102000000591 Tight Junction Proteins Human genes 0.000 description 2
- 102100034686 Tight junction protein ZO-1 Human genes 0.000 description 2
- 102100023486 Vinculin Human genes 0.000 description 2
- 210000002867 adherens junction Anatomy 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 108010013835 arginine glutamate Proteins 0.000 description 2
- 108010092854 aspartyllysine Proteins 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 210000003850 cellular structure Anatomy 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000000280 densification Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010201 enrichment analysis Methods 0.000 description 2
- 108010055671 ezrin Proteins 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 2
- 108010038320 lysylphenylalanine Proteins 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108091005601 modified peptides Proteins 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical group COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 108010005652 splenotritin Proteins 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 101710119042 Actin, cytoplasmic 2 Proteins 0.000 description 1
- PBAMJJXWDQXOJA-FXQIFTODSA-N Ala-Asp-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PBAMJJXWDQXOJA-FXQIFTODSA-N 0.000 description 1
- NKJBKNVQHBZUIX-ACZMJKKPSA-N Ala-Gln-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKJBKNVQHBZUIX-ACZMJKKPSA-N 0.000 description 1
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 1
- BVSGPHDECMJBDE-HGNGGELXSA-N Ala-Glu-His Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N BVSGPHDECMJBDE-HGNGGELXSA-N 0.000 description 1
- HXNNRBHASOSVPG-GUBZILKMSA-N Ala-Glu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HXNNRBHASOSVPG-GUBZILKMSA-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
- MFMDKJIPHSWSBM-GUBZILKMSA-N Ala-Lys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFMDKJIPHSWSBM-GUBZILKMSA-N 0.000 description 1
- BLTRAARCJYVJKV-QEJZJMRPSA-N Ala-Lys-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(O)=O BLTRAARCJYVJKV-QEJZJMRPSA-N 0.000 description 1
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 1
- ZCUFMRIQCPNOHZ-NRPADANISA-N Ala-Val-Gln Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N ZCUFMRIQCPNOHZ-NRPADANISA-N 0.000 description 1
- GXCSUJQOECMKPV-CIUDSAMLSA-N Arg-Ala-Gln Chemical compound C[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GXCSUJQOECMKPV-CIUDSAMLSA-N 0.000 description 1
- VBFJESQBIWCWRL-DCAQKATOSA-N Arg-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCNC(N)=N VBFJESQBIWCWRL-DCAQKATOSA-N 0.000 description 1
- NTAZNGWBXRVEDJ-FXQIFTODSA-N Arg-Asp-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NTAZNGWBXRVEDJ-FXQIFTODSA-N 0.000 description 1
- OZNSCVPYWZRQPY-CIUDSAMLSA-N Arg-Asp-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O OZNSCVPYWZRQPY-CIUDSAMLSA-N 0.000 description 1
- VNFWDYWTSHFRRG-SRVKXCTJSA-N Arg-Gln-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O VNFWDYWTSHFRRG-SRVKXCTJSA-N 0.000 description 1
- NXDXECQFKHXHAM-HJGDQZAQSA-N Arg-Glu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NXDXECQFKHXHAM-HJGDQZAQSA-N 0.000 description 1
- SYAUZLVLXCDRSH-IUCAKERBSA-N Arg-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N SYAUZLVLXCDRSH-IUCAKERBSA-N 0.000 description 1
- OOIMKQRCPJBGPD-XUXIUFHCSA-N Arg-Ile-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O OOIMKQRCPJBGPD-XUXIUFHCSA-N 0.000 description 1
- LVMUGODRNHFGRA-AVGNSLFASA-N Arg-Leu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O LVMUGODRNHFGRA-AVGNSLFASA-N 0.000 description 1
- GMFAGHNRXPSSJS-SRVKXCTJSA-N Arg-Leu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GMFAGHNRXPSSJS-SRVKXCTJSA-N 0.000 description 1
- OTZMRMHZCMZOJZ-SRVKXCTJSA-N Arg-Leu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O OTZMRMHZCMZOJZ-SRVKXCTJSA-N 0.000 description 1
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-N 0.000 description 1
- QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 description 1
- ORXCYAFUCSTQGY-FXQIFTODSA-N Asn-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(=O)N)N ORXCYAFUCSTQGY-FXQIFTODSA-N 0.000 description 1
- BZMWJLLUAKSIMH-FXQIFTODSA-N Asn-Glu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BZMWJLLUAKSIMH-FXQIFTODSA-N 0.000 description 1
- SEKBHZJLARBNPB-GHCJXIJMSA-N Asn-Ile-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O SEKBHZJLARBNPB-GHCJXIJMSA-N 0.000 description 1
- ALHMNHZJBYBYHS-DCAQKATOSA-N Asn-Lys-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ALHMNHZJBYBYHS-DCAQKATOSA-N 0.000 description 1
- 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 1
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 1
- ICDDSTLEMLGSTB-GUBZILKMSA-N Asn-Met-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ICDDSTLEMLGSTB-GUBZILKMSA-N 0.000 description 1
- BYLSYQASFJJBCL-DCAQKATOSA-N Asn-Pro-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BYLSYQASFJJBCL-DCAQKATOSA-N 0.000 description 1
- UXHYOWXTJLBEPG-GSSVUCPTSA-N Asn-Thr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UXHYOWXTJLBEPG-GSSVUCPTSA-N 0.000 description 1
- PBVLJOIPOGUQQP-CIUDSAMLSA-N Asp-Ala-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O PBVLJOIPOGUQQP-CIUDSAMLSA-N 0.000 description 1
- HMQDRBKQMLRCCG-GMOBBJLQSA-N Asp-Arg-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HMQDRBKQMLRCCG-GMOBBJLQSA-N 0.000 description 1
- CELPEWWLSXMVPH-CIUDSAMLSA-N Asp-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O CELPEWWLSXMVPH-CIUDSAMLSA-N 0.000 description 1
- VILLWIDTHYPSLC-PEFMBERDSA-N Asp-Glu-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VILLWIDTHYPSLC-PEFMBERDSA-N 0.000 description 1
- NHSDEZURHWEZPN-SXTJYALSSA-N Asp-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H](CC(=O)O)N NHSDEZURHWEZPN-SXTJYALSSA-N 0.000 description 1
- WNGZKSVJFDZICU-XIRDDKMYSA-N Asp-Leu-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(=O)O)N WNGZKSVJFDZICU-XIRDDKMYSA-N 0.000 description 1
- QNMKWNONJGKJJC-NHCYSSNCSA-N Asp-Leu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O QNMKWNONJGKJJC-NHCYSSNCSA-N 0.000 description 1
- GPPIDDWYKJPRES-YDHLFZDLSA-N Asp-Phe-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O GPPIDDWYKJPRES-YDHLFZDLSA-N 0.000 description 1
- KNDCWFXCFKSEBM-AVGNSLFASA-N Asp-Tyr-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O KNDCWFXCFKSEBM-AVGNSLFASA-N 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- INKFLNZBTSNFON-CIUDSAMLSA-N Gln-Ala-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O INKFLNZBTSNFON-CIUDSAMLSA-N 0.000 description 1
- LJEPDHWNQXPXMM-NHCYSSNCSA-N Gln-Arg-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O LJEPDHWNQXPXMM-NHCYSSNCSA-N 0.000 description 1
- IKDOHQHEFPPGJG-FXQIFTODSA-N Gln-Asp-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IKDOHQHEFPPGJG-FXQIFTODSA-N 0.000 description 1
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 1
- KVXVVDFOZNYYKZ-DCAQKATOSA-N Gln-Gln-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KVXVVDFOZNYYKZ-DCAQKATOSA-N 0.000 description 1
- ZQPOVSJFBBETHQ-CIUDSAMLSA-N Gln-Glu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZQPOVSJFBBETHQ-CIUDSAMLSA-N 0.000 description 1
- XJKAKYXMFHUIHT-AUTRQRHGSA-N Gln-Glu-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N XJKAKYXMFHUIHT-AUTRQRHGSA-N 0.000 description 1
- XKBASPWPBXNVLQ-WDSKDSINSA-N Gln-Gly-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XKBASPWPBXNVLQ-WDSKDSINSA-N 0.000 description 1
- TWTWUBHEWQPMQW-ZPFDUUQYSA-N Gln-Ile-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TWTWUBHEWQPMQW-ZPFDUUQYSA-N 0.000 description 1
- HHQCBFGKQDMWSP-GUBZILKMSA-N Gln-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HHQCBFGKQDMWSP-GUBZILKMSA-N 0.000 description 1
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 1
- JUUNNOLZGVYCJT-JYJNAYRXSA-N Gln-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JUUNNOLZGVYCJT-JYJNAYRXSA-N 0.000 description 1
- DITJVHONFRJKJW-BPUTZDHNSA-N Gln-Trp-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N DITJVHONFRJKJW-BPUTZDHNSA-N 0.000 description 1
- FTMLQFPULNGION-ZVZYQTTQSA-N Gln-Val-Trp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O FTMLQFPULNGION-ZVZYQTTQSA-N 0.000 description 1
- 206010051920 Glomerulonephropathy Diseases 0.000 description 1
- FHPXTPQBODWBIY-CIUDSAMLSA-N Glu-Ala-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHPXTPQBODWBIY-CIUDSAMLSA-N 0.000 description 1
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 1
- RCCDHXSRMWCOOY-GUBZILKMSA-N Glu-Arg-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCCDHXSRMWCOOY-GUBZILKMSA-N 0.000 description 1
- CGYDXNKRIMJMLV-GUBZILKMSA-N Glu-Arg-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CGYDXNKRIMJMLV-GUBZILKMSA-N 0.000 description 1
- OJGLIOXAKGFFDW-SRVKXCTJSA-N Glu-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N OJGLIOXAKGFFDW-SRVKXCTJSA-N 0.000 description 1
- DYFJZDDQPNIPAB-NHCYSSNCSA-N Glu-Arg-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O DYFJZDDQPNIPAB-NHCYSSNCSA-N 0.000 description 1
- XXCDTYBVGMPIOA-FXQIFTODSA-N Glu-Asp-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XXCDTYBVGMPIOA-FXQIFTODSA-N 0.000 description 1
- WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 1
- LGYZYFFDELZWRS-DCAQKATOSA-N Glu-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O LGYZYFFDELZWRS-DCAQKATOSA-N 0.000 description 1
- CUXJIASLBRJOFV-LAEOZQHASA-N Glu-Gly-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUXJIASLBRJOFV-LAEOZQHASA-N 0.000 description 1
- QIQABBIDHGQXGA-ZPFDUUQYSA-N Glu-Ile-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QIQABBIDHGQXGA-ZPFDUUQYSA-N 0.000 description 1
- DWBBKNPKDHXIAC-SRVKXCTJSA-N Glu-Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCC(O)=O DWBBKNPKDHXIAC-SRVKXCTJSA-N 0.000 description 1
- IOUQWHIEQYQVFD-JYJNAYRXSA-N Glu-Leu-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IOUQWHIEQYQVFD-JYJNAYRXSA-N 0.000 description 1
- SWRVAQHFBRZVNX-GUBZILKMSA-N Glu-Lys-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SWRVAQHFBRZVNX-GUBZILKMSA-N 0.000 description 1
- BCYGDJXHAGZNPQ-DCAQKATOSA-N Glu-Lys-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O BCYGDJXHAGZNPQ-DCAQKATOSA-N 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- ZTVGZOIBLRPQNR-KKUMJFAQSA-N Glu-Met-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZTVGZOIBLRPQNR-KKUMJFAQSA-N 0.000 description 1
- 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 1
- IDEODOAVGCMUQV-GUBZILKMSA-N Glu-Ser-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IDEODOAVGCMUQV-GUBZILKMSA-N 0.000 description 1
- QCMVGXDELYMZET-GLLZPBPUSA-N Glu-Thr-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QCMVGXDELYMZET-GLLZPBPUSA-N 0.000 description 1
- MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 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
- QGZSAHIZRQHCEQ-QWRGUYRKSA-N Gly-Asp-Tyr Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QGZSAHIZRQHCEQ-QWRGUYRKSA-N 0.000 description 1
- DGKBSGNCMCLDSL-BYULHYEWSA-N Gly-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN DGKBSGNCMCLDSL-BYULHYEWSA-N 0.000 description 1
- UESJMAMHDLEHGM-NHCYSSNCSA-N Gly-Ile-Leu Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O UESJMAMHDLEHGM-NHCYSSNCSA-N 0.000 description 1
- FHQRLHFYVZAQHU-IUCAKERBSA-N Gly-Lys-Gln Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O FHQRLHFYVZAQHU-IUCAKERBSA-N 0.000 description 1
- RIYIFUFFFBIOEU-KBPBESRZSA-N Gly-Tyr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 RIYIFUFFFBIOEU-KBPBESRZSA-N 0.000 description 1
- KYMUEAZVLPRVAE-GUBZILKMSA-N His-Asn-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KYMUEAZVLPRVAE-GUBZILKMSA-N 0.000 description 1
- NWGXCPUKPVISSJ-AVGNSLFASA-N His-Gln-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N NWGXCPUKPVISSJ-AVGNSLFASA-N 0.000 description 1
- UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 description 1
- WSXNWASHQNSMRX-GVXVVHGQSA-N His-Val-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N WSXNWASHQNSMRX-GVXVVHGQSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101000773237 Homo sapiens Actin, cytoplasmic 2 Proteins 0.000 description 1
- 101000916264 Homo sapiens Catenin delta-1 Proteins 0.000 description 1
- 101000829367 Homo sapiens Src substrate cortactin Proteins 0.000 description 1
- 101000802356 Homo sapiens Tight junction protein ZO-1 Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000003623 Hypoalbuminemia Diseases 0.000 description 1
- FJWYJQRCVNGEAQ-ZPFDUUQYSA-N Ile-Asn-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N FJWYJQRCVNGEAQ-ZPFDUUQYSA-N 0.000 description 1
- IDAHFEPYTJJZFD-PEFMBERDSA-N Ile-Asp-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N IDAHFEPYTJJZFD-PEFMBERDSA-N 0.000 description 1
- QSPLUJGYOPZINY-ZPFDUUQYSA-N Ile-Asp-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N QSPLUJGYOPZINY-ZPFDUUQYSA-N 0.000 description 1
- BSWLQVGEVFYGIM-ZPFDUUQYSA-N Ile-Gln-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N BSWLQVGEVFYGIM-ZPFDUUQYSA-N 0.000 description 1
- OVPYIUNCVSOVNF-KQXIARHKSA-N Ile-Gln-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N OVPYIUNCVSOVNF-KQXIARHKSA-N 0.000 description 1
- OVPYIUNCVSOVNF-ZPFDUUQYSA-N Ile-Gln-Pro Natural products CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O OVPYIUNCVSOVNF-ZPFDUUQYSA-N 0.000 description 1
- WUKLZPHVWAMZQV-UKJIMTQDSA-N Ile-Glu-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N WUKLZPHVWAMZQV-UKJIMTQDSA-N 0.000 description 1
- GLYJPWIRLBAIJH-FQUUOJAGSA-N Ile-Lys-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N GLYJPWIRLBAIJH-FQUUOJAGSA-N 0.000 description 1
- GLYJPWIRLBAIJH-UHFFFAOYSA-N Ile-Lys-Pro Natural products CCC(C)C(N)C(=O)NC(CCCCN)C(=O)N1CCCC1C(O)=O GLYJPWIRLBAIJH-UHFFFAOYSA-N 0.000 description 1
- AKOYRLRUFBZOSP-BJDJZHNGSA-N Ile-Lys-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N AKOYRLRUFBZOSP-BJDJZHNGSA-N 0.000 description 1
- NAFIFZNBSPWYOO-RWRJDSDZSA-N Ile-Thr-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N NAFIFZNBSPWYOO-RWRJDSDZSA-N 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- JUWJEAPUNARGCF-DCAQKATOSA-N Leu-Arg-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O JUWJEAPUNARGCF-DCAQKATOSA-N 0.000 description 1
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 1
- OXKYZSRZKBTVEY-ZPFDUUQYSA-N Leu-Asn-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OXKYZSRZKBTVEY-ZPFDUUQYSA-N 0.000 description 1
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 1
- WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 description 1
- LLBQJYDYOLIQAI-JYJNAYRXSA-N Leu-Glu-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LLBQJYDYOLIQAI-JYJNAYRXSA-N 0.000 description 1
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 1
- AUBMZAMQCOYSIC-MNXVOIDGSA-N Leu-Ile-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O AUBMZAMQCOYSIC-MNXVOIDGSA-N 0.000 description 1
- OMHLATXVNQSALM-FQUUOJAGSA-N Leu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(C)C)N OMHLATXVNQSALM-FQUUOJAGSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- RZXLZBIUTDQHJQ-SRVKXCTJSA-N Leu-Lys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O RZXLZBIUTDQHJQ-SRVKXCTJSA-N 0.000 description 1
- ZAVCJRJOQKIOJW-KKUMJFAQSA-N Leu-Phe-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=CC=C1 ZAVCJRJOQKIOJW-KKUMJFAQSA-N 0.000 description 1
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 1
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-N 0.000 description 1
- BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 description 1
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 1
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 1
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 1
- VHNOAIFVYUQOOY-XUXIUFHCSA-N Lys-Arg-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VHNOAIFVYUQOOY-XUXIUFHCSA-N 0.000 description 1
- ZQCVMVCVPFYXHZ-SRVKXCTJSA-N Lys-Asn-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN ZQCVMVCVPFYXHZ-SRVKXCTJSA-N 0.000 description 1
- WTZUSCUIVPVCRH-SRVKXCTJSA-N Lys-Gln-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WTZUSCUIVPVCRH-SRVKXCTJSA-N 0.000 description 1
- GRADYHMSAUIKPS-DCAQKATOSA-N Lys-Glu-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O GRADYHMSAUIKPS-DCAQKATOSA-N 0.000 description 1
- CANPXOLVTMKURR-WEDXCCLWSA-N Lys-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN CANPXOLVTMKURR-WEDXCCLWSA-N 0.000 description 1
- SLQJJFAVWSZLBL-BJDJZHNGSA-N Lys-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN SLQJJFAVWSZLBL-BJDJZHNGSA-N 0.000 description 1
- IVFUVMSKSFSFBT-NHCYSSNCSA-N Lys-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN IVFUVMSKSFSFBT-NHCYSSNCSA-N 0.000 description 1
- XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 1
- XOQMURBBIXRRCR-SRVKXCTJSA-N Lys-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN XOQMURBBIXRRCR-SRVKXCTJSA-N 0.000 description 1
- ZJWIXBZTAAJERF-IHRRRGAJSA-N Lys-Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N ZJWIXBZTAAJERF-IHRRRGAJSA-N 0.000 description 1
- ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 1
- YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 1
- WINFHLHJTRGLCV-BZSNNMDCSA-N Lys-Tyr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=C(O)C=C1 WINFHLHJTRGLCV-BZSNNMDCSA-N 0.000 description 1
- YRAWWKUTNBILNT-FXQIFTODSA-N Met-Ala-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YRAWWKUTNBILNT-FXQIFTODSA-N 0.000 description 1
- JQECLVNLAZGHRQ-CIUDSAMLSA-N Met-Asp-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(N)=O JQECLVNLAZGHRQ-CIUDSAMLSA-N 0.000 description 1
- WWWGMQHQSAUXBU-BQBZGAKWSA-N Met-Gly-Asn Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(N)=O WWWGMQHQSAUXBU-BQBZGAKWSA-N 0.000 description 1
- UNPGTBHYKJOCCZ-DCAQKATOSA-N Met-Lys-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O UNPGTBHYKJOCCZ-DCAQKATOSA-N 0.000 description 1
- OXIWIYOJVNOKOV-SRVKXCTJSA-N Met-Met-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(O)=O)CCCNC(N)=N OXIWIYOJVNOKOV-SRVKXCTJSA-N 0.000 description 1
- WXXNVZMWHOLNRJ-AVGNSLFASA-N Met-Pro-Lys Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O WXXNVZMWHOLNRJ-AVGNSLFASA-N 0.000 description 1
- 102100027869 Moesin Human genes 0.000 description 1
- 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 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- HCTXJGRYAACKOB-SRVKXCTJSA-N Phe-Asn-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N HCTXJGRYAACKOB-SRVKXCTJSA-N 0.000 description 1
- MGBRZXXGQBAULP-DRZSPHRISA-N Phe-Glu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 MGBRZXXGQBAULP-DRZSPHRISA-N 0.000 description 1
- APJPXSFJBMMOLW-KBPBESRZSA-N Phe-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 APJPXSFJBMMOLW-KBPBESRZSA-N 0.000 description 1
- RSPUIENXSJYZQO-JYJNAYRXSA-N Phe-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 RSPUIENXSJYZQO-JYJNAYRXSA-N 0.000 description 1
- XOHJOMKCRLHGCY-UNQGMJICSA-N Phe-Pro-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOHJOMKCRLHGCY-UNQGMJICSA-N 0.000 description 1
- QTDBZORPVYTRJU-KKXDTOCCSA-N Phe-Tyr-Ala 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](C)C(O)=O QTDBZORPVYTRJU-KKXDTOCCSA-N 0.000 description 1
- SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 description 1
- SFECXGVELZFBFJ-VEVYYDQMSA-N Pro-Asp-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SFECXGVELZFBFJ-VEVYYDQMSA-N 0.000 description 1
- UEHYFUCOGHWASA-HJGDQZAQSA-N Pro-Glu-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 UEHYFUCOGHWASA-HJGDQZAQSA-N 0.000 description 1
- BBFRBZYKHIKFBX-GMOBBJLQSA-N Pro-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@@H]1CCCN1 BBFRBZYKHIKFBX-GMOBBJLQSA-N 0.000 description 1
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- VPBQDHMASPJHGY-JYJNAYRXSA-N Pro-Trp-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CO)C(=O)O VPBQDHMASPJHGY-JYJNAYRXSA-N 0.000 description 1
- 102100022127 Radixin Human genes 0.000 description 1
- SRTCFKGBYBZRHA-ACZMJKKPSA-N Ser-Ala-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SRTCFKGBYBZRHA-ACZMJKKPSA-N 0.000 description 1
- 101710160291 Src substrate cortactin Proteins 0.000 description 1
- GLQFKOVWXPPFTP-VEVYYDQMSA-N Thr-Arg-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GLQFKOVWXPPFTP-VEVYYDQMSA-N 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
- JQAWYCUUFIMTHE-WLTAIBSBSA-N Thr-Gly-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JQAWYCUUFIMTHE-WLTAIBSBSA-N 0.000 description 1
- VUSAEKOXGNEYNE-PBCZWWQYSA-N Thr-His-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O VUSAEKOXGNEYNE-PBCZWWQYSA-N 0.000 description 1
- URPSJRMWHQTARR-MBLNEYKQSA-N Thr-Ile-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O URPSJRMWHQTARR-MBLNEYKQSA-N 0.000 description 1
- AMXMBCAXAZUCFA-RHYQMDGZSA-N Thr-Leu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMXMBCAXAZUCFA-RHYQMDGZSA-N 0.000 description 1
- YJVJPJPHHFOVMG-VEVYYDQMSA-N Thr-Met-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O YJVJPJPHHFOVMG-VEVYYDQMSA-N 0.000 description 1
- 108050001370 Tight junction protein ZO-1 Proteins 0.000 description 1
- CPZTZWFFGVKHEA-SZMVWBNQSA-N Trp-Gln-His Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N CPZTZWFFGVKHEA-SZMVWBNQSA-N 0.000 description 1
- RRVUOLRWIZXBRQ-IHPCNDPISA-N Trp-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RRVUOLRWIZXBRQ-IHPCNDPISA-N 0.000 description 1
- GHUNBABNQPIETG-MELADBBJSA-N Tyr-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O GHUNBABNQPIETG-MELADBBJSA-N 0.000 description 1
- SLCSPPCQWUHPPO-JYJNAYRXSA-N Tyr-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SLCSPPCQWUHPPO-JYJNAYRXSA-N 0.000 description 1
- LHTGRUZSZOIAKM-SOUVJXGZSA-N Tyr-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O LHTGRUZSZOIAKM-SOUVJXGZSA-N 0.000 description 1
- LRHBBGDMBLFYGL-FHWLQOOXSA-N Tyr-Phe-Glu Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=C(O)C=C1 LRHBBGDMBLFYGL-FHWLQOOXSA-N 0.000 description 1
- SQUMHUZLJDUROQ-YDHLFZDLSA-N Tyr-Val-Asp 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](CC(O)=O)C(O)=O SQUMHUZLJDUROQ-YDHLFZDLSA-N 0.000 description 1
- VUTHNLMCXKLLFI-LAEOZQHASA-N Val-Asp-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VUTHNLMCXKLLFI-LAEOZQHASA-N 0.000 description 1
- BRPKEERLGYNCNC-NHCYSSNCSA-N Val-Glu-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N BRPKEERLGYNCNC-NHCYSSNCSA-N 0.000 description 1
- SZTTYWIUCGSURQ-AUTRQRHGSA-N Val-Glu-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SZTTYWIUCGSURQ-AUTRQRHGSA-N 0.000 description 1
- CHWRZUGUMAMTFC-IHRRRGAJSA-N Val-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CNC=N1 CHWRZUGUMAMTFC-IHRRRGAJSA-N 0.000 description 1
- IJGPOONOTBNTFS-GVXVVHGQSA-N Val-Lys-Glu Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O IJGPOONOTBNTFS-GVXVVHGQSA-N 0.000 description 1
- QPPZEDOTPZOSEC-RCWTZXSCSA-N Val-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C)C)N)O QPPZEDOTPZOSEC-RCWTZXSCSA-N 0.000 description 1
- DEGUERSKQBRZMZ-FXQIFTODSA-N Val-Ser-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DEGUERSKQBRZMZ-FXQIFTODSA-N 0.000 description 1
- HWNYVQMOLCYHEA-IHRRRGAJSA-N Val-Ser-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N HWNYVQMOLCYHEA-IHRRRGAJSA-N 0.000 description 1
- VBTFUDNTMCHPII-FKBYEOEOSA-N Val-Trp-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O VBTFUDNTMCHPII-FKBYEOEOSA-N 0.000 description 1
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 1
- 108090000384 Vinculin Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000007622 bioinformatic analysis Methods 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 108010031971 delta catenin Proteins 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108010071525 moesin Proteins 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 108010025488 pinealon Proteins 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010048484 radixin Proteins 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/34—Genitourinary disorders
- G01N2800/347—Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明公开了一种定量检测蛋白质EZR的T567位点的磷酸化水平的试剂在制备膜性肾病诊断试剂中的应用。申请人在研究过程中发现,EZR磷酸化位点T567的磷酸化水平在IMN组中相比于对照组都存在显著的下调,可能是随着疾病进展而逐渐下降的。T567的磷酸化水平下调可能参与了IMN疾病进展过程中足细胞的损伤。而切片的免疫组织化学染色强度及细胞阳性率统计结果进一步证明,EZRT567位点的磷酸化水平在IMN患者的肾活检组织中确实是下降的,因此,可以通过能够定量检测蛋白质EZR的T567位点的磷酸化水平的试剂来诊断膜性肾病。
Description
技术领域
本申请涉及肾病技术领域,尤其是涉及磷酸化蛋白质在膜性肾病中的应用。
背景技术
膜性肾病(membranous nephropathy,MN)是成人肾病综合征最常见的原因。根据病因不同,MN可以分为特发性膜性肾病(idiopathic membranous nephropathy,IMN)和继发性膜性肾病(secondary membranous nephropathy,SMN),其中IMN约占75%,病因不明;SMN病因比较明确,肿瘤、感染、药物、自身免疫性疾病如系统性红斑狼疮等可导致SMN。MN患者通常表现为严重蛋白尿、水肿、低蛋白血症、高脂血症,诊断依赖肾脏活检病理,其病理诊断特征包括有:肾小球毛细血管壁增厚,免疫荧光可见IgG、C3沿着毛细血管壁沉积,电镜显示肾小球脏层上皮细胞下电子致密物形成;但是IMN需排除继发性因素后才能诊断。
目前IMN的病因及发病机制并不十分明确,可能和遗传基因、免疫、环境因素有关。虽然在IMN疾病标志物及发病机制方面有了一定的研究成果,但是对该疾病关键的触发源头、补体激活机制及导致足细胞损伤的具体分子机制尚未完全明确,这也给IMN的诊断和临床治疗带来一定的困难,患者一旦进入ESRD阶段将会面临更为严重的生理心理以及社会负担。因此寻找新的视角来进一步研究膜性肾病的诊断标志物或者潜在的治疗干预靶点。
发明内容
本申请旨在至少解决现有技术中存在的技术问题之一。为此,本申请提出一种磷酸化蛋白质作为膜性肾病的诊断标志物,利用能够定量检测该蛋白的特定位点的磷酸化水平的试剂可以有效地诊断膜性肾病或作为潜在的治疗干预靶点。
本申请的第一方面,提供定量检测蛋白质EZR的T567位点的磷酸化水平的试剂在制备膜性肾病诊断试剂中的应用。
根据本申请实施例的应用,至少具有如下有益效果:
肾小球足细胞是高度分化的细胞,胞体具有许多突起,称为足突。足细胞对肾小球滤过屏障的选择通透性十分重要并且足细胞发挥功能主要基于细胞结构的动态调节,特别是足突结构的调节。EZR(ezrin,Gene ID:7430)是肌动蛋白-质膜连接蛋白,主要存在于足细胞足突,EZR的磷酸化位点T567的磷酸化在维持细胞形态结构,动态调节B细胞受体迁移,8-细胞胚胎紧密化,凋亡信号转导等方面发挥重要作用。而申请人在研究过程中发现,EZR磷酸化位点T567的磷酸化水平在IMN组中相比于对照组存在显著的下调,可能是随着疾病进展而逐渐下降的。T567的磷酸化水平下调可能参与了IMN疾病进展过程中足细胞的损伤。而切片的免疫组织化学染色强度及细胞阳性率统计结果进一步证明,EZR的T567位点的磷酸化水平在IMN患者的肾活检组织中确实是下降的,因此,可以通过能够定量检测蛋白质EZR的T567位点的磷酸化水平的试剂来诊断膜性肾病。
其中,EZR的氨基酸序列如下所示:
MPKPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLHYVDNKGFPTWLKLDKKVSAQEVRKENPLQFKFRAKFYPEDVAEELIQDITQKLFFLQVKEGILSDEIYCPPETAVLLGSYAVQAKFGDYNKEVHKSGYLSSERLIPQRVMDQHKLTRDQWEDRIQVWHAEHRGMLKDNAMLEYLKIAQDLEMYGINYFEIKNKKGTDLWLGVDALGLNIYEKDDKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILQLCMGNHELYMRRRKPDTIEVQQMKAQAREEKHQKQLERQQLETEKKRRETVEREKEQMMREKEELMLRLQDYEEKTKKAERELSEQIQRALQLEEERKRAQEEAERLEADRMAALRAKEELERQAVDQIKSQEQLAAELAEYTAKIALLEEARRRKEDEVEEWQHRAKEAQDDLVKTKEELHLVMTAPPPPPPPVYEPVSYHVQESLQDEGAEPTGYSAELSSEGIRDDRNEEKRITEAEKNERVQRQLLTLSSELSQARDENKRTHNDIIHNENMRQGRDKYKTLRQIRQGNTKQRIDEFEAL(SEQ ID No.1)。
在本申请的一些实施方式中,膜性肾病为特发性膜性肾病。
在本申请的一些实施方式中,试剂包括蛋白质EZR的T567位点的磷酸化抗体。其中,磷酸化抗体可以是单克隆抗体也可以是多克隆抗体。可以理解的是,试剂也可以是本领域所知的其它可以定量检测蛋白质特定位点磷酸化水平的试剂。
在本申请的一些实施方式中,蛋白质EZR来源于活体肾组织。利用穿刺或外科手术的方法从患者的肾脏中获得少许的肾脏活体组织进行蛋白质EZR的T567的磷酸化水平的定量检测。
本申请的第二方面,提供蛋白质EZR的T567位点作为靶点在筛选或制备用于治疗膜性肾病的药物中的应用。通过备选药物是否能够对EZR的T567位点的磷酸化水平进行改变,具体而言是是否能够上调EZR的T567位点的磷酸化水平,判断其是否参与足细胞的损伤修复,从而确定能否用作治疗膜性肾病的药物。如果可以上调EZR的T567位点的磷酸化水平,则有可能参与足细胞的损伤修复,可能能够用于治疗膜性肾病,特别是特发性膜性肾病。
本申请的附加方面和优点将在下面的描述中部分给出,部分将从下面的描述中变得明显,或通过本申请的实践了解到。
附图说明
图1是KEGG通路注释及富集分析结果,其中,a、b、c分别是Ⅱ期IMN组/对照组、Ⅱ期IMN组/Ⅲ期IMN组、Ⅲ期IMN组/对照组的差异蛋白质富集的通路。
图2是利用三个免疫相关通路对差异磷酸化蛋白质的筛选结果,其中,A是对6个分析方法分别筛选出的10种关键蛋白质取交集的结果,B是三个通路上的差异磷酸化蛋白质形成的互作网路图。
图3中EZR(T567)免疫组化实验结果,其中,A是对照组的免疫组化实验结果,B是Ⅱ期IMN患者的免疫组化实验结果,C是阳性细胞率的统计比较结果。
具体实施方式
以下将结合实施例对本申请的构思及产生的技术效果进行清楚、完整地描述,以充分地理解本申请的目的、特征和效果。显然,所描述的实施例只是本申请的一部分实施例,而不是全部实施例,基于本申请的实施例,本领域的技术人员在不付出创造性劳动的前提下所获得的其他实施例,均属于本申请保护的范围。
下面详细描述本申请的实施例,描述的实施例是示例性的,仅用于解释本申请,而不能理解为对本申请的限制。
在本申请的描述中,若干的含义是一个以上,多个的含义是两个以上,大于、小于、超过等理解为不包括本数,以上、以下、以内等理解为包括本数。如果有描述到第一、第二只是用于区分技术特征为目的,而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量或者隐含指明所指示的技术特征的先后关系。
本申请的描述中,参考术语“一个实施例”、“一些实施例”、“示意性实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本申请的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不一定指的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
实施例1:差异磷酸化蛋白质的筛选
一、IMN患者及对照组的选取
IMN组为确诊为IMN的16例患者(其中Ⅱ期IMN 11例,Ⅲ期IMN 5例,因此分为Ⅱ期IMN组和Ⅲ期IMN组),由于正常健康肾组织的来源非常困难,所以对照组选择病理确诊为轻微肾小球异常的10例患者,在该实验中可以视为健康人的对照组,性别年龄等基本条件与选取的IMN患者相匹配。IMN患者的诊断都是通过肾活检病理诊断(光学显微镜及电子显微镜病理)明确的,临床上排除肿瘤、感染、药物、自身免疫性疾病如系统性红斑狼疮等继发性MN。收集IMN组和对照组入院时的肾活检组织样本及临床资料、实验室相关检验结果以及病理检测报告图片。
二、IMN患者组及对照组的差异磷酸化修饰的蛋白质分析
(1)通过质谱分析技术检测修饰肽段在每组肾活检样本(混样)中对应的信号丰度,通过非标定量计算方法得到修饰位点在每组样本中的intensity,根据不同样本之间修饰位点intensity得到每组样本的相对定量值。当差异修饰肽段在两组样本中相对定量变化超过2倍时作为显著上调的变化阈值,小于1/2倍作为显著下调的变化阈值。鉴定出Ⅱ期IMN组/对照组、Ⅱ期IMN组/Ⅲ期IMN组、Ⅲ期IMN组/对照组这三个比较组各自的差异磷酸化修饰的蛋白质。
(2)针对鉴定到的每个比较组的差异磷酸化修饰蛋白质进行详细的生物信息学分析
1)KEGG通路注释及富集分析
KEGG(Kyoto Encyclopedia of Genes and Genomes)能够将当前已知的蛋白质的相互作用网络信息等进行综合,通过使用KAAS对提交的差异磷酸化修饰蛋白质分别进行注释,之后通过KEGG mapper将注释过的蛋白质匹配到数据库中对应的信号转导通路中。同时通路富集检验P值小于0.05被认为是显著富集。
2)构建差异磷酸化修饰蛋白质相互作用网络
将不同比较组中鉴定到的差异磷酸化修饰蛋白质数据库编号或蛋白序列,通过与STRING蛋白互作网络数据库比对后,得到差异磷酸化修饰蛋白质相互作用关系。
图1中a、b、c分别是Ⅱ期IMN组/对照组、Ⅱ期IMN组/Ⅲ期IMN组、Ⅲ期IMN组/对照组的差异磷酸化蛋白质富集的通路。从图中结果结合相关文献报道,将紧密连接(tightjunction),粘着连接(adherens junction)以及白细胞跨内皮迁移(leukocytetransendothelial migration)作为上述三个比较组中较为关键的三条与免疫反应有关的通路。
对每个比较组内的上述三个通路中的所有的差异磷酸化蛋白质采用STRINGdatabase(v.11.0)建立网络互作图,然后在Cytoscape(v.3.7.2)软件中可视化展示,通过该软件CytoHubba插件内的6种(Degree,Maximum neighborhood component(MNC),Edgepercolated component(EPC),Closeness centrality,Radiality centrality,Stresscentrality)分析方法鉴定到的排名前十位的关键蛋白质,结果如表1所示。
表1.关键蛋白质
对上述排名前十位的关键蛋白质取交集后得出7个重叠的可能是更关键的蛋白质,结果如图2的A所示。而三个比较组中紧密连接(tight junction),粘着连接(adherensjunction)以及白细胞跨内皮迁移(leukocyte transendothelial migration)通路上的差异磷酸化蛋白质形成的互作网路图如图2的B所示。筛选出的7个关键蛋白质分别是VCL(vinculin)、TJP1(tight junction protein ZO-1)、EGFR(epidermal growth factorreceptor)、EZR(ezrin)、CTNND1(catenin delta-1)、ACTG1(actin,cytoplasmic 2)、CTTN(Src substrate cortactin)。
进一步在三个比较组的差异磷酸化蛋白质数据鉴定结果中对上述7个蛋白质的磷酸化的表达进行查询,发现EZR磷酸化位点T567的磷酸化水平在Ⅱ期IMN/对照组(比值0.215)和Ⅲ期IMN/对照组(比值0.195)中都下调,而且,由于在Ⅲ期IMN/对照组中磷酸化水平下降的更多,推测该位点磷酸化可能是随着疾病进展而逐渐下降的,因此对蛋白质EZR的磷酸化位点T567进行了进一步讨论与研究。
肾小球足细胞是高度分化的细胞,胞体具有许多突起,称为足突。足细胞对肾小球滤过屏障的选择通透性十分重要并且足细胞发挥功能主要基于细胞结构的动态调节,特别是足突结构的调节。EZR是肌动蛋白-质膜连接蛋白,主要存在于足细胞足突,EZR的磷酸化位点T567的磷酸化在维持细胞形态结构、动态调节B细胞受体迁移、8-细胞胚胎紧密化、凋亡信号转导等方面发挥重要作用。以上研究提示EZR蛋白的T567位点磷酸化水平降低可能参与了膜性肾病中足细胞的损伤过程。而结合实施例1中的结果进一步可以证明,EZR磷酸化位点T567的磷酸化水平下调可能参与了IMN疾病进展过程中足细胞的损伤,EZR磷酸化位点T567可能是该疾病的潜在治疗干预靶点或生物学标志物。免疫组化实验验证
使用EZR(T567)免疫组化抗体(phospho-Ezrin(Thr567)/Radixin(Thr564)/Moesin(Thr558)(48G2)rabbit monoclonal antibody,购于Cell Signaling Technology公司,货号3726)对磷酸化EZR(T567)进行了实验组Ⅱ期IMN患者(10例)的肾活检组织石蜡切片上的免疫组织化学验证,并和对照组(5例,病理确诊为轻微肾小球异常的患者)的结果进行比较(实验方法参考抗体的使用说明书),结果如图3所示,其中,A是对照组的免疫组化实验结果,B是Ⅱ期IMN患者的免疫组化实验结果,C是阳性细胞率的统计比较结果(CG:对照组,MNⅡ:实验组)。从图中可以看出,切片的免疫组织化学染色强度在实验组和对照组之间存在比较明显的差异,而细胞阳性率统计结果则进一步表明两个组中EZR(T567)存在显著的统计学差异(p<0.001),综合图3的结果可以看出,EZR在T567位点的磷酸化水平在Ⅱ期IMN患者的肾活检组织中存在显著的下降,与磷酸化组学的检测结果所反映的现象一致。
此外,Ste20样激酶(Ste20-like kinase,SLK)的底物之一是EZR,它可以磷酸化蛋白质EZR的T567位点,实验中发现,足细胞SLK特异性敲除的小鼠表现为蛋白质EZR的T567位点磷酸化水平下降,同时伴随着肾小球足细胞足突增宽或消失、蛋白尿增加等。与肾病小鼠相比,足细胞SLK特异性敲除后会出现更严重的蛋白尿,肾小球足细胞数量减少,蛋白质EZR的T567位点磷酸化水平也下降,因而足细胞完整的细胞骨架的维持依赖于磷酸化的EZR。根据上述实验结果可以判断,在膜性肾病中提升蛋白质EZR的T567位点的磷酸化水平同样可能有助于缓解足细胞结构破坏,从而对肾小球滤过屏障起到一定的维护作用,进而帮助改善或者减轻肾脏病的临床症状如蛋白尿,达到治疗膜性肾病的目的。因此,可以通过验证待测药物是否能够上调EZR的T567位点的磷酸化水平来判断其是否可以作为膜性肾病的治疗药物,从而完成药物筛选;或以此来制备具有相应治疗作用的膜性肾病的药物。
上面结合实施例对本申请作了详细说明,但是本申请不限于上述实施例,在所属技术领域普通技术人员所具备的知识范围内,还可以在不脱离本申请宗旨的前提下作出各种变化。此外,在不冲突的情况下,本申请的实施例及实施例中的特征可以相互组合。
SEQUENCE LISTING
<110> 深圳临研医学有限公司
<120> 磷酸化蛋白质在膜性肾病中的应用
<130> 1
<160> 1
<170> PatentIn version 3.5
<210> 1
<211> 586
<212> PRT
<213> homo sapiens
<400> 1
Met Pro Lys Pro Ile Asn Val Arg Val Thr Thr Met Asp Ala Glu Leu
1 5 10 15
Glu Phe Ala Ile Gln Pro Asn Thr Thr Gly Lys Gln Leu Phe Asp Gln
20 25 30
Val Val Lys Thr Ile Gly Leu Arg Glu Val Trp Tyr Phe Gly Leu His
35 40 45
Tyr Val Asp Asn Lys Gly Phe Pro Thr Trp Leu Lys Leu Asp Lys Lys
50 55 60
Val Ser Ala Gln Glu Val Arg Lys Glu Asn Pro Leu Gln Phe Lys Phe
65 70 75 80
Arg Ala Lys Phe Tyr Pro Glu Asp Val Ala Glu Glu Leu Ile Gln Asp
85 90 95
Ile Thr Gln Lys Leu Phe Phe Leu Gln Val Lys Glu Gly Ile Leu Ser
100 105 110
Asp Glu Ile Tyr Cys Pro Pro Glu Thr Ala Val Leu Leu Gly Ser Tyr
115 120 125
Ala Val Gln Ala Lys Phe Gly Asp Tyr Asn Lys Glu Val His Lys Ser
130 135 140
Gly Tyr Leu Ser Ser Glu Arg Leu Ile Pro Gln Arg Val Met Asp Gln
145 150 155 160
His Lys Leu Thr Arg Asp Gln Trp Glu Asp Arg Ile Gln Val Trp His
165 170 175
Ala Glu His Arg Gly Met Leu Lys Asp Asn Ala Met Leu Glu Tyr Leu
180 185 190
Lys Ile Ala Gln Asp Leu Glu Met Tyr Gly Ile Asn Tyr Phe Glu Ile
195 200 205
Lys Asn Lys Lys Gly Thr Asp Leu Trp Leu Gly Val Asp Ala Leu Gly
210 215 220
Leu Asn Ile Tyr Glu Lys Asp Asp Lys Leu Thr Pro Lys Ile Gly Phe
225 230 235 240
Pro Trp Ser Glu Ile Arg Asn Ile Ser Phe Asn Asp Lys Lys Phe Val
245 250 255
Ile Lys Pro Ile Asp Lys Lys Ala Pro Asp Phe Val Phe Tyr Ala Pro
260 265 270
Arg Leu Arg Ile Asn Lys Arg Ile Leu Gln Leu Cys Met Gly Asn His
275 280 285
Glu Leu Tyr Met Arg Arg Arg Lys Pro Asp Thr Ile Glu Val Gln Gln
290 295 300
Met Lys Ala Gln Ala Arg Glu Glu Lys His Gln Lys Gln Leu Glu Arg
305 310 315 320
Gln Gln Leu Glu Thr Glu Lys Lys Arg Arg Glu Thr Val Glu Arg Glu
325 330 335
Lys Glu Gln Met Met Arg Glu Lys Glu Glu Leu Met Leu Arg Leu Gln
340 345 350
Asp Tyr Glu Glu Lys Thr Lys Lys Ala Glu Arg Glu Leu Ser Glu Gln
355 360 365
Ile Gln Arg Ala Leu Gln Leu Glu Glu Glu Arg Lys Arg Ala Gln Glu
370 375 380
Glu Ala Glu Arg Leu Glu Ala Asp Arg Met Ala Ala Leu Arg Ala Lys
385 390 395 400
Glu Glu Leu Glu Arg Gln Ala Val Asp Gln Ile Lys Ser Gln Glu Gln
405 410 415
Leu Ala Ala Glu Leu Ala Glu Tyr Thr Ala Lys Ile Ala Leu Leu Glu
420 425 430
Glu Ala Arg Arg Arg Lys Glu Asp Glu Val Glu Glu Trp Gln His Arg
435 440 445
Ala Lys Glu Ala Gln Asp Asp Leu Val Lys Thr Lys Glu Glu Leu His
450 455 460
Leu Val Met Thr Ala Pro Pro Pro Pro Pro Pro Pro Val Tyr Glu Pro
465 470 475 480
Val Ser Tyr His Val Gln Glu Ser Leu Gln Asp Glu Gly Ala Glu Pro
485 490 495
Thr Gly Tyr Ser Ala Glu Leu Ser Ser Glu Gly Ile Arg Asp Asp Arg
500 505 510
Asn Glu Glu Lys Arg Ile Thr Glu Ala Glu Lys Asn Glu Arg Val Gln
515 520 525
Arg Gln Leu Leu Thr Leu Ser Ser Glu Leu Ser Gln Ala Arg Asp Glu
530 535 540
Asn Lys Arg Thr His Asn Asp Ile Ile His Asn Glu Asn Met Arg Gln
545 550 555 560
Gly Arg Asp Lys Tyr Lys Thr Leu Arg Gln Ile Arg Gln Gly Asn Thr
565 570 575
Lys Gln Arg Ile Asp Glu Phe Glu Ala Leu
580 585
Claims (3)
1.定量检测蛋白质EZR的T567位点的磷酸化水平的试剂在制备特发性膜性肾病诊断试剂中的应用。
2.根据权利要求1所述的应用,其特征在于,所述试剂包括蛋白质EZR的T567位点的磷酸化抗体。
3.根据权利要求1所述的应用,其特征在于,所述蛋白质EZR来源于活体肾组织。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111107560.3A CN113899908B (zh) | 2021-09-22 | 2021-09-22 | 磷酸化蛋白质在膜性肾病中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111107560.3A CN113899908B (zh) | 2021-09-22 | 2021-09-22 | 磷酸化蛋白质在膜性肾病中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113899908A CN113899908A (zh) | 2022-01-07 |
CN113899908B true CN113899908B (zh) | 2024-05-28 |
Family
ID=79029123
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111107560.3A Active CN113899908B (zh) | 2021-09-22 | 2021-09-22 | 磷酸化蛋白质在膜性肾病中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113899908B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011037970A1 (en) * | 2009-09-22 | 2011-03-31 | University Of Miami | Podocyte ph modulation and uses thereof |
CN102343091A (zh) * | 2011-03-01 | 2012-02-08 | 中国科学技术大学 | 一种基于ezrin磷酸化的物质及其应用 |
WO2012102963A1 (en) * | 2011-01-26 | 2012-08-02 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Urine biomarkers for prediction of recovery after acute kidney injury : proteomics |
CN104762369A (zh) * | 2014-01-02 | 2015-07-08 | 李子龙 | 确定急性高血压肾损伤时足细胞骨架蛋白及其标志蛋白变化的方法 |
EP3373008A1 (en) * | 2017-03-07 | 2018-09-12 | Pad 4 Di Emanuele Ghiggeri S.A.S. | In vitro method and kit for predicting clinical outcome in patients with membranous nephropathy |
-
2021
- 2021-09-22 CN CN202111107560.3A patent/CN113899908B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011037970A1 (en) * | 2009-09-22 | 2011-03-31 | University Of Miami | Podocyte ph modulation and uses thereof |
WO2012102963A1 (en) * | 2011-01-26 | 2012-08-02 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Urine biomarkers for prediction of recovery after acute kidney injury : proteomics |
CN102343091A (zh) * | 2011-03-01 | 2012-02-08 | 中国科学技术大学 | 一种基于ezrin磷酸化的物质及其应用 |
CN104762369A (zh) * | 2014-01-02 | 2015-07-08 | 李子龙 | 确定急性高血压肾损伤时足细胞骨架蛋白及其标志蛋白变化的方法 |
EP3373008A1 (en) * | 2017-03-07 | 2018-09-12 | Pad 4 Di Emanuele Ghiggeri S.A.S. | In vitro method and kit for predicting clinical outcome in patients with membranous nephropathy |
Non-Patent Citations (6)
Title |
---|
Atypical protein kinase C(iota) activates ezrin in the apical domain of intestinal epithelial cells;Wald et al.;《Journal of cell science》;20080301;第121卷(第Pt5期);第644-654页 * |
Debasis Pore et al..The ezrin-radixin-moesin family of proteins in the regulation of B-cell immune response.《Critical reviews in immunology》.第35卷(第1期),第15-31页. * |
Ezrin及WT1在原发性膜性肾病肾小球的表达及意义;郭嘉鸿;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20080301;2009年(第01期);E067-10第1-59页 * |
Immunopathogenesis of membranous nephropathy:an update;Debiec et al.;《Seminars in immunopathology》;20140409;第36卷;第381-397页 * |
Lable-free quantitative proteomic and phosphoproteomic analyses of renal biopsy tissue in membranous nephropathy;Shanshan Li et al.;《Proteomics. Clinical application》;20220131;第16卷(第1期);文章号e200069 * |
Regulation of Ste20-like kinase, SLK, activity: dimerization and activation segment phosphorylation;Cybulsky et al.;《Plos one》;20170505;第12卷(第5期);文章号e0177226第1-25页 * |
Also Published As
Publication number | Publication date |
---|---|
CN113899908A (zh) | 2022-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Baharlou et al. | Mass cytometry imaging for the study of human diseases—applications and data analysis strategies | |
Sethi et al. | Semaphorin 3B–associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients | |
CN108957011B (zh) | 与妊娠期糖尿病辅助早期诊断相关的血清/血浆多肽标志物及其应用 | |
Liu et al. | Inhibitive effect of Cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism | |
Lee et al. | Subcellular tissue proteomics of hepatocellular carcinoma for molecular signature discovery | |
Wang et al. | Flightless I homolog negatively modulates the TLR pathway | |
WO2022012280A1 (zh) | 一种肺癌的外周血tcr标志物及其检测试剂盒和应用 | |
KR102067327B1 (ko) | 최적의 암 치료를 위한 Her2 단백질 정량 | |
US8834873B2 (en) | Method for detecting and controlling cancer | |
US20150005264A1 (en) | Predictive biomarker for hypoxia-activated prodrug therapy | |
Leprieur et al. | Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression | |
JP2019058171A (ja) | Pd−l1に対するsrmアッセイ | |
Basolo et al. | Histological pattern and gene expression profiling of thyroid tissue in subjects with obesity | |
CN110106244A (zh) | 一种乳腺癌无创分子分型试剂盒及方法 | |
Nie et al. | DIA-based proteomics analysis of serum-derived exosomal proteins as potential candidate biomarkers for intrahepatic cholestasis in pregnancy | |
US10928398B2 (en) | Method for double staining colocalized nuclear-markers in histological lymphoid or bone marrow tissue sample | |
CN113899908B (zh) | 磷酸化蛋白质在膜性肾病中的应用 | |
Kim et al. | Urine SERPINC1/ORM1 as biomarkers for early detection of lupus nephritis in MRL-lpr mice | |
Donato et al. | Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers | |
US10732184B2 (en) | Diagnosis of cancer by detecting auto-antibodies against PAR1 | |
Anil et al. | Bone marrow fibrosis is associated with non‐response to CD19 CAR T‐cell therapy in B‐acute lymphoblastic leukemia | |
CN101575646A (zh) | 合胞素基因在血液系统恶性肿瘤中的应用 | |
Bojazyah | Comparative proteomic analysis of differentially expressed proteins in metastatic breast cancer cell lines in response to oral hypoglycemic treatment | |
Bibas et al. | Waldenström Macroglobulinemia-A State-of-the-Art Review: Part 1: Epidemiology, pathogenesis, clinicopathologic characteristics, differential diagnosis, risk stratification, and clinical problems | |
KR20220149336A (ko) | 부인암 pdx 모델에 대한 성공 예측 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |