Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif re...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Yap, Beow Keat [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2016 |
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| Rechteinformationen: |
Nutzungsrecht: © 2016 Federation of European Biochemical Societies © 2016 Federation of European Biochemical Societies. |
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| Schlagwörter: |
SPRY domain of the SOCS‐box protein 2 |
|---|
| Übergeordnetes Werk: |
Enthalten in: FEBS letters - Amsterdam [u.a.] : Elsevier, 1968, 590(2016), 6, Seite 696-704 |
|---|---|
| Übergeordnetes Werk: |
volume:590 ; year:2016 ; number:6 ; pages:696-704 |
| Links: |
|---|
| DOI / URN: |
10.1002/1873-3468.12115 |
|---|
| Katalog-ID: |
OLC1972729101 |
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| 520 | |a SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. | ||
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| 700 | 1 | |a Harjani, Jitendra R |4 oth | |
| 700 | 1 | |a Leung, Eleanor W. W |4 oth | |
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| 700 | 1 | |a Thompson, Philip E |4 oth | |
| 700 | 1 | |a Baell, Jonathan B |4 oth | |
| 700 | 1 | |a Norton, Raymond S |4 oth | |
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10.1002/1873-3468.12115 doi PQ20160430 (DE-627)OLC1972729101 (DE-599)GBVOLC1972729101 (PRQ)p945-f90075833ab2309781ec27d178ac88fa11e7d7fbbf5f9bb7b93af6b6421bb52a0 (KEY)0045922420160000590000600696redoxstablecyclicpeptideinhibitorsofthespsb2inosin DE-627 ger DE-627 rakwb eng 570 530 610 DNB Yap, Beow Keat verfasserin aut Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. Nutzungsrecht: © 2016 Federation of European Biochemical Societies © 2016 Federation of European Biochemical Societies. anti‐infective SPRY domain of the SOCS‐box protein 2 inducible nitric oxide synthase cyclic peptide redox‐stable Harjani, Jitendra R oth Leung, Eleanor W. W oth Nicholson, Sandra E oth Scanlon, Martin J oth Chalmers, David K oth Thompson, Philip E oth Baell, Jonathan B oth Norton, Raymond S oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 590(2016), 6, Seite 696-704 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:590 year:2016 number:6 pages:696-704 http://dx.doi.org/10.1002/1873-3468.12115 Volltext http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12115/abstract http://www.ncbi.nlm.nih.gov/pubmed/26921848 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 AR 590 2016 6 696-704 |
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10.1002/1873-3468.12115 doi PQ20160430 (DE-627)OLC1972729101 (DE-599)GBVOLC1972729101 (PRQ)p945-f90075833ab2309781ec27d178ac88fa11e7d7fbbf5f9bb7b93af6b6421bb52a0 (KEY)0045922420160000590000600696redoxstablecyclicpeptideinhibitorsofthespsb2inosin DE-627 ger DE-627 rakwb eng 570 530 610 DNB Yap, Beow Keat verfasserin aut Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. Nutzungsrecht: © 2016 Federation of European Biochemical Societies © 2016 Federation of European Biochemical Societies. anti‐infective SPRY domain of the SOCS‐box protein 2 inducible nitric oxide synthase cyclic peptide redox‐stable Harjani, Jitendra R oth Leung, Eleanor W. W oth Nicholson, Sandra E oth Scanlon, Martin J oth Chalmers, David K oth Thompson, Philip E oth Baell, Jonathan B oth Norton, Raymond S oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 590(2016), 6, Seite 696-704 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:590 year:2016 number:6 pages:696-704 http://dx.doi.org/10.1002/1873-3468.12115 Volltext http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12115/abstract http://www.ncbi.nlm.nih.gov/pubmed/26921848 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 AR 590 2016 6 696-704 |
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10.1002/1873-3468.12115 doi PQ20160430 (DE-627)OLC1972729101 (DE-599)GBVOLC1972729101 (PRQ)p945-f90075833ab2309781ec27d178ac88fa11e7d7fbbf5f9bb7b93af6b6421bb52a0 (KEY)0045922420160000590000600696redoxstablecyclicpeptideinhibitorsofthespsb2inosin DE-627 ger DE-627 rakwb eng 570 530 610 DNB Yap, Beow Keat verfasserin aut Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. Nutzungsrecht: © 2016 Federation of European Biochemical Societies © 2016 Federation of European Biochemical Societies. anti‐infective SPRY domain of the SOCS‐box protein 2 inducible nitric oxide synthase cyclic peptide redox‐stable Harjani, Jitendra R oth Leung, Eleanor W. W oth Nicholson, Sandra E oth Scanlon, Martin J oth Chalmers, David K oth Thompson, Philip E oth Baell, Jonathan B oth Norton, Raymond S oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 590(2016), 6, Seite 696-704 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:590 year:2016 number:6 pages:696-704 http://dx.doi.org/10.1002/1873-3468.12115 Volltext http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12115/abstract http://www.ncbi.nlm.nih.gov/pubmed/26921848 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 AR 590 2016 6 696-704 |
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anti‐infective SPRY domain of the SOCS‐box protein 2 inducible nitric oxide synthase cyclic peptide redox‐stable |
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Yap, Beow Keat @@aut@@ Harjani, Jitendra R @@oth@@ Leung, Eleanor W. W @@oth@@ Nicholson, Sandra E @@oth@@ Scanlon, Martin J @@oth@@ Chalmers, David K @@oth@@ Thompson, Philip E @@oth@@ Baell, Jonathan B @@oth@@ Norton, Raymond S @@oth@@ |
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Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction |
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Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction |
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Yap, Beow Keat |
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redox‐stable cyclic peptide inhibitors of the spsb2–inos interaction |
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Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction |
| abstract |
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. |
| abstractGer |
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. |
| abstract_unstemmed |
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2–iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox‐stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full‐length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox‐stable, potent ligands for SPSB proteins as a potential novel class of anti‐infectives. |
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Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction |
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http://dx.doi.org/10.1002/1873-3468.12115 http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12115/abstract http://www.ncbi.nlm.nih.gov/pubmed/26921848 |
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Harjani, Jitendra R Leung, Eleanor W. W Nicholson, Sandra E Scanlon, Martin J Chalmers, David K Thompson, Philip E Baell, Jonathan B Norton, Raymond S |
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Harjani, Jitendra R Leung, Eleanor W. W Nicholson, Sandra E Scanlon, Martin J Chalmers, David K Thompson, Philip E Baell, Jonathan B Norton, Raymond S |
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