1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery
WaterLOGSY is a sensitive ligand-observed NMR experiment for detection of interaction between a ligand and a protein and is now well-established as a screening technique for fragment-based lead discovery. Here we develop and assess a protocol to derive ligand epitope mapping from WaterLOGSY data and...
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| Veröffentlicht in: | Journal of enzyme inhibition and medicinal chemistry 2019-01, Vol.34 (1), p.1218-1225 |
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| container_title | Journal of enzyme inhibition and medicinal chemistry |
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| creator | Raingeval, Claire Cala, Olivier Brion, Béatrice Le Borgne, Marc Hubbard, Roderick Eliot Krimm, Isabelle |
| description | WaterLOGSY is a sensitive ligand-observed NMR experiment for detection of interaction between a ligand and a protein and is now well-established as a screening technique for fragment-based lead discovery. Here we develop and assess a protocol to derive ligand epitope mapping from WaterLOGSY data and demonstrate its general applicability in studies of fragment-sized ligands binding to six different proteins (glycogen phosphorylase, protein peroxiredoxin 5, Bcl-x
L
, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein. |
| doi_str_mv | 10.1080/14756366.2019.1636235 |
| format | Article |
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L
, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein.</description><identifier>ISSN: 1475-6366</identifier><identifier>EISSN: 1475-6374</identifier><identifier>DOI: 10.1080/14756366.2019.1636235</identifier><identifier>PMID: 31286785</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Analytical chemistry ; binding mode ; Binding Sites ; Chemical Sciences ; Drug Discovery - methods ; fragment-based lead discovery ; Magnetic Resonance Spectroscopy - methods ; Medicinal Chemistry ; Proteins - chemistry ; Research Paper ; saturation transfer difference ; solvent-exposed ; WaterLOGSY</subject><ispartof>Journal of enzyme inhibition and medicinal chemistry, 2019-01, Vol.34 (1), p.1218-1225</ispartof><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c634t-57d70e583dab2364fe38b2242ae67d33b5b459124cca54fe56eeab0fcd3436603</citedby><cites>FETCH-LOGICAL-c634t-57d70e583dab2364fe38b2242ae67d33b5b459124cca54fe56eeab0fcd3436603</cites><orcidid>0000-0002-1161-429X ; 0000-0002-8233-7461 ; 0000-0003-3579-0973 ; 0000-0002-5981-109X ; 0000-0003-1398-075X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691826/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691826/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,27501,27923,27924,53790,53792,59142,59143</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31286785$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02188259$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Raingeval, Claire</creatorcontrib><creatorcontrib>Cala, Olivier</creatorcontrib><creatorcontrib>Brion, Béatrice</creatorcontrib><creatorcontrib>Le Borgne, Marc</creatorcontrib><creatorcontrib>Hubbard, Roderick Eliot</creatorcontrib><creatorcontrib>Krimm, Isabelle</creatorcontrib><title>1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery</title><title>Journal of enzyme inhibition and medicinal chemistry</title><addtitle>J Enzyme Inhib Med Chem</addtitle><description>WaterLOGSY is a sensitive ligand-observed NMR experiment for detection of interaction between a ligand and a protein and is now well-established as a screening technique for fragment-based lead discovery. Here we develop and assess a protocol to derive ligand epitope mapping from WaterLOGSY data and demonstrate its general applicability in studies of fragment-sized ligands binding to six different proteins (glycogen phosphorylase, protein peroxiredoxin 5, Bcl-x
L
, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein.</description><subject>Analytical chemistry</subject><subject>binding mode</subject><subject>Binding Sites</subject><subject>Chemical Sciences</subject><subject>Drug Discovery - methods</subject><subject>fragment-based lead discovery</subject><subject>Magnetic Resonance Spectroscopy - methods</subject><subject>Medicinal Chemistry</subject><subject>Proteins - chemistry</subject><subject>Research Paper</subject><subject>saturation transfer difference</subject><subject>solvent-exposed</subject><subject>WaterLOGSY</subject><issn>1475-6366</issn><issn>1475-6374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9kVtv1DAQhSMEohf4CaA8wkMW3-N9QVSl0KIFJC5CPFkTe7ybKolbO7to_z1esl1RHniydebMN5o5RfGMkhklmryiopaKKzVjhM5nNH8Zlw-K451eKV6Lh4e_UkfFSUrXhDDKqHhcHHHKtKq1PC4-0Lflp49fyh8wYlx8fv_1ZwmphKFE71vb4jCWPY6r4EofYukjLPusVQ0kdGWH4ErXJhs2GLdPikceuoRP9-9p8f3dxbfzyypjr87PFpVVXIyVrF1NUGruoGFcCY9cN4wJBqhqx3kjGyHnlAlrQeaqVIjQEG8dF3kVwk-Lq4nrAlybm9j2ELcmQGv-CCEuDcSxtR0a6r0njWC-QSWUtg2gp6B5rdHVUPPMej2xbtZNj87m3SJ096D3K0O7MsuwMUrNqWYqA15OgNU_bZdnC7PT8s21ZnK-odn7Yj8shts1ptH0-XbYdTBgWCfDmBSS5VPU2Sonq40hpYj-wKbE7PI3d_mbXf5mn3_ue_73Poeuu8Cz4c1kaIccaA-_QuycGWHbhZjTHWybsvm_M34DIiW-Sg</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Raingeval, Claire</creator><creator>Cala, Olivier</creator><creator>Brion, Béatrice</creator><creator>Le Borgne, Marc</creator><creator>Hubbard, Roderick Eliot</creator><creator>Krimm, Isabelle</creator><general>Taylor & Francis</general><general>Informa Healthcare</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1161-429X</orcidid><orcidid>https://orcid.org/0000-0002-8233-7461</orcidid><orcidid>https://orcid.org/0000-0003-3579-0973</orcidid><orcidid>https://orcid.org/0000-0002-5981-109X</orcidid><orcidid>https://orcid.org/0000-0003-1398-075X</orcidid></search><sort><creationdate>20190101</creationdate><title>1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery</title><author>Raingeval, Claire ; 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L
, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>31286785</pmid><doi>10.1080/14756366.2019.1636235</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1161-429X</orcidid><orcidid>https://orcid.org/0000-0002-8233-7461</orcidid><orcidid>https://orcid.org/0000-0003-3579-0973</orcidid><orcidid>https://orcid.org/0000-0002-5981-109X</orcidid><orcidid>https://orcid.org/0000-0003-1398-075X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analytical chemistry binding mode Binding Sites Chemical Sciences Drug Discovery - methods fragment-based lead discovery Magnetic Resonance Spectroscopy - methods Medicinal Chemistry Proteins - chemistry Research Paper saturation transfer difference solvent-exposed WaterLOGSY |
| title | 1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery |
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