dc.creator | Monaco, Serena | es |
dc.creator | Ramírez Cárdenas, Jonathan | es |
dc.creator | Carmona Asenjo, Ana Teresa | es |
dc.creator | Robina Ramírez, Inmaculada | es |
dc.creator | Angulo Álvarez, Jesús | es |
dc.date.accessioned | 2022-09-23T17:49:21Z | |
dc.date.available | 2022-09-23T17:49:21Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Monaco, S., Ramírez Cárdenas, J., Carmona Asenjo, A.T., Robina Ramírez, I. y Angulo Álvarez, J. (2022). Inter-Ligand STD NMR: An Efficient 1D NMR Approach to Probe Relative Orientation of Ligands in a Multi-Subsite Protein Binding Pocket. Pharmaceuticals, 15 (8), 1030. | |
dc.identifier.issn | 1424-8247 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137357 | |
dc.description.abstract | In recent years, Saturation Transfer Difference NMR (STD NMR) has been proven to be a powerful and versatile ligand-based NMR technique to elucidate crucial aspects in the investigation of protein-ligand complexes. Novel STD NMR approaches relying on “multi-frequency” irradiation have enabled us to even elucidate specific ligand-amino acid interactions and explore the binding of fragments in previously unknown binding subsites. Exploring multi-subsite protein binding pockets is especially important in Fragment Based Drug Discovery (FBDD) to design leads of increased specificity and efficacy. We hereby propose a novel multi-frequency STD NMR approach based on direct irradiation of one of the ligands in a multi-ligand binding process, to probe the vicinity and explore the relative orientation of fragments in adjacent binding sub-sites, which we called Inter-Ligand STD NMR (IL-STD NMR). We proved its applicability on (i) a standard protein-ligand system commonly used for ligand-observed NMR benchmarking: Naproxen as bound to Bovine Serum Albumin, and (ii) the biologically relevant system of Cholera Toxin Subunit B and two inhibitors adjacently bound within the GM1 binding site. Relative to Inter-Ligand NOE (ILOE), the current state-of-the-art methodology to probe relative orientations of adjacent ligands, IL-STD NMR requires about one tenth of the experimental time and protein consumption, making it a competitive methodology with the potential to be applied in the pharmaceutical industries. | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación PID2019-109395GB-I00 | es |
dc.description.sponsorship | Junta de Andalucía PY20_01176 | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad CTQ2012-31247, CTQ2016-77270-R | es |
dc.format | application/pdf | es |
dc.format.extent | 14 p. | es |
dc.language.iso | eng | es |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es |
dc.relation.ispartof | Pharmaceuticals, 15 (8), 1030. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Fragment Based Drug Discovery | es |
dc.subject | Ligand-based NMR | es |
dc.subject | Multi-frequency STD NMR | es |
dc.subject | Multi-subsite binding pockets | es |
dc.subject | Protein-ligand interactions | es |
dc.subject | Saturation transfer difference NMR | es |
dc.title | Inter-Ligand STD NMR: An Efficient 1D NMR Approach to Probe Relative Orientation of Ligands in a Multi-Subsite Protein Binding Pocket | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | PID2019-109395GB-I00 | es |
dc.relation.projectID | PY20_01176 | es |
dc.relation.projectID | CTQ2012-31247 | es |
dc.relation.projectID | CTQ2016-77270-R | es |
dc.relation.publisherversion | https://doi.org/10.3390/ph15081030 | es |
dc.identifier.doi | 10.3390/ph15081030 | es |
dc.journaltitle | Pharmaceuticals | es |
dc.publication.volumen | 15 | es |
dc.publication.issue | 8 | es |
dc.publication.initialPage | 1030 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | es |