Assay platform for clinically relevant metallo-β-lactamases.
Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797053596127199232 |
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| author | van Berkel, S Brem, J Rydzik, A Salimraj, R Cain, R Verma, A Owens, R Fishwick, C Spencer, J Schofield, C |
| author_facet | van Berkel, S Brem, J Rydzik, A Salimraj, R Cain, R Verma, A Owens, R Fishwick, C Spencer, J Schofield, C |
| author_sort | van Berkel, S |
| collection | OXFORD |
| description | Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors. |
| first_indexed | 2024-03-06T18:45:52Z |
| format | Journal article |
| id | oxford-uuid:0e7f5e33-9422-4351-9f2d-f246c85fd211 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:45:52Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:0e7f5e33-9422-4351-9f2d-f246c85fd2112022-03-26T09:46:11ZAssay platform for clinically relevant metallo-β-lactamases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0e7f5e33-9422-4351-9f2d-f246c85fd211EnglishSymplectic Elements at Oxford2013van Berkel, SBrem, JRydzik, ASalimraj, RCain, RVerma, AOwens, RFishwick, CSpencer, JSchofield, CMetallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors. |
| spellingShingle | van Berkel, S Brem, J Rydzik, A Salimraj, R Cain, R Verma, A Owens, R Fishwick, C Spencer, J Schofield, C Assay platform for clinically relevant metallo-β-lactamases. |
| title | Assay platform for clinically relevant metallo-β-lactamases. |
| title_full | Assay platform for clinically relevant metallo-β-lactamases. |
| title_fullStr | Assay platform for clinically relevant metallo-β-lactamases. |
| title_full_unstemmed | Assay platform for clinically relevant metallo-β-lactamases. |
| title_short | Assay platform for clinically relevant metallo-β-lactamases. |
| title_sort | assay platform for clinically relevant metallo β lactamases |
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