{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["van Haren MJ"],"funding":["European Research Council"],"pagination":["3806-3811"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7986777"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(11)"],"pubmed_abstract":["The increasing prevalence of metallo-β-lactamase (MBL)-expressing bacteria presents a worrying trend in antibiotic resistance. MBLs rely on active site zinc ions for their hydrolytic activity and the pursuit of MBL-inhibitors has therefore involved the investigation of zinc chelators. To ensure that such chelators specifically target MBLs, a series of cephalosporin prodrugs of two potent zinc-binders: dipicolinic acid (DPA) and 8-thioquinoline (8-TQ) was prepared. Although both DPA and 8-TQ bind free zinc very tightly (K<sub>d</sub> values in the low nm range), the corresponding cephalosporin conjugates do not. The cephalosporin conjugates are efficiently hydrolyzed by MBLs to release DPA or 8-TQ, as confirmed by using both NMR and LC-MS studies. Notably, the cephalosporin prodrugs of DPA "],"journal":["Chemistry (Weinheim an der Bergstrasse, Germany)"],"pubmed_title":["Cephalosporin Prodrug Inhibitors Overcome Metallo-β-Lactamase Driven Antibiotic Resistance."],"pmcid":["PMC7986777"],"funding_grant_id":["ERC consolidator grant (grant agreement no. 725523)","725523"],"pubmed_authors":["Bruchle NC","Tehrani KHME","Wade N","van Haren MJ","Martin NI","Kotsogianni I","Mashayekhi V"],"additional_accession":[]},"is_claimable":false,"name":"Cephalosporin Prodrug Inhibitors Overcome Metallo-β-Lactamase Driven Antibiotic Resistance.","description":"The increasing prevalence of metallo-β-lactamase (MBL)-expressing bacteria presents a worrying trend in antibiotic resistance. MBLs rely on active site zinc ions for their hydrolytic activity and the pursuit of MBL-inhibitors has therefore involved the investigation of zinc chelators. To ensure that such chelators specifically target MBLs, a series of cephalosporin prodrugs of two potent zinc-binders: dipicolinic acid (DPA) and 8-thioquinoline (8-TQ) was prepared. Although both DPA and 8-TQ bind free zinc very tightly (K<sub>d</sub> values in the low nm range), the corresponding cephalosporin conjugates do not. The cephalosporin conjugates are efficiently hydrolyzed by MBLs to release DPA or 8-TQ, as confirmed by using both NMR and LC-MS studies. Notably, the cephalosporin prodrugs of DPA ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Feb","modification":"2025-04-27T01:16:36.204Z","creation":"2025-02-19T00:35:14.325Z"},"accession":"S-EPMC7986777","cross_references":{"pubmed":["33237604"],"doi":["10.1002/chem.202004694"]}}