{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["d'Andrea FB"],"funding":["Johns Hopkins University","NIAID NIH HHS","National Institutes of Health"],"pagination":["878-884.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6897304"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(6)"],"pubmed_abstract":["Diphenylphosphonates (DPPs) have been used for 50 years to inactivate serine hydrolases, creating adducts representative of tetrahedral intermediates of this important class of enzymes. Failure to react at active site serine residues, however, can thwart their usefulness. Here, we describe a facile route and allied mechanistic studies to highly reactive, structurally complex organofluorophosphonates (FPs) by direct fluorinative hydrolysis of DPPs. Advantages over current preparations of FPs are exemplified by the synthesis of a β-lactam-containing peptide substrate analog capable of modifying the C-terminal, dual-function thioesterase involved in nocardicin A biosynthesis. Although this serine hydrolase was found to resist modification by classic DPP inhibitors, active site selective phosp"],"journal":["Cell chemical biology"],"pubmed_title":["Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases."],"pmcid":["PMC6897304"],"funding_grant_id":["R01 AI014937","AI121072","R01 AI121072"],"pubmed_authors":["Townsend CA","d'Andrea FB"],"additional_accession":[]},"is_claimable":false,"name":"Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.","description":"Diphenylphosphonates (DPPs) have been used for 50 years to inactivate serine hydrolases, creating adducts representative of tetrahedral intermediates of this important class of enzymes. Failure to react at active site serine residues, however, can thwart their usefulness. Here, we describe a facile route and allied mechanistic studies to highly reactive, structurally complex organofluorophosphonates (FPs) by direct fluorinative hydrolysis of DPPs. Advantages over current preparations of FPs are exemplified by the synthesis of a β-lactam-containing peptide substrate analog capable of modifying the C-terminal, dual-function thioesterase involved in nocardicin A biosynthesis. Although this serine hydrolase was found to resist modification by classic DPP inhibitors, active site selective phosp","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2025-04-25T18:43:33.359Z","creation":"2020-10-29T13:17:11Z"},"accession":"S-EPMC6897304","cross_references":{"pubmed":["30982751"],"doi":["10.1016/j.chembiol.2019.02.020"]}}