{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:16Z","timestamp":1791352276780,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Peptidoglycan (PG) is the key structural component of the bacterial cell wall, responsible for cellular shape and structural integrity. Postsynthetic modifications to PG enable bacteria to evade innate immunity and regulate endogenous autolysins. Among these, C\u20106\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetylation protects PG from lysozyme degradation, while\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetylpeptidoglycan esterase (Ape) removes this modification to restore the free C\u20106 hydroxyl group required for lytic transglycosylase activity. Deletion of the\n                    <jats:italic>ape<\/jats:italic>\n                    gene resulted in aberrant cell morphology and attenuated virulence, identifying Ape as a potential antibacterial target. Previously, we reported aldehyde\u2010based competitive inhibitors (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    = 13 \u00b5M) of Ape from\n                    <jats:italic>Campylobacter jejuni<\/jats:italic>\n                    and demonstrated that formation of a covalent hemiacetal adduct, which mimics the tetrahedral intermediate in catalysis, is critical for binding. In this work, we expanded the inhibitor series to examine the contributions of the peptide stem, the anomeric substituent, and the electrophilic carbonyl functionality to Ape inhibition. The synthesized reversible competitive inhibitors exhibited micromolar to submillimolar potency. Peptide stem extension provided little improvement in affinity, while a benzyl substituent at the anomeric position reduced inhibitory potency. Monofluorinated analogues showed modest improvements, whereas difluoroaldehyde and trifluoromethyl ketone derivatives displayed reduced affinity. Finally, irreversible covalent inhibitors bearing dimethylphosphonate and epoxide functionalities proved ineffective against Ape.\n                  <\/jats:p>","DOI":"10.1002\/chem.71774","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:33:18Z","timestamp":1791351198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MurNAc\u2010Based Electrophilic Inhibitors of\n                    <i>O<\/i>\n                    \u2010Acetylpeptidoglycan Esterase (Ape): Design, Synthesis, and Kinetic Evaluation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9738-1409","authenticated-orcid":false,"given":"Dmytro","family":"Voskoboinyk","sequence":"first","affiliation":[{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3224-3491","authenticated-orcid":false,"given":"Martin E.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106976.2007.00094.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00773"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000414"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006512"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106976.2007.00088.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2014.03.010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2025.109517"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010micro\u2010020518\u2010120056"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00277"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106976.2007.00099.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2017.1337705"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02332"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010020\u20100366\u20103"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.108531"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.436352"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi700254m"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1399004714016770"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","unstructured":"C. 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