{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:03:46Z","timestamp":1792091026618,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI123352"],"award-info":[{"award-number":["AI123352"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We describe the convergent synthesis of a 5\u2010<jats:italic>O<\/jats:italic>\u2010\u03b2\u2010D\u2010ribofuranosyl\u2010based apramycin derivative (apralog) that displays significantly improved antibacterial activity over the parent apramycin against wild\u2010type ESKAPE pathogens. In addition, the new apralog retains excellent antibacterial activity in the presence of the only aminoglycoside modifying enzyme (AAC(3)\u2010IV) acting on the parent, without incurring susceptibility to the APH(3\u2019) mechanism that disables other 5\u2010<jats:italic>O<\/jats:italic>\u2010\u03b2\u2010D\u2010ribofuranosyl 2\u2010deoxystreptamine type aminoglycosides by phosphorylation at the ribose 5\u2010position. Consistent with this antibacterial activity, the new apralog has excellent 30\u2005nM activity (IC<jats:sub>50<\/jats:sub>) for the inhibition of protein synthesis by the bacterial ribosome in a cell\u2010free translation assay, while retaining the excellent across\u2010the\u2010board selectivity of the parent for inhibition of bacterial over eukaryotic ribosomes. Overall, these characteristics translate into excellent in\u2005vivo efficacy against <jats:italic>E. coli<\/jats:italic> in a mouse thigh infection model and reduced ototoxicity vis \u00e0 vis the parent in mouse cochlear explants.<\/jats:p>","DOI":"10.1002\/cmdc.202000726","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T13:20:08Z","timestamp":1601644808000},"page":"335-339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["An Advanced Apralog with Increased in\u2005vitro and in\u2005vivo Activity toward Gram\u2010negative Pathogens and Reduced ex vivo Cochleotoxicity"],"prefix":"10.1002","volume":"16","author":[{"given":"Amr","family":"Sonousi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry Faculty of Pharmacy Cairo University  Cairo 11562 Egypt"},{"name":"Department of Chemistry Wayne State University  5101 Cass Avenue Detroit MI 48202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C. K.","family":"Quirke","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biomedical Sciences and Department of Chemistry and Complex Carbohydrate Research Center University of Georgia  250 West Green Street Athens GA 30602 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabuddha","family":"Waduge","sequence":"additional","affiliation":[{"name":"Department of Chemistry Wayne State University  5101 Cass Avenue Detroit MI 48202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Janusic","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology University of Zurich  Gloriastrasse 28 8006 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Gysin","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology University of Zurich  Gloriastrasse 28 8006 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Haldimann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology University of Zurich  Gloriastrasse 28 8006 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Walton Research Building, Room 403-E  39 Sabin Street Charleston SC 29425 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven N.","family":"Hobbie","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology University of Zurich  Gloriastrasse 28 8006 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Hua","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Walton Research Building, Room 403-E  39 Sabin Street Charleston SC 29425 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schacht","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute Department of Otolaryngology University of Michigan  1150 West Medical Center Drive Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S.","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Chemistry Wayne State University  5101 Cass Avenue Detroit MI 48202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vasella","sequence":"additional","affiliation":[{"name":"Organic Chemistry Laboratory ETH Z\u00fcrich  Vladimir-Prelog-Weg 1\u20135\/10 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"B\u00f6ttger","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology University of Zurich  Gloriastrasse 28 8006 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-0083","authenticated-orcid":false,"given":"David","family":"Crich","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biomedical Sciences and Department of Chemistry and Complex Carbohydrate Research Center University of Georgia  250 West Green Street Athens GA 30602 USA"},{"name":"Department of Chemistry Wayne State University  5101 Cass Avenue Detroit MI 48202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00441"},{"key":"e_1_2_2_3_2","author":"Brennan-Krohn T.","year":"2020","journal-title":"Transl. Res."},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2017.117"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00874a003"},{"key":"e_1_2_2_6_1","unstructured":"\u00a0"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204073109"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/3.6.609"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky546"},{"key":"e_1_2_2_10_2","first-page":"0096","author":"Galani I.","year":"2018","journal-title":"ECCMID"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.09.002"},{"key":"e_1_2_2_12_1","unstructured":"\u00a0"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr0301088"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802610792928040"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5MD00384A"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5MD00344J"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020284"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-1400-1_7"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127218"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176133"},{"key":"e_1_2_2_21_1","unstructured":"\u00a0"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01374-19"},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2016.02.011"},{"key":"e_1_2_2_24_1","unstructured":"\u00a0"},{"key":"e_1_2_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq408"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00001"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00052"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38634-3"},{"key":"e_1_2_2_29_1","unstructured":"https:\/\/www.imi.europa.eu\/projects-results\/project-factsheets\/enable; accessed Feb 12 2019."},{"key":"e_1_2_2_30_1","unstructured":"\u00a0"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402146"},{"key":"e_1_2_2_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b11601"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02275"},{"key":"e_1_2_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2017.03.006"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b12420"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.34.1434"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja972599h"},{"key":"e_1_2_2_38_1","unstructured":"\u00a0"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811258106"},{"key":"e_1_2_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707265105"},{"key":"e_1_2_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm658"},{"key":"e_1_2_2_42_2","first-page":"937861","author":"Huth M. E.","year":"2011","journal-title":"Int. J. Otolaryngol."},{"key":"e_1_2_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0793-289"},{"key":"e_1_2_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2013.01.006"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.2741\/Wright"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200900073"},{"key":"e_1_2_2_47_1","unstructured":"\u00a0"},{"key":"e_1_2_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/327389a0"},{"key":"e_1_2_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2018.10.015"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202000726","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202000726","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202000726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T09:42:17Z","timestamp":1760262137000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202000726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,23]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,1,19]]}},"alternative-id":["10.1002\/cmdc.202000726"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202000726","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,23]]},"assertion":[{"value":"2020-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}