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These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2\u2032 and 6\u2032 substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated (i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii) in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2\u2032 forms an intramolecular H bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6\u2032-OH substituent is present.<\/jats:p>","DOI":"10.1128\/aac.01326-12","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T06:53:01Z","timestamp":1346827981000},"page":"6104-6108","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Structure-Activity Relationships among the Kanamycin Aminoglycosides: Role of Ring I Hydroxyl and Amino Groups"],"prefix":"10.1128","volume":"56","author":[{"given":"Sumantha","family":"Salian","sequence":"first","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, ETH Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Matt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Akbergenov","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinde","family":"Harish","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, ETH Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Duscha","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno B.","family":"Bernet","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, ETH Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vasella","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, ETH Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westhof","sequence":"additional","affiliation":[{"name":"Architecture et R\u00e9activit\u00e9 de l'ARN, Universit\u00e9 de Strasbourg, Institut de Biologie Mol\u00e9culaire et Cellulaire Centre National de la Recherche Scientifique, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"B\u00f6ttger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00572-10"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.12.3803-3809.1999"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1021\/ja0543144","article-title":"Exploring the use of conformationally locked aminoglycosides as a new strategy to overcome bacterial resistance","volume":"128","author":"Bastida A","year":"2006","unstructured":"BastidaA. 2006. 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