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Di\u2010<jats:italic>N<\/jats:italic>\u2010methylation of cationic amphiphiles derived from several diversely structured AGs resulted in a significant increase in hydrophobicity compared to the parent compounds that improved their interactions with membrane lipids. The modification led to an enhancement in antibacterial activity and a broader antimicrobial spectrum. While the parent compounds were either modestly active or inactive against Gram\u2010negative pathogens, the corresponding di\u2010<jats:italic>N<\/jats:italic>\u2010methylated compounds were potent against the tested Gram\u2010negative as well as Gram\u2010positive bacterial strains. The reported modification offers a robust strategy for the development of broad\u2010spectrum membrane\u2010disrupting antibiotics for topical use.<\/jats:p>","DOI":"10.1002\/anie.201506814","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T13:15:56Z","timestamp":1443532556000},"page":"13617-13621","source":"Crossref","is-referenced-by-count":37,"title":["Di\u2010<i>N<\/i>\u2010Methylation of Anti\u2010Gram\u2010Positive Aminoglycoside\u2010Derived Membrane Disruptors Improves Antimicrobial Potency and Broadens Spectrum to Gram\u2010Negative Bacteria"],"prefix":"10.1002","volume":"54","author":[{"given":"Raphael I.","family":"Benhamou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pazit","family":"Shaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido M.","family":"Herzog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha","family":"Fridman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,29]]},"reference":[{"key":"e_1_2_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2474"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1267"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/429323"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)80051-7"},{"key":"e_1_2_3_5_2","first-page":"1","volume":"8","author":"Velkov T.","year":"2014","journal-title":"Future Microbiol."},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500080r"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja964290o"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm1000437"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm401148j"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b00248"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200761"},{"key":"e_1_2_3_11_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200761"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.03.046"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201406404"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00229-15"},{"key":"e_1_2_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201500598"},{"key":"e_1_2_3_15_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201500598"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.16.8856"},{"key":"e_1_2_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02536-13"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.01.014"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.521"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.2174\/1386207043328832"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanie.201506814","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201506814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:47:38Z","timestamp":1697503658000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.201506814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,29]]},"references-count":22,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2015,11,9]]}},"alternative-id":["10.1002\/anie.201506814"],"URL":"https:\/\/doi.org\/10.1002\/anie.201506814","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,29]]}}}