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In this study, five IsCT1 (ILGKIWEGIKSLF)\u2010based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out.<\/jats:p><jats:p>Peptides with a substitution at position 3 or 5 ([L]<jats:sup>3<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>, [K]<jats:sup>3<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>, or [F]<jats:sup>5<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>) showed no significant change in an activity relative to IsCT1\u2010NH<jats:sub>2<\/jats:sub>. The addition of a proline residue at position 8 ([P]<jats:sup>8<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13\u201050 \u03bcmol L<jats:sup>\u22121<\/jats:sup>), and the addition of a tryptophan residue at position 1 ([W]<jats:sup>1<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>) increased the hemolytic activity (MHC = 1.56 \u03bcmol L<jats:sup>\u22121<\/jats:sup>) without an improvement in antimicrobial activity. The analog [A]<jats:sup>1<\/jats:sup>[F]<jats:sup>5<\/jats:sup>[K]<jats:sup>8<\/jats:sup>\u2010IsCT1\u2010NH<jats:sub>2<\/jats:sub>, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 \u03bcmol L<jats:sup>\u22121<\/jats:sup>) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.<\/jats:p>","DOI":"10.1002\/psc.3219","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T06:44:55Z","timestamp":1571813095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["IsCT\u2010based analogs intending better biological activity"],"prefix":"10.1002","volume":"25","author":[{"given":"Isabel Cristina Chica","family":"Acevedo","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas Universidade Federal do ABC  Santo Andr\u00e9 SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro Ismael","family":"Silva Jr","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Toxinologia Aplicada Instituto Butantan  S\u00e3o Paulo SP 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