{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:45:51Z","timestamp":1790423151541,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T00:00:00Z","timestamp":1330905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>The emergence of strains of multidrug\u2010resistant Gram\u2010negative bacteria mandates a search for new types of antimicrobial agents. Alyteserin\u20102a (ILGKLLSTAAGLLSNL.NH<jats:sub>2<\/jats:sub>) is a cationic, <jats:italic>\u03b1<\/jats:italic>\u2010helical peptide, first isolated from skin secretions of the midwife toad, <jats:italic>Alytes obstetricans<\/jats:italic>, which displays relatively weak antimicrobial and haemolytic activities. Increasing the cationicity of alyteserin\u20102a while maintaining amphipathicity by the substitution Gly<jats:sup>11<\/jats:sup>\u2192\u2009Lys enhanced the potency against both Gram\u2010negative and Gram\u2010positive bacteria by between fourfold and 16\u2010fold but concomitantly increased cytotoxic activity against human erythrocytes by sixfold (mean concentration of peptide producing 50% cell death; LC<jats:sub>50<\/jats:sub>\u2009=\u200924\u2009\u00b5<jats:sc>m<\/jats:sc>). Antimicrobial potency was increased further by the additional substitution Ser<jats:sup>7<\/jats:sup>\u2192Lys, but the resulting analogue remained cytotoxic to erythrocytes (LC<jats:sub>50<\/jats:sub>\u2009=\u200938\u2009\u00b5<jats:sc>m<\/jats:sc>). However, the peptide containing <jats:sc>d<\/jats:sc>\u2010lysine at positions 7 and 11 showed high potency against a range of Gram\u2010negative bacteria, including multidrug\u2010resistant strains of <jats:italic>Acinetobacter baumannii<\/jats:italic> and <jats:italic>Stenotrophomonas maltophilia<\/jats:italic> (minimum inhibitory concentration\u2009=\u20098\u2009\u00b5<jats:sc>m<\/jats:sc>) but appreciably lower haemolytic activity (LC<jats:sub>50<\/jats:sub>\u2009=\u2009185\u2009\u00b5<jats:sc>m<\/jats:sc>) and cytotoxicity against A549 human alveolar basal epithelial cells (LC<jats:sub>50<\/jats:sub>\u2009=\u200965\u2009\u00b5<jats:sc>m<\/jats:sc>). The analogue shows potential for treatment of nosocomial pulmonary infections caused by bacteria that have developed resistance to commonly used antibiotics. Copyright \u00a9 2012 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.2397","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T04:17:36Z","timestamp":1331007456000},"page":"270-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Analogues of the frog skin peptide alyteserin\u20102a with enhanced antimicrobial activities against Gram\u2010negative bacteria"],"prefix":"10.1002","volume":"18","author":[{"given":"J. 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