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This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro\u2010adrenomedullin N\u2010terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an \u03b1\u2010helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C\u2010terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal\u2010isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic \u03b1\u2010helical arrangement with the conserved C\u2010terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences.<\/jats:p>","DOI":"10.1111\/cbdd.14588","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T02:49:15Z","timestamp":1721875755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In silico optimization of analogs derived pro\u2010adrenomedullin peptide to evaluate antimicrobial potential"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-8277","authenticated-orcid":false,"given":"Raquel M.","family":"Quigua\u2010Orozco","sequence":"first","affiliation":[{"name":"S\u2010Inova Biotech, Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Biotecnologia Universidade Cat\u00f3lica Dom Bosco  Campo Grande Mato Grosso do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora E. 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