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This study determined the effect of alanine mutations on the secondary structure and bioactivity of lyp1987 (GRLQAFLAKMKEIAAQTL\u2010NH<jats:sub>2<\/jats:sub>), a cationic \u03b1\u2010helical AMP obtained from the venom of <jats:italic>Lycosa poonaensis<\/jats:italic> which exhibits broad range activity against Gram\u2010positive and Gram\u2010negative bacteria with micromolar minimum inhibitory concentrations (MIC). CD spectroscopy revealed no significant difference in the secondary structure, with all alanine\u2010substituted analogs exhibiting predominantly \u03b1\u2010helical structure in buffered 2,2,2\u2010trifluoroethanol solution. Alanine substitution at Glu12 and Thr17 increased the activity of lyp1987 against Gram\u2010positive and \u2010negative bacteria, while alanine substitution at Lys9 increased its selectivity against Gram\u2010positive bacteria. Further investigation can be done to determine positions and substitutions that will give less cytotoxic analogs.<\/jats:p>","DOI":"10.1002\/cmdc.202400488","type":"journal-article","created":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T22:15:16Z","timestamp":1723414516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Wheel of Fortune: Helical Wheel Alanine Scanning of a Spider Venom Antimicrobial Peptide Reveals Residues Involved in Antimicrobial and Cytotoxic Activity"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8300-1039","authenticated-orcid":false,"given":"Jomari C.","family":"Fernando","sequence":"first","affiliation":[{"name":"Institute of Chemistry College of Science University of the Philippines Diliman  Quezon City, Metro Manila 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