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Thus, modulation of intermolecular interactions offers a feasible way to enhance the potency of existing AMPs. However, a general strategy to achieve this objective has not been established. Here, we demonstrate that the spectrum of activity of Gram\u2010positive\u2010specific self\u2010assembling AMP Fmoc\u2010phenylalanine can be broadened by co\u2010assembly with non\u2010antibiotic Fmoc\u2010glutamic acid. Biophysical assays confirmed that the co\u2010assembled system disrupted bacterial membrane integrity, leading to cell death. The enhanced potency correlated with the reduced mechanical rigidity of the co\u2010assembled hydrogel, as determined by rheological measurements, and molecular dynamics simulations further revealed that heterogeneous non\u2010covalent interactions were detrimental to the fibril stability. These findings suggest that rationally designed co\u2010assembling partners that weaken stabilizing non\u2010covalent interactions can serve as a common strategy to enhance the antibacterial efficacy of existing AMPs.<\/jats:p>","DOI":"10.1002\/mabi.70221","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:12:48Z","timestamp":1784106768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing the Antimicrobial Potency of Self\u2010Assembling Antibiotics by Co\u2010Assembly\u2010Based Aggregation Modulation"],"prefix":"10.1002","volume":"26","author":[{"given":"Bodhisattwa Das","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Biotechnology National Institute of Technology Durgapur A\u2010Zone, Mahatma Gandhi Road Durgapur West Bengal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kuiri","sequence":"additional","affiliation":[{"name":"Department of Biotechnology National Institute of Technology Durgapur A\u2010Zone, Mahatma Gandhi Road Durgapur West Bengal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thangavel","family":"Vijayakanth","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research George S. 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