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The advantage of these peptides lies in their ability to simultaneously target both the amyloid cascade hypothesis and the microbial infection hypothesis, in contrast to single\u2010function inhibitors. However, most of the reported dual\u2010functional peptides to date are natural peptides, and the development of synthetic peptides in this area remains limited. In this study, we propose two strategies to aid in the discovery of synthetic dual\u2010functional peptides. We then report four distinct synthetic dual\u2010functional peptides identified using these strategies, with the A\u03b2<jats:sub>1\u201340<\/jats:sub>\/A\u03b2<jats:sub>1\u201342<\/jats:sub> fibrillation system and common bacterial strains serving as a proof\u2010of\u2010concept platform. One strategy involves repurposing existing knowledge, while the other breaks from established conventions. Using the first strategy, we discovered a very short dual\u2010functional linear peptide. With the second strategy, we identified a simple dual\u2010functional cyclic peptide. Furthermore, by combining these two strategies, we developed a hybrid dual\u2010functional peptide incorporating both linear and cyclic structures. We hope that our findings will contribute to the future discovery of more synthetic dual\u2010functional peptides for treating Alzheimer's disease.<\/jats:p>","DOI":"10.1002\/chem.202404349","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:59:44Z","timestamp":1739264384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual\u2010Functional Synthetic Linear and Cyclic Peptides with Anti\u2010Amyloid and Antimicrobial Activities for Alzheimer's Disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Lujuan","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, College 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