Casanova, Jannelle R.Villaraza, Aaron Joseph L.Salvador-Reyes, Lilibeth2025-04-122024-03-18Casanova, J. R., Villaraza, A. J. L., & Salvador-Reyes, L. (2024). Synthesis and biological evaluation of cyanobacterial-inspired peptides. <i>Science and Engineering Journal<i>, <i>17</i>(Supplement), 42-88.2799-189X10.54645/202417supjea-58https://hdl.handle.net/20.500.14697/298This study was funded by the Philippine Council for Health Research and Development – Department of Science and Technology through the Discovery and Development of Health Products – Marine Component Program. J.R.C acknowledges scholarship support from the Accelerated Science and Technology Human Resource Development Program of the Department of Science and Technology – Science Education Institute. We acknowledge the assistance of Z. Malto, J. Peran and S. Susana in the conduct of the biological assays. This is MSI Contribution No. 502.Cyanobacteria are known producers of structurally diverse and potent natural products; the majority are peptides with unique modifications. Yet, there remains a huge underexplored chemodiversity from cyanobacteria. Here, we designed a linear octapeptide as a product of combinatorial peptide design inspired by the natural products from the filamentous cyanobacteria <i>Hapalosiphon welwitschii</i> and <i>Leptolyngbya</i> sp. The target peptide was synthesized via solid-phase peptide synthesis (SPPS) using fluorenylmethyloxycarbonyl-protecting group (Fmoc) strategy. Structural diversity was expanded by the substitution of unnatural amino acids to yield five analogues. The structure and sequence of the synthesized peptides were confirmed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Biological activity evaluation was done; with none of the peptides showing antimicrobial or cytotoxic activities against microbial pathogens and mammalian cells, respectively. To our knowledge, this study is the first to report a combinatorial peptide design inspired by a natural product and a predicted biosynthetic product. This strategy of peptide design expands the chemistry of a known bioactive natural product with the aid of unexplored cyanobacterial biosynthetic gene clusters.enCyanobacteriaPeptidesNuclear magnetic resonanceMass spectrometryPeptides--SynthesisArticleSDG 3 - Good health and well-beingSDG 9 - Industry, innovation and infrastructureCyanobacteriapeptidesNMR spectroscopymass spectrometrycytotoxicityChallenge 4: Develop a sustainable and equitable ocean economyChallenge 9: Skills, knowledge, and technology for all