Novel Synthetic Strategies Towards Analogues of Cadaside and Malacidin Antibiotic Peptides

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With antibiotic resistance becoming an increasingly pressing issue, the search for novel antimicrobial drugs is more important than ever before. The recently discovered calcium-dependent lipopeptides cadaside A/B and malacidin A/B have promising activity against resistant Gram-positive bacteria. With limited reports of synthetic routes towards these peptides available in the literature, especially for cadasides, we herein report a novel on-resin synthesis strategy. We used this strategy to produce fifteen simplified malacidin and cadaside analogues. In addition, both minimum inhibitory concentration and thin layer chromatography assays were conducted to determine antimicrobial activity and advance our understanding of these peptides' structure-activity relationships.

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