Corannulene\nAmino\nAcid-Derived Water-Soluble Amphiphilic\nBuckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents

To date, the use of corannulene has\nbeen restricted in the area\nof material science, but its application in biomedical research has\nyet to be established due to its nonsolubility in an aqueous environment\nand synthetic infeasibility. Herein, we detail the development of\na new family of highly curved π-conjugated corannulene-containing\nunnatural α-amino acid (CAA) derivatives to overcome this challenge.\nThese CAAs have been extended as novel constituents for the synthesis\nof corannulene-containing water-soluble cationic peptides (CCPs),\nwhich display inhibitory activity against broad-spectrum pathogenic\nbacteria along with drug-resistant bacteria via a membrane-damaging\nmechanism. Importantly, several of the synthesized peptides were found\nto be appreciably nonhemolytic against hRBCs and noncytotoxic against\nmammalian 3T3 cells. <i>In vivo</i> efficacy studies of\nthe potent and least cytotoxic peptide <b>6a</b> demonstrated\nclearance of bacteria from the spleen, liver, lung, and blood of mice\ninfected with <i>S</i>. <i>aureus</i> ATCC 25923.