Submonomer Synthesis of Inverse Polyamidoamine (i‐PAMAM) Dendrimer Antibacterials

Abstract

AbstractHerein we report that the submonomer method for peptoid synthesis enables access to pure i‐PAMAM dendrimers up to 16 amino termini by a divergent solid‐phase synthesis using the inexpensive bis(3‐trifluoroacetamidopropyl)amine as branching unit. We exemplify this new and efficient approach by a structure‐activity relationship study of antibacterial dendrimers obtained by appending the polycationic i‐PAMAM dendrimer to a hydrophobic core consisting of either an oligoleucine peptide or an oligo‐N‐isobutylglycine peptoid. These non‐hemolytic dendrimers kill Gram‐negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli as well as the Gram‐positive methicillin‐resistant Staphylococcus aureus (MRSA) by a non‐membrane disruptive mechanism involving aggregation of intracellular content as reported for antimicrobial peptoids.