forapin and Neoplasms

Infections with multidrug-resistant pathogens are an increasing concern for public health. Recently, subtypes of peptide-peptoid hybrids were demonstrated to display potent activity against multidrug-resistant Gram-negative bacteria. Here, structural variation of these antibacterial peptidomimetics was investigated as a tool for optimizing cell selectivity. A protocol based on dimeric building blocks allowed for efficient synthesis of an array of peptide-peptoid oligomers representing length variation as well as different backbone designs displaying chiral or achiral peptoid residues. Lack of α-chirality in the side chains of the peptoid residues proved to be correlated to reduced cytotoxicity. Furthermore, optimization of the length of these peptidomimetics with an alternating cationic-hydrophobic design was a powerful tool to enhance the selectivity against Gram-negative pathogens over benign mammalian cells. Thus, lead compounds with a high selectivity toward killing of clinically important multidrug-resistant E. coli were identified.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Antineoplastic Agents; Cell Proliferation; Circular Dichroism; Drug Resistance, Multiple; Gram-Negative Bacteria; Humans; Liposomes; Microbial Sensitivity Tests; Molecular Structure; Neoplasms; Peptidomimetics; Structure-Activity Relationship; Tumor Cells, Cultured