Design of Potent and Salt-Insensitive Antimicrobial Branched Peptides

Abstract

Dendrimeric and branched peptides are polypeptides formed by diverse types of scaffolds to give them different forms. Previously, we reported a cascade-type, Lys-scaffolded antimicrobial peptide dendrimer D4R tethered with four RLYR tetrapeptides. Antimicrobial D4R is broad-spectrum, salt insensitive, and as potent as the natural-occurring tachyplesins, displaying minimum inhibitory concentrations (MIC) 500 μM. Structure-activity relationship studies suggested that Lys-scaffolds, but not Orn-scaffolds, can support a reverse turn to organize RLYR tetrapeptides as parallel β-strands to form an amphipathic structure with Leu-Tyr as a hydrophobic core. Together, these results provide a structural approach for designing potent and salt-insensitive dendrimeric or branched peptide antimicrobials.

Keywords

• peptide dendrimers
• antimicrobial peptides
• polymeric scaffolds
• branched peptides
• isolysine scaffold
• lysine reverse turns