N-Capping Effects of Stapled Heptapeptides on Antimicrobial and Hemolytic Activities

Abstract

In our previous study, we showcased the potential of an all-hydrocarbon stapled heptapeptide as a privileged scaffold for the design of artificial antimicrobial peptides. We demonstrated that the amphipathic helicity and the subtle balance between hydrophobicity and hydrophilicity are important structural features for the antimicrobial activities of this class of antimicrobial agents. In this study, we show that elimination of the N-acetyl cap can further improve the pharmacological properties of the most potent stapled heptapeptides. The structure-activity relationships newly established in this study would serve as a critical asset for the further development of a new class of antimicrobial agents to combat the rising problem of antibiotic resistance.