Peptides containing hydrophobic and positively charged residues have been demonstrated to be effective molecular transporters or antimicrobial agents. Herein, we report the synthesis and biological evaluation of a novel series of hybrid peptides containing antimicrobial peptides (AMPs) and/or cell-penetrating peptides (CPPs) containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues. The peptides included [RW]5K-(AH-132), [R4W4]K-(AH-132), and [DipR]5, where AH-132 is a linear antimicrobial peptide. [RW]5 and [R4W4] have been previously reported by us introduced as molecular transporter CPP and antimicrobial agent, respectively. The hybrid peptides were purified by Reverse-Phase HPLC and characterized by MALDI-TOF. Minimum Inhibitory Concentration (MIC) values were determined on the Gram-Negative E. Coli, P. aeruginosa, K. pneumonia, and the Gram-Positive MRSA pathogens and were in the range of 3.1 to 6.2 µg/mL for individual AMPs; while the MIC for the hybrid peptides was &gt;50 µg/mL, suggesting loss of antibacterial activity upon conjugation. The molecular transport capabilities were explored using Green Fluorescent Protein (GFP) as a model protein by confocal microscopy using MDA-MB-231, SK-OV-3, and HEK 293 cell lines. The mean fluorescence intensity (MFI) was calculated for each treatment using ImageJ. In all cases, both hybrid peptides showed significantly higher MFI than their non-hybrid counterparts. The delivery of GFP was dependent on the nature of the peptide and peptide concentration and was significantly improved in the presence of [DipR]5 and hybrid [RW]4K-(AH-132).

Hybrid-amphipathic peptides for enhanced antibacterial activity and protein delivery

ACS Spring 2022

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