Superior affinity of ubiquicidin peptide united with <i>ortho</i>-borylated acetophenone to an amine-containing model bacterial membrane.

Abstract

Antimicrobial peptides (AMPs) have been considered as potential agents to combat bacterial resistance to conventional antibiotics. It has been shown that modifying the cationic peptides with 2-acetylphenylboronic acid (2-APBA) improves the binding efficacy with these resistant bacterial membranes <i>via</i> the formation of a covalent iminoboronate bond with lipids, such as 1,2-dioleoyl-<i>sn-glycero</i>-3-[phospho-<i>rac</i>-(3-lysyl(1-<i>glycerol</i>))] (Lys PG). In the present study, the cationic peptide UBI (29-41) is modified with 2-APBA at the C-terminus to investigate its affinity to membranes of such lipids. The surface pressure-area isotherm, dilation rheology and atomic force microscopy (AFM) studies are performed on the monolayers formed at the air-water interface by the cationic lipid Lys PG and 1,2-distearoyl-<i>sn-glycero</i>-3-ethylphosphocholine (DSEPC). The modified UBI-2-APBA substantially enhances its membrane affinity compared to the unmodified UBI (29-41). This observation is consistent with covalent bond formation <i>via</i> iminoboronate linkages. However, the cationic lipid Lys PG exhibits an insertion of UBI-2-APBA into the lipid film, whereas DSEPC shows only an adsorption of the peptide. Interestingly, the affinity of both the peptides to zwitterionic lipid 1,2-distearoyl-<i>sn-glycero</i>-3-phosphoethanolamine (DSPE) is found to be similar. Therefore, the findings here indicate the potential of 2-APBA functionalization of peptides as a powerful strategy to selectively target bacterial membranes.