The lipidation and glycosylation enabling bioactivity enhancement and structural change of antibacterial peptide G3

Bacterial resistance has led to increased interest in the use of antibacterial peptides (AMPs), but their clinical application is limited by poor stability and solubility, as well as complex cytotoxicity. Chemical modification is a common strategy to modulate AMPs. In this study, a de novo designed AMP (G3) was modified by adding an alkyl acid at the N-terminal and a monosaccharide at the C-terminal. Bio-activity assays demonstrated that conjugation with n-caprylic acid increased the peptide's antibacterial activity and permeabilized the membrane. Attachment of glucose or galactose at the C-terminal improved its biofilm inhibitory capacity and marginally reduced cytotoxicity. The hybrid peptide, containing both n-caprylic acid and galactose, exhibited excellent antibacterial and antibiofilm activity, as well as permeabilized the outer membrane.