Inhibitory effects and mechanisms of physiological conditions on the activity of enantiomeric forms of an α-helical antibacterial peptide against bacteria

► In the presence of NaCl, CaCl2 or human serum albumin at physiological concentrations, inhibitory effects of physiological conditions on antimicrobial activity of enantiomeric peptides have been investigated. ► The electrostatic interaction between peptides and biomembrane was inhibited in the presence of salts. ► Salts especially CaCl2 weakened the ability of peptides to permeabilize the outer membrane of Gram-negative bacteria. ► Peptide showed different binding association abilities to HSA at different molar ratios, which is irrelevant to the peptide chirality and caused the reduction of peptide antimicrobial activity. ► d-peptide showed better performance than its l-enantiomer in all tested conditions owing to its resistance against proteolysis, hence, may be a promising candidate as therapeutic in clinical practices.