Biophysical Investigations of Antimicrobial Peptide Mimics for Mechanistic Studies

With a relentless rise in the growth of antimicrobial resistance, much attention is being focused on Antimicrobial peptides (AMP) and the development of AMP mimicking agents to combat this nefarious issue. However lesser reports come up with adequate reasoning behind the driving force of the membrane perturbing nature. Here, we shall be discussing the two branches of AMP mimics, peptoids and small molecules. Further, we explore the mode of action behind the antimicrobial properties displayed by the library of peptoids and small molecule mimics. To address this big challenge of understanding how the membrane active compound behaves, each of the compounds were introduced to the liposomes, mimicking the bacterial model membranes, and their interactions was recorded using solid state nuclear magnetic resonance spectroscopy. We observe that each of the mimics interact with the liposome as the global shape of the vesicles gets deformed. Also we observed a definite interaction with the fatty acyl chain as changes in order parameters were observed with respect to that of pure lipids. To develop a thorough understanding of the pore forming abilities of these compounds, a fluorescent dye release studies was executed using both bacterial and mammalian model membranes. The calcein dye release test revealed that the small molecule mimics undergo a cooperative effect. For the peptoids investigated, the extent of release could be correlated with their antimicrobial activity as well as the toxicity data.