Hydrophobic interactions govern specificity for natural antimicrobial peptides. No such relationship has been established for synthetic peptoids that mimic antimicrobial peptides. Peptoid macrocycles synthesized with five different aromatic groups are investigated by minimum inhibitory and hemolytic concentration assays, epifluorescence microscopy, atomic force microscopy, and X-ray reflectivity. Peptoid hydrophobicity is determined using high performance liquid chromatography. Disruption of bacterial but not eukaryotic lipid membranes is demonstrated on the solid supported lipid bilayers and Langmuir monolayers. X-ray reflectivity studies demonstrate that intercalation of peptoids with zwitterionic or negatively charged lipid membranes is found to be regulated by hydrophobicity. Critical levels of peptoid selectivity are demonstrated and found to be modulated by their hydrophobic groups. It is suggested that peptoids may follow different optimization schemes as compared to their natural analogues.
Konstantin Andreev 1, Michael W. Martynowycz1,3, Mia L. Huang2, Ivan Kuzmenko3, Wei Bu4, Kent Kirshenbaum2, and David Gidalevitz1
1Department of Physics, Center for Molecular Study of Condensed Soft Matter (μCoSM), Pritzker Institute of Biomedical Science and Engineering, Illinois Institute of Technology, 3440 South Dearborn Street, Chicago, IL 60616, United States
2Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, United States
3Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439, United States
4The Center for Advanced Radiation Sources (CARS), University of Chicago, Chicago, IL 60637, United States
BBA – Biomembranes, 1860, p 1414-1423, 2018