A Comparative Study on Interactions of Antimicrobial Peptides L- and D-phenylseptin with 1,2-dimyristoyl-sn-glycero-3-phosphocholine

Abstract

L-phenylseptin (L-Phes) and D-phenylseptin (D-Phes) are amphibian antimicrobial peptides isolated from the skin secretion of Hypsiboas punctatus. In the N-termini, L-Phes and D-Phes contain three consecutive phenylalanine residues, l-Phe-l-Phe-l-Phe and l-Phe-d-Phe-l-Phe, respectively. They are known to exhibit antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Xanthomonas axonopodis pv. Glycines. However, their mechanism of action and the role of the D-amino acid residue have not been elucidated yet. In this study, the interactions of both peptides with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were investigated by means of quartz crystal microbalance, circular dichroism, vibrational circular dichroism, 31P solid-state NMR, and molecular dynamics simulation. Both peptides have similar binding constants to the DMPC lipid bilayers, in the order of 106 M−1, and form an α-helix structure in the DMPC lipid bilayers. Both the peptides induce similar changes in the dynamics of DMPC lipids. Thus, in spite of the difference in the conformations caused by the chirality at the N-terminus, the peptides showed similar behavior in the membrane-bound state, experimentally and computationally.

Polarimetric Measurements of Surface Chirality Based on Linear and Nonlinear Light Scattering

“…Mostly, VCD measurements involve solution-state samples. Recently, in order to expand its applicability and measure the VCD of different solid samples such as KBr pellets, and films, solid state VCD (SD-VCD) was developed ( Sasaki et al, 2013 ; Mijiddorj et al, 2019 ; Sato and Kawamura, 2020 ). In one of the applications, SD-VCD was used to study the mechanism of chiral recognition on a solid clay surface ( Sato et al, 2018 ).…”

Epimers l- and d-Phenylseptin: How the relative stereochemistry affects the peptide-membrane interactions

“…A recent work describing the interactions between these peptides and DMPC bilayers, identified the higher hydrophobicity of d-Phes as being an important factor for its higher activity. The authors also conclude that the reason for the hydrophobicity difference between the epimers could be related to π interactions between phenylalanine residues, which is favored in d-Phes [29]. However, despite these valuable insights, a more complete description of the structures and modes of interaction of these peptides is needed.…”