How Unnatural Amino Acids in Antimicrobial Peptides Change Interactions with Lipid Model Membranes.

Autor: Mitra S; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Chen MT; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Stedman F; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Hernandez J; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Kumble G; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Kang X; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Zhang C; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Tang G; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Daugherty I; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Liu W; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Ocloo J; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Klucznik KR; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Li AA; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States., Heinrich F; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.; Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States., Deslouches B; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States., Tristram-Nagle S; Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
Jazyk: angličtina
Zdroj: The journal of physical chemistry. B [J Phys Chem B] 2024 Oct 10; Vol. 128 (40), pp. 9772-9784. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1021/acs.jpcb.4c04152
Abstrakt: This study investigates the potential of antimicrobial peptides (AMPs) as alternatives to combat antibiotic resistance, with a focus on two AMPs containing unnatural amino acids (UAAs), E2-53R (16 AAs) and LE-54R (14 AAs). In both peptides, valine is replaced by norvaline (Nva), and tryptophan is replaced by 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). Microbiological studies reveal their potent activity against both Gram-negative (G(-)) and Gram-positive (G(+)) bacteria without any toxicity to eukaryotic cells at test concentrations up to 32 μM. Circular dichroism (CD) spectroscopy indicates that these peptides maintain α-helical structures when interacting with G(-) and G(+) lipid model membranes (LMMs), a feature linked to their efficacy. X-ray diffuse scattering (XDS) demonstrates a softening of G(-), G(+) and eukaryotic (Euk33) LMMs and a nonmonotonic decrease in chain order as a potential determinant for bacterial membrane destabilization. Additionally, XDS finds a significant link between both peptides' interfacial location in G(-) and G(+) LMMs and their efficacy. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Lack of toxicity in eukaryotic cells may be related to their loss of α-helicity and their hydrocarbon location in Euk33 LMMs. Both AMPs with UAAs offer a novel strategy to wipe out antibiotic-resistant strains while maintaining human cells. These findings are compared with previously published data on E2-35, which consists of the natural amino acids arginine, tryptophan, and valine.
Databáze: MEDLINE
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