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

Autor: Talita L. Santos, Jarbas M. Resende, Regina Adão, Rodrigo M. Verly, Carolina S. Ferreira, Dorila Piló-Veloso, Mariana T.Q. de Magalhães, Antônio F. C. Alcântara, Lucio O. Nunes, Victor H. O. Munhoz, Burkhard Bechinger, Christopher Aisenbrey
Přispěvatelé: University of Minho [Braga], Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biochimica et Biophysica Acta:Biomembranes
Biochimica et Biophysica Acta:Biomembranes, Elsevier, 2021, 1863 (11), pp.183708. ⟨10.1016/j.bbamem.2021.183708⟩
ISSN: 0005-2736
1879-2642
DOI: 10.1016/j.bbamem.2021.183708⟩
Popis: International audience; Conformational analysis of peptides Biophysical prediction of peptide-membrane interactions Antimicrobial mechanism of action Membrane active peptides L and D peptide epimers ABSTRACT In recent decades, several epimers of peptides containing d-amino acids have been identified in antimicrobial sequences, a feature which has been associated with post-translational modification. Generally, d-isomers present similar or inferior antimicrobial activity, only surpassing their epimers in resistance to peptidases. The naturally occurring l-Phenylseptin (l-Phes) and d-Phenylseptin (d-Phes) peptides (FFFDTLKNLAGKVIGALT-nh 2) were reported with d-epimer showing higher activity against Staphylococcus aureus and Xanthomonas axonopodis in comparison with the l-epimer. In this study, we combine structural (CD, solution NMR), orientational (solid-state NMR) and biophysical (ITC, DSC and DLS) studies to understand the role of the d-phenylalanine in the increase of the antimicrobial activity. Although both peptides are structurally similar in the helical region ranging from D4 to the C-terminus, significant structural differences were observed near the peptides' N-termini (which encompasses the FFF motif). Specific aromatic interactions involving the phenylalanine side chains of d-Phes is responsible to maintaining the F1-F3 residues on the hydrophobic face of the peptide, increasing its amphipathicity when compared to the l-epimer. The higher capability of d-Phes to exert an efficient anchoring in the hydrophobic core of the phospholipid bilayer indicates a pivotal role of the N-terminus in enhancing the interaction between the d-peptide and the membrane interface in relation to its epimer.
Databáze: OpenAIRE
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