Macromolecular assembly and membrane activity of antimicrobial D, L-alpha-Cyclic peptides

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Claro, B (Author) Other; Peon, A (Author) Other; Gonzalez Freire, E (Author) Other; Goormaghtigh, E (Author) Other; Amorin, M (Author) Other; Granja, JR (Author) Other; Garcia Fandino, R (Author) Other; Bastos, M (Author) FCUP

Journal

Title: Colloids and Surfaces B: Biointerfaces

Vol. 208

ISSN: 0927-7765

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00V-B3N

DOI: 10.1016/j.colsurfb.2021.112086

Abstract (EN): Antimicrobial peptides are viewed as a promising alternative to conventional antibiotics, as their activity through membrane targeting makes them less prone to resistance development. Among them, antimicrobial D,L-alpha-cyclic peptides (CPs) have been proposed as an alternative, specially due to their cyclic nature and to the presence of D-alpha-amino acids that increases their resistance to proteases. In present work, second generation D,L-alpha-cyclic peptides with proven antimicrobial activity are shown to form complex macromolecular assemblies in the presence of membranes. We addressed the CPs:membrane interactions through a combination of experimental techniques (DSC and ATR-FTIR) with coarse-grained molecular dynamics (CG-MD) simulations, aiming at understanding their interactions, macromolecular assemblies and eventually unveil their mechanism of action. DSC shows that the interaction depends heavily on the negatively charge content of the membrane and on lipid/peptide ratio, suggesting different mechanisms for the different peptides and lipid systems. CG-MD proved that CPs can self-assemble at the lipid surface as nanotubes or micellar aggregates, depending on the peptide, in agreement with ATR-FTIR results. Finally, our results shed light into possible mechanisms of action of the peptides with pending hydrocarbon tail, namely membrane extensive segregation and/or membrane disintegration through the formation of disk-like lipid/peptide aggregates.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10