Partition of antimicrobial D-L-alpha-cyclic peptides into bacterial model membranes

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Claro, B (Author) Other; Gonzalez Freire, E (Author) Other; Granja, JR (Author) Other; Garcia Fandino, R (Author) Other; Gallova, J (Author) Other; Uhrikova, D (Author) Other; Fedorov, A (Author) Other; Coutinho, A (Author) Other; Bastos, M (Author) FCUP

Journal

Title: Biochimica et Biophysica Acta: Biomembranes

Vol. 1864

ISSN: 0005-2736

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: P-00V-EEZ

DOI: 10.1016/j.bbamem.2021.183729

Abstract (EN): Fluorescence spectroscopy is used to characterize the partition of three second-generation D,L-alpha-cyclic peptides to two lipid model membranes. The peptides have proven antimicrobial activity, particularly against Gram positive bacteria, and the model membranes are formed of either with 1,2-dimyristoyl-sn-glycero-3-phospho- (1'- rac-glycerol) (DMPG) or its mixture with 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), at a molar ratio of (1:1). The peptide's intrinsic fluorescence was used in the Steady State and/or Time Resolved Fluorescence Spectroscopy experiments, showing that the peptides bind to the membranes, and the extent of their partition is thereof quantified. The peptide-induced membrane leakage was followed using an encapsulated fluorescent dye. Overall, the partition is mainly driven by electrostatics, but also involves hydrophobic interactions. The introduction of a hydrocarbon tail in one of the residues of the parent peptide, CPR, adjacent to the tryptophan (Trp) residue, significantly improves the partition of the modified peptides, CPRT10 and CPRT14, to both membrane systems. Further, we show that the length of the tail is the main distinguishing factor for the extension of the partition process. The parent peptide induces very limited leakage, at odds with the peptides with tail, that promote fast leakage, increasing in most cases with peptide concentration, and being almost complete for the highest peptide concentration and negatively charged membranes. Overall, the results help the unravelling of the antimicrobial action of these peptides and are well in line with their proven high antimicrobial activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11