Jump to main content
Jump to site search

Issue 45, 2016
Previous Article Next Article

The singular behavior of a β-type semi-synthetic two branched polypeptide: three-dimensional structure and mode of action

Author affiliations

Abstract

Dendrimeric peptides make a versatile group of bioactive peptidomimetics and a potential new class of antimicrobial agents to tackle the pressing threat of multi-drug resistant pathogens. These are branched supramolecular assemblies where multiple copies of the bioactive unit are linked to a central core. Beyond their antimicrobial activity, dendrimeric peptides could also be designed to functionalize the surface of nanoparticles or materials for other medical uses. Despite these properties, however, little is known about the structure–function relationship of such compounds, which is key to unveil the fundamental physico-chemical parameters and design analogues with desired attributes. To close this gap, we focused on a semi-synthetic, two-branched peptide, SB056, endowed with remarkable activity against both Gram-positive and Gram-negative bacteria and limited cytotoxicity. SB056 can be considered the smallest prototypical dendrimeric peptide, with the core restricted to a single lysine residue and only two copies of the same highly cationic 10-mer polypeptide; an octanamide tail is present at the C-terminus. Combining NMR and Molecular Dynamics simulations, we have determined the 3D structure of two analogues. Fluorescence spectroscopy was applied to investigate the water-bilayer partition in the presence of vesicles of variable charge. Vesicle leakage assays were also performed and the experimental data were analyzed by applying an iterative Monte Carlo scheme to estimate the minimum number of bound peptides needed to achieve the release. We unveiled a singular beta hairpin-type structure determined by the peptide chains only, with the octanamide tail available for further functionalization to add new potential properties without affecting the structure.

Graphical abstract: The singular behavior of a β-type semi-synthetic two branched polypeptide: three-dimensional structure and mode of action

Back to tab navigation

Supplementary files

Publication details

The article was received on 06 Aug 2016, accepted on 18 Oct 2016 and first published on 18 Oct 2016


Article type: Paper
DOI: 10.1039/C6CP05464A
Citation: Phys. Chem. Chem. Phys., 2016,18, 30998-31011
  •   Request permissions

    The singular behavior of a β-type semi-synthetic two branched polypeptide: three-dimensional structure and mode of action

    G. Manzo, I. Serra, A. Pira, M. Pintus, M. Ceccarelli, M. Casu, A. C. Rinaldi and M. A. Scorciapino, Phys. Chem. Chem. Phys., 2016, 18, 30998
    DOI: 10.1039/C6CP05464A

Search articles by author

Spotlight

Advertisements