Poster Presentation 12th Australian Peptide Conference 2017

β‑peptide self-assembly as a new strategy for in situ bacterial detection and inhibition (#162)

Ketav Kulkarni 1 , Jennifer Payne 1 , Thierry Izoré 1 , Mark P Del Borgo 1 , Max J Cryle 1 , Mibel Aguilar 1
  1. Monash University, Monash, VICTORIA, Australia

We have shown the ability of helical β3-peptides to self-assemble and form hierarchical structures,1 such as fibres, which have been used to create new materials.2 The unique modularity of the self-assembling process allows us to further decorate the β3‑peptides with functional payloads.3 We have also developed different strategies to overcome the paucity of orthogonal protecting groups for the effective derivatisation of β3-peptide monomers on solid support, thereby attaching a variety of cell recognition motifs to transform them into biomaterials.4 To showcase the versatility and robustness of the β3-peptide self‑assembly, we have recently conjugated Vancomycin, a sterically demanding glycopeptide antibiotic, onto a tri-β3-peptide via click chemistry and imaged the assembly and co-assembly, with a lipidated tri-β3-peptide, using high resolution atomic force microscopy. The peptide assemblies at different ratios and concentrations were further investigated for their ability to inhibit the growth of S. aureus (MRSA and VISA strain). The association of fibrous assemblies with S. aureus were imaged using electron microscopy confirming the in situ aggregation and self-assembly of the Vancomycin-β3‑peptide surrounding the bacterial cell surface. A fluorescently labelled Vancomycin-β3‑peptide conjugate was also synthesised and imaged using fluorescence microscopy, thus demonstrating β3‑peptide supramolecular assemblies as a new strategy for in situ bacterial detection and inhibition.

 

1 Del Borgo, M.P. et al. Angew. Chem. Int. Ed. 2013, 52, 8266-8270. Supramolecular SelfAssembly of NAcetylCapped βPeptides Leads to Nanoto Macroscale Fiber Formation

2 Motamed, S. et al. Soft Matter 2016, 12, 2243-2246 A self-assembling β-peptide hydrogel for neural tissue engineering

3 Luder K. et al. Chem. Commun. 2016, 52, 4549-4552 Decorated self-assembling β3-tripeptide foldamers form cell adhesive scaffolds

4 Kulkarni, K. et al. Chem. Commun. 2016, 52, 5844-5847 Orthogonal strategy for the synthesis of dual-functionalised β3‑peptide based hydrogels