Impact of amphiphilic peptide dendrimers on proteins self-assembly

Introduction. Improper peptide/protein folding followed by fibrillation is regarded a main reason of neurodegenerative diseases. For this reason major efforts have been achieved to find molecules that can inhibit or interfere... [ view full abstract ]

Introduction. Improper peptide/protein folding followed by fibrillation is regarded a main reason of neurodegenerative diseases. For this reason major efforts have been achieved to find molecules that can inhibit or interfere with aggregation process. 

Methods. We will present studies on interactions of low molecular weight amphiphilic peptide dendrimers with pH- and temperature-dependent secondary structures generated by model polypeptide systems: cationic polylysine (PLL) and anionic polyglutamic acid (PLGA). Interactions of dendrimers with self-assembled peptides were investigated in detail by application of circular dichroism (CD), UV and fluorescence spectroscopy. To follow conformational transitions (self-assembly – disassembly processes) three dyes: Congo Red, curcumin and Thioflavin T were applied independently. Parallel microscopic studies showed macroscopic manifestation of the formed secondary structures and mechanism of their propagation.

Results. It was found that an optimized balance between hydrophilicity and lipophilicity as well as concentration of the designed dendrimeric molecules is the critical condition for their assembling (or not) with model proteins. Moreover, careful controlling of the commercial mixtures of polypeptides used in aggregation studies seems to be another important point that will be addressed.

This work was supported by grant from the National Science Centre, UMO-2015/19/B/ST503547.