The Real-Time Validation of the Effectiveness of Third-Generation Hyperbranched Poly(epsilon-lysine) Dendrons-Modified KLVFF Sequences to Bind Amyloid-beta(1-42) Peptides Using an Optical Waveguide Light-Mode Spectroscopy System

The aggregation of cytotoxic amyloid peptides (A beta(1-42)) is widely recognised as the cause of brain tissue degeneration in Alzheimer's disease (AD). Indeed, evidence indicates that the deposition of cytotoxic A beta(1-42) plaques formed through the gradual aggregation of A beta(1-42) monomers into fibrils determines the onset of AD. Thus, distinct A beta(1-42) inhibitors have been developed, and only recently, the use of short linear peptides has shown promising results by either preventing or reversing the process of A beta(1-42) aggregation. Among them, the KLVFF peptide sequence, which interacts with the hydrophobic region of A beta(16-20), has received widespread attention due to its ability to inhibit fibril formation of full-length A beta(1-42). In this study, hyperbranched poly-L-lysine dendrons presenting sixteen KLVFF at their uppermost molecular branches were designed with the aim of providing the KLVFF sequence with a molecular scaffold able to increase its stability and of improving A beta(1-42) fibril formation inhibitory effect. These high-purity branched KLVFF were used to functionalise the surface of the metal oxide chip of the optical waveguide lightmode spectroscopy sensor showing the more specific, accurate and rapid measurement of A beta(1-42) than that detected by linear KLVFF peptides.