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

The aggregation of cytotoxic amyloid peptides (Aβ(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 Aβ(1-42) plaques formed through the gradual aggregation of Aβ(1-42) monomers into fibrils determines the onset of AD. Thus, distinct Aβ(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 Aβ(1-42) aggregation. Among them, the KLVFF peptide sequence, which interacts with the hydrophobic region of Aβ(16-20), has received widespread attention due to its ability to inhibit fibril formation of full-length Aβ(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 Aβ(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 Aβ(1-42) than that detected by linear KLVFF peptides.