The effect of terminal groups and halogenation of KLVFF peptide on its activity as an inhibitor of beta-amyloid aggregation

Abstract

The aggregation of A beta peptide into amyloid fibrils in the brain is associated with Alzheimer's disease (AD). Inhibition of A beta aggregation seemed a potential treatment for AD. It was previously shown that a short fragment of A beta peptide (KLVFF, 16-20) bound A beta inhibited its aggregation. In this work, using KLVFF peptide, we synthesized two peptide families and then evaluated their inhibitory capacities by conventional assays such as thioflavin T (ThT) fluorescence spectroscopy, turbidity measurement, and the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). The effect of peptide terminal groups on its inhibitory activity was first studied. Subsequently, the influence of halogenated amino acids on peptide anti-aggregation properties was investigated. We found that iodinated peptide with amine in the N and amide in the C termini, respectively, was the best inhibitor of A beta fibers formation. Halogenated peptides seemed to decrease the number of A beta fibrils; however, they did not reduce A beta cytotoxicity. The data obtained in this work seemed promising in developing potential peptide drugs for treatment of AD.