Design and synthesis of a C2-symmetric cyclic decapeptide and its peptidomimetic as potential inhibitors against amyloid-beta aggregation

A C2-symmetric cyclic decapeptide and its peptidomimetic based on the KLVFF fragment of amyloid-beta (Abeta) were designed and synthesized as potential inhibitors against Abeta aggregation in Alzheimer's disease. These compounds were efficiently synthesized using solution- and solid-phase peptide synthesis. Thioflavin-T assays revealed that both the cyclic decapeptide and its chloroalkene dipeptide isostere (CADI)-containing peptidomimetic significantly inhibited Abeta aggregation. These results demonstrated the potential of C2-symmetric cyclic peptides and peptidomimetics as effective Abeta aggregation inhibitors for Alzheimer's disease therapies.