Designing polymer–peptide conjugates to target dipeptide repeat aggregates implicated in amyotrophic lateral sclerosis

Abstract

Toxic dipeptide repeats such as the aggregating glycine–alanine (GA)_n peptide are implicated in the progression of amyotrophic lateral sclerosis (ALS), a lethal neuromuscular disease with an urgent need for new therapeutics. Here, we report polymer–peptide conjugates that prevent aggregation of (GA)₁₀. Optical density measurements and transmission electron microscopy demonstrate that conjugates prevent aggregation when co-incubated with (GA)₁₀ and disperse pre-aggregated (GA)₁₀. These results represent an important step toward a new generation of therapeutics for ALS and contribute to a growing body of literature demonstrating the potential of polymer–peptide conjugates as therapeutics.