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

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.