Design of Zwitterionic Conjugated Polymers as Protein Aggregation Inhibitors.

Area of Science:

• Biomaterials Science
• Neuroscience
• Polymer Chemistry

Background:

• Protein misfolding and aggregation are central to neurodegenerative diseases such as Alzheimer's disease.
• Existing therapeutic strategies include small molecules, peptides, and polymers, but conjugated zwitterionic polymers remain unexplored for this application.

Purpose of the Study:

• To synthesize and evaluate novel conjugated polymers with zwitterionic sulfobetaine moieties and poly(ethylene glycol) chains as inhibitors of protein aggregation.
• To investigate the efficacy of these polymers in preventing and disrupting amyloid beta peptide (Aβ42) aggregation and fibril formation.

Main Methods:

• Synthesis of conjugated polymers functionalized with zwitterionic sulfobetaine and poly(ethylene glycol) side chains.
• In vitro assays to assess the inhibition of amyloid beta peptide (Aβ42) aggregation.
• Electron microscopy and other techniques to visualize and characterize amyloid fibril disruption and solubilization.

Main Results:

• The synthesized polymers demonstrated potent inhibition of amyloid beta peptide (Aβ42) aggregation.
• These polymers effectively disrupted and solubilized pre-formed amyloid fibrils.
• Dual functionality was observed, with significant fibril disaggregation at lower concentrations compared to existing alternatives, showing broad-spectrum protein protection.

Conclusions:

• Conjugated zwitterionic polymers represent a novel and highly effective class of protein aggregation inhibitors.
• These materials offer a promising therapeutic strategy for neurodegenerative diseases by targeting toxic protein aggregates.
• The developed polymers advance the field of biomedical materials for disease treatment.