Proline-rich, polybasic peptides are a structurally distinct class of amyloid-reactive peptides

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Systemic amyloidosis involves misfolded protein buildup, causing organ dysfunction.
• Current treatments prevent amyloid accumulation but don't clear existing deposits.
• A need exists for therapeutics that promote amyloid clearance by phagocytic cells.

Purpose of the Study:

• To develop novel polybasic peptides targeting amyloid deposits.
• To investigate the binding specificity and potency of these PxR peptides against amyloid.

Main Methods:

• Probed amyloid-reactivity and specificity using human and mouse tissue sections.
• Quantified amyloid binding to synthetic fibrils and patient-derived extracts via immunosorbent assays.
• Assessed PxR peptide stability in mouse and human serum using bioactivity assays.

Main Results:

• PxR peptides exhibit high specificity and potency for amyloid and associated heparan sulfate.
• These peptides are predicted to form a positively charged linear face for amyloid binding.
• PxR peptides demonstrated resistance to serum proteases, indicating stability.

Conclusions:

• Polybasic PxR peptides act as pan-amyloid binding agents.
• These peptides can facilitate the targeted delivery of amyloid-clearing therapeutics.
• PxR peptides represent a promising new therapeutic strategy for systemic amyloidosis.