Amyloid aggregation involves a complicated nucleation-dependent polymerization and many devastating human neurodegenerative diseases. While many strategies applied to prevent amyloid aggregation appear promising for potential therapeutics, it remains largely uncertain by which mechanism inhibition exactly occurs. To gain more mechanistic insights, we introduce multivalent polymer conjugates (mPCs) that may preferentially target and stabilize amyloid oligomers, and thus inhibit amyloid aggregation. To demonstrate this approach, we first conjugate polymers with multiple small-molecule or peptide-based inhibitors to target amyloid � (A�) aggregation associated with Alzheimer's disease. Our studies show that mPCs can far more effectively inhibit A� aggregation than their monomeric counterparts. The inhibition of A� aggregation by mPCs may occur through stabilizing A� oligomers, which may also reduce toxicity from A� aggregation. We envision that the concept of mPCs can be generalized in different amyloid aggregation studies and provide a new avenue to develop polymer conjugate therapeutics for amyloid-related diseases and others. 

Multivalent polymer conjugates targeting amyloid oligomers

246th National Meeting (2013)

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