Alzheimer’s disease (AD) is a debilitating neurodegenerative disease for which there is no cure. Although AD involves multiple pathologies (e.g., metal dysregulation, inflammation, β-amyloid plaque aggregation), many drugs target only one cause of the disease. Moreover, challenges in the design of drugs which can penetrate the blood-brain barrier (BBB) have hindered the development of treatments for CNS diseases such as AD. Certain hydrophobic poly-N-substituted glycines, or peptoids, have high membrane penetrability and could be used to deliver drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), to the brain. We present the design, synthesis, and purification of a series of peptoids containing metal chelating groups to treat metal dysregulation. Ultimately, these molecules will be linked to NSAIDs to generate multifunctional AD drugs with anti-inflammatory and metal-chelating properties.

Design and synthesis of metal-chelating peptoids for the treatment of Alzheimer’s disease

251st National Meeting (2016)

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