Biomedical Applications of Peptidomimetics

Diagnostic Agents for Alzheimer’s Disease

Because Alzheimer’s disease can resemble other forms of dementia, it can be extremely difficult to diagnose. One of the hallmarks of Alzheimer’s is the clumping together, or aggregation, of a small protein fragment, or peptide, called beta-amyloid. If these peptide clumps could be detected early it would provide not only a firm diagnosis but also a window of opportunity for early intervention, care and long-term planning. Recently, scientists have modified beta-amyloid peptides so that they could be detected in mice with the use of magnetic resonance imaging (MRI). The Kirshenbaum lab, working with colleagues at the NYU Medical School, now plan to modify these peptides so they can eventually be optimized for use in humans.

The research will focus on several fundamental features that will make the imaging agents both efficient and safe. The stability within the body will be enhanced by incorporation of non-natural “peptoid” components. A library of peptide mimetic compounds will be evaluated to discover those that can easily penetrate into the brain. We will ensure that though the peptoids will bind tightly to the beta-amyloid, they will not exacerbate aggregation of the natural peptide. Ultimately, it may be possible to design compounds that will interfere with the aggregation process, and prevent the formation of amyloid deposits within the brain. Therefore, these peptide mimetics may serve not only in diagnosis of Alzheimer’s but also as potential therapeutics.

This research is supported by the Alzheimer's Association.

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