Rationally designed peptoids modulate aggregation of amyloid-beta 40 J. Phillip Turner, Tammy Lutz-Rechtin, Kelly A. Moore, Lauren Rogers, Omkar Bhave, Melissa A Moss, Shannon L Servoss, ACS Chem. Neurosci., Just Accepted Manuscript. Publication Date (Web): April 1, 2014
Alzheimer’s disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques comprised of aggregated amyloid-beta protein (Aβ) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent Aβ aggregation and thus the build-up of Aβ plaques; however a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of Aβ) was tested for its ability to modulate Aβ aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross beta sheet of Aβ. JPT1 was found to modulate Aβ40 aggregation, specifically decreasing lag time and the total number of aggregates formed. These results suggest that peptoids may be able to limit the formation of Aβ aggregates that are associated with AD.
Keyword: high temperature gate valves