Evaluating synthetic fragments of α-synuclein for influence on α-synuclein aggregation behavior

CHED 570

Margaret Blattner, Cynthia Crosswhite, Katharine Walsham, and Julia H Miwa, jmiwa@wellesley.edu. Department of Chemistry, Wellesley College, Wellesley, MA 02481
Parkinson's disease (PD) is characterized by the depletion of dopamine linked to the presence of Lewy bodies in the substantia nigra. These fibrillar cytoplasmic inclusions are composed primarily of α-synuclein. The function of natively unfolded α-synuclein is currently unknown, but α-synuclein aggregation has been linked to the etiology of PD. The project goals are to identify key fragments of α-synuclein and key lysine residues that influence aggregation behavior. The project strategy includes: synthesizing fragments of α-synuclein and testing for inhibition of protein aggregation, replacing lysine residues with alanine residues in active fragments, and incorporating lysine residues modified with a small molecule into active fragments. In phase one, peptides with 20 amino acid residues were synthesized using solid-phase peptide synthesis. As the aggregation behavior in the presence and absence of the fragments is compared, we hope to increase the understanding of α-synuclein aggregation behavior in the progression of PD.