Title of Abstract
Synthesis and Evaluation of Symmetrical Biphenyltetrols as Aggregation Inhibitors for Alzheimer’s Amyloid-beta Peptide
Poster Number
47
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
Robin K. Lammi, Ph.D. and James M. Hanna, Jr., Ph.D.
Abstract
Inhibition of amyloid-beta peptide (Abeta) aggregation is one therapeutic target for prevention and treatment of Alzheimer’s disease. We have previously demonstrated that biphenyl-3,3′,4,4′-tetrol (3,4-BPT) effectively abrogates Abeta aggregation at stoichiometric concentrations. To investigate this molecular architecture and determine how the positioning of the hydroxyl hydrogen-bond donors impacts inhibitor efficacy, we have synthesized five additional symmetrical biphenyltetrols (2,3-, 2,4- 2,5- 2,6- and 3,5-BPT). Congo red and Thioflavin T dye-binding assays were employed to monitor Abeta aggregation as a function of time and determine inhibitor IC50 values for reducing equilibrium levels of aggregation. The six characterized isomers exhibit a range of IC50 values spanning more than one order of magnitude. Circular dichroism and transmission electron microscopy measurements, in progress, will enable comparison of secondary structural transitions and aggregate morphologies in the presence and absence of inhibitors. Collectively, these results will aid in the design of unsymmetrical biphenyltetrols and related inhibitor architectures.
Start Date
24-4-2015 1:20 PM
End Date
24-4-2015 2:50 PM
Synthesis and Evaluation of Symmetrical Biphenyltetrols as Aggregation Inhibitors for Alzheimer’s Amyloid-beta Peptide
Richardson Ballroom
Inhibition of amyloid-beta peptide (Abeta) aggregation is one therapeutic target for prevention and treatment of Alzheimer’s disease. We have previously demonstrated that biphenyl-3,3′,4,4′-tetrol (3,4-BPT) effectively abrogates Abeta aggregation at stoichiometric concentrations. To investigate this molecular architecture and determine how the positioning of the hydroxyl hydrogen-bond donors impacts inhibitor efficacy, we have synthesized five additional symmetrical biphenyltetrols (2,3-, 2,4- 2,5- 2,6- and 3,5-BPT). Congo red and Thioflavin T dye-binding assays were employed to monitor Abeta aggregation as a function of time and determine inhibitor IC50 values for reducing equilibrium levels of aggregation. The six characterized isomers exhibit a range of IC50 values spanning more than one order of magnitude. Circular dichroism and transmission electron microscopy measurements, in progress, will enable comparison of secondary structural transitions and aggregate morphologies in the presence and absence of inhibitors. Collectively, these results will aid in the design of unsymmetrical biphenyltetrols and related inhibitor architectures.
