Event Title

Synthesis and Evaluation of Symmetrical Biphenyltetrols as Aggregation Inhibitors for Alzheimer’s Amyloid-beta Peptide

Poster Number

47

Presenter Information

Sarah Wicks, Winthrop University

Faculty Mentor

Robin K. Lammi, Ph.D. and James M. Hanna, Jr., Ph.D.

College

College of Arts and Sciences

Department

Chemistry, Physics and Geology

Location

Richardson Ballroom

Start Date

24-4-2015 1:20 PM

End Date

24-4-2015 2:50 PM

Description

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.

Comments

Sarah Wicks is a McNair Scholar.

Presented at the South Carolina TRiO McNair Symposium, June 2014; the SAEOPP McNair/SSS Scholars Research Conference, June 2014; the Southeastern Regional Meeting of the American Chemical Society, October 2014; the South Carolina INBRE Spring Symposium, February 2015; and the 249th National Meeting of the American Chemical Society, March 2015

Supported by an NIH-INBRE grant from the National Center for Research Resources and the National Institute of General Medical Sciences

Winner, 2nd Place, Life Sciences Oral Presentations, SAEOPP Conference, June 2014

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Apr 24th, 1:20 PM Apr 24th, 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.