Speaker: Lyric Gordon, MSCB student
Title: Developing Peptide Based Inhibitors Targeting Amyloid Beta for Alzheimer’s Disease
Abstract: Alzheimer’s disease (AD) is defined as a progressive neurological disorder that has adverse effects on one’s cognitive function over time. Currently identified as the prevalent antecedent of dementia, this disease is ranked seventh in the leading causes of death by the CDC. Since its discovery in 1906, there’s been a 145% increase in deaths observed by researchers. Unfortunately, scientists have been unsuccessful in both curing and eradicating the diseases’ harsh symptoms. Amyloid-Beta (Ab) is a protein which accumulates into neurofibrillary tangles and extracellular plaques when sliced by b- and g- secretases. It is placed at the forefront as the cause of AD. The aim of this project is to develop and improve peptide-based inhibitors by modifying previously tested peptide sequences that were successful in targeting and inhibiting Aβ. In this research, various peptides are designed, synthesized and investigated to analyze their binding affinity to Ab via liquid chromatography- mass spectrometry (LC-MS) based selected ion monitoring (SIM) assays. Dissociation constant (Kd) is used to measure the binding affinity between amyloid-beta and peptide inhibitors. Various linear and cyclic peptide were synthesized, characterized, and analyzed.  Linear peptide, LP-1 presented the strongest binding affinity of all peptides with a Kd value of 1.73 nM, followed by LP-3 with a K_d value at 19.69 nM. Cyclic peptide displayed a weaker binding in comparison to its linear counterpart at 49.12 nM. Molecular docking was used to predict and support the exhibited binding strength and interactions of synthesized peptides with Ab. In future, these potent peptides will be tested for Ab inhibition using the cell-based assay and animal model, thus providing new avenues to aid in the fight against AD.