Graduation Year
2025
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Chemistry
Reader 1
Professor Daniel J. O'Leary
Reader 2
Professor Thomas Vasquez
Terms of Use & License Information
Abstract
As the seventh leading cause of death in the U.S., Alzheimer’s disease (AD) poses a challenge to the health of individuals and public services that support them. The U.S. Food and Drug Administration (FDA) approves 5 medications that manage the symptoms of AD, though no treatment for AD exists. Research demonstrates the therapeutic potential of the secreted amyloid precursor protein alpha (sAPP⍺) as resistant to AD neurodegeneration. However, its relatively large size of 30 kDa prevents permeation of the blood-brain-barrier (BBB) necessary for effectively treating AD. The Rose Lab from the Open University in the UK has identified the arginine-glutamine-arginine (RER) tripeptide sequence as the smallest, active domain of sAPP⍺ capable of crossing the BBB and resists amnesia. While they claim that both fluorescein- and biotin-labelled RER crosses the BBB, private communication with the party responsible for their syntheses revealed a conjugated linker not disclosed in their papers. They also proposed the collapsin response mediator protein 2 (CRMP2) as the binding partner for RER, but lacked characterization of its binding. In collaboration with Parfitt Lab in the Neuroscience Department at Pomona College, this study aims to determine whether these peptides permeate the BBB, identify their molecular targets, and characterize their binding. Following the solid phase peptide synthesis (SPPS), desired N-terminal modifications, then in vivo administration of these peptides, novel approaches featuring “click” chemistry will be used to evaluate the permeation of the BBB and identify molecular targets of these tripeptides. Such results would support the therapeutic efficacy of sAPP⍺-derived peptides and advance AD treatment as a whole.
Recommended Citation
Abalos, Zheous and O'Leary, Daniel J. PhD, "A Click Chemistry-Based Approach to Assessing sAPP⍺ Derived-Peptides as an Alzheimer’s Therapeutic: Evaluation of Blood Brain Barrier Permeability and Identification of its Molecular Targets" (2025). Pomona Senior Theses. 357.
https://scholarship.claremont.edu/pomona_theses/357
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
