Preparation of Affinity Based Probes to Elucidate the Mode of Action of y-Secretase Modulators
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Syntes av affinitetsbaserade ligander för att undersöka funktionen hos y-sekretasmodulatorer (Swedish)
γ-Secretase is an enzyme that takes part of the breakdown of amyloid precursor protein (APP) into amyloid-β (Aβ) peptides. Aβ-peptides from this process can be linked to Alzheimer’s disease. γ-Secretase modulators (GSMs) have been reported in the literature to reduce the potentially dangerous variant of Aβ-peptides. However, the mechanism of the binding site for these modulators is poorly understood. In this report substances of affinity based probes (AfBPs) have been prepared that can be used as a method to extract the binding site. The AfBPs were constituted of a cross-linking group, a biotinyl group and a γ-secretase modulator. Different variants of the biotin probe were prepared to investigate if the activity of the original modulator could be retained. The report will show that this could be done.
In the future, the synthesised affinity based probes could be used to understand the mode of action of γ-secretase modulators. For instance the modulator could be incubated with the enzyme and the crosslinking group, when activated, covalently bind to a residue near the binding site. The complex could then be captured on avidin and the binding site be determined.
Place, publisher, year, edition, pages
2011. , 30 p.
Alzheimer’s disease (AD), γ-Secretase modulator (GSM), affinity based probe (AfBP), biotinyl, amyloid precursor protein (APP)
IdentifiersURN: urn:nbn:se:kth:diva-51162OAI: oai:DiVA.org:kth-51162DiVA: diva2:463572
Subject / course
Master of Science in Engineering - Chemical Science and Engineering
UppsokPhysics, Chemistry, Mathematics
Rotticci, DidierWaldman, Magnus
Somfai, Peter, Professor