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Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway

J. Alzheimers Dis.. 2017-01; 
FisherCarolyn L, ResnickRoss J, DeSoumya, AcevedoLucila A, LuKun Ping, SchroederFrank C, NicholsonLin
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… Antibodies. Rabbit anti-sAβPPβ (poly8134, 813401) and the mouse monoclonal antibody 6E10 (803001) were purchased from BioLegend (San Diego, CA) and the anti-β-tubulin mouse monoclonal antibody (2G7D4, A01717-40) was acquired from GenScript (Piscataway, NJ) …

摘要

The cis/trans isomerization of X-Pro peptide bonds in proteins in some instances acts as a molecular switch in biological pathways. Our prior work suggests that the cis isomer of the phospho-Thr668-Pro669 motif, located in the cytoplasmic domain of the amyloid-β protein precursor (AβPP), is correlated with an increase in amyloidogenic processing of AβPP and production of amyloid-beta (Aβ), the neurotoxic peptide fragment in Alzheimer's disease (AD). We designed a 100% cis-locked cyclic dipeptide composed of cyclized phospho-Thr-Pro (pCDP) as a mimic for this putative pathological conformation, and three phosphate-blocked derivatives (pCDP-diBzl, pCDP-Bzl, and pCDP-diPOM). Two H4 neuroglioma cell... More

关键词

Alzheimer’s disease,amyloid beta-protein precursor,cyclic dipeptides,diketopiperazine,phosphorylated Th