Search results for "Diazirine"
showing 3 items of 3 documents
Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells.
2012
Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimer´s disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Compounds named γ-secretase modulators (GSMs) can shift the substrate cleavage specificity of γ-secretase toward the production of non-amyloidogenic, shorter Aβ fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of …
Experimental and DFT Studies on Competitive Heterocyclic Rearrangements. Part 2:1 A One-Atom Side-Chain versus the Classic Three-Atom Side-Chain (Bou…
2007
The experimental investigation of the base-catalyzed rearrangements of 3-acylamino-1,2,4-oxadiazoles evidenced a new reaction pathway which competes with the well-known ring-degenerate Boulton-Katritzky rearrangement (BKR). The new reaction consists of a one-atom side-chain rearrangement that is base-activated, occurs at a higher temperature than the BKR, and irreversibly leads to the corresponding 2-acylamino-1,3,4-oxadiazoles. An extensive DFT study is reported to elucidate the proposed reaction mechanism and to compare the three possible inherent routes: (i) the reversible three-atom side-chain ring-degenerate BKR, (ii) the ring contraction-ring expansion route (RCRE), and (iii) the one-…
Synthesis, X-ray Structure Determination, and Comprehensive Photochemical Characterization of (Trifluoromethyl)diazirine-Containing TRPML1 Ligands
2021
Potential (trifluoromethyl)diazirine-based TRPML1 ion channel ligands were designed and synthesized, and their structures were determined by single-crystal X-ray diffraction analysis. Photoactivation studies via 19F NMR spectroscopy and HPLC-MS analysis revealed distinct kinetical characteristics in selected solvents and favorable photochemical properties in an aqueous buffer. These photoactivatable TRPML activators represent useful and valuable tools for TRPML photoaffinity labeling combined with mass spectrometry.