Journal: ACS Central Science

Article Title: Mapping the Azolog Space Enables the Optical Control of New Biological Targets

doi: 10.1021/acscentsci.8b00881

Figure Lengend Snippet: Photophysical evaluation and LTA 4 -hydrolase peptidase assay with LTA 4 H-Photoswitch . (A, B) Enzymatic reactions catalyzed by LTA 4 -hydrolase. (C) The UV–vis spectrum of LTA 4 H-Photoswitch in the dark-adapted (black, trans ), 365 nm adapted (gray, cis ), and 460 nm adapted (blue, trans ) photostationary states. (D) Reversible cycling between isomers with alternating illumination at 365/460 nm. (E) Schematic depiction of l -alanine 4-nitroanilide cleavage by LTA 4 H (PDB: 2VJ8). (F) LTA 4 H peptidase assay with LTA 4 h (1.1 μg) and l -alanine 4-nitroanilide (1 mM) in the presence and absence of cis -LTA 4 H-Photoswitch at different concentrations. Samples were irradiated with 460 nm light after 4 min to yield trans -LTA 4 H-Photoswitch . The slope of 4-nitroaniline absorption (λ = 410 nm) was plotted. (G, H) Representative traces of 4-nitroaniline absorption (λ = 410 nm) before and after application of 460 nm light. Samples were run in triplicates. Error bars represent SEM ** p < 0.01, n.s., not significant, student’s t -test.

Article Snippet: In good agreement with the computational prediction, trans- LTA 4 H-Photoswitch was a more potent inhibitor of LTA 4 H peptidase than the cis -isomer ( Figure ).

Techniques: Irradiation

Journal: ACS Central Science

Article Title: Mapping the Azolog Space Enables the Optical Control of New Biological Targets

doi: 10.1021/acscentsci.8b00881

Figure Lengend Snippet: Synthesis and isomerization of LTA 4 h-Photoswitch . (A) 3D-overlays of parent azologable compounds (gray) with corresponding cis - and trans- azologs (yellow) and 3DAPfp scores of 3D shape similarity comparison. (B) Design of LTA 4 h-Photoswitch based on the azologization of a benzyl phenyl ethers. (C) Chemical synthesis of LTA 4 h-Photoswitch .

Article Snippet: In good agreement with the computational prediction, trans- LTA 4 H-Photoswitch was a more potent inhibitor of LTA 4 H peptidase than the cis -isomer ( Figure ).

Techniques: Comparison