IOCB Fellowships – next submission deadline on 1 October
17 September 2020
IOCB Prague is opening up to 10 postdoctoral positions in chemistry and biochemistry per year funded by the IOCB Fellowship program. The fellowship is granted for one year with…
How to measure binding affinity of IGF2 analogues
11 September 2020
In adult humans, the physiological function of insulin-like growth factor 2 (IGF2) has not yet been entirely explained, even though it is the most abundant insulin-family protein…
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Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors
European Journal of Medicinal Chemistry 208 : Early View (2020).
The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 ± 2 nM and its 8-C-glucoside orientin with an IC50 of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 Å resolution and quambalarine B at 2.5 Å resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.
From π Bonds without σ Bonds to the Longest Metal–Metal Bond Ever: A Survey on Actinide–Actinide Bonding in Fullerenes
Inorganic Chemistry 59 (17): 12608–12615 (2020).
Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and Clear Blood-Stage Malaria
Cell Chemical Biology 2020 : Early View (2020).
A radioligand binding assay for the insulin-like growth factor 2 receptor
PLOS ONE 15 (9): e0238393 (2020).