Exploring Aspartic Protease Inhibitor Binding to Design Selective Antimalarials.

Selectivity is a major issue in the development of drugs targeting pathogen aspartic proteases. Here, we explore the selectivity-determining factors by studying specifically designed malaria aspartic protease (plasmepsin) open-flap inhibitors. Metadynamics simulations are used to uncover the complex binding/unbinding pathways of these inhibitors and describe the critical transition states in atomistic resolution.

The influence of an external magnetic field on the dynamics of magnetite reduction with hydrogen.

The kinetics of hydrogen reduction of magnetite was investigated in different magnetic fields. The magnetic moment measurements were used for the control of the reaction. A strong difference in the magnetic properties of the reaction results was obtained for applied strong and weak magnetic fields.

Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. Because of its heterogeneity and lack of hormone receptors or HER2 expression, targeted therapy is limited. Here, by performing a functional siRNA screening for 2-OG-dependent enzymes, we identified gamma-butyrobetaine hydroxylase 1 () as an essential gene for TNBC tumorigenesis.

Synthesis and quantitative structure-activity relationship of hydrazones of N-amino-N'-hydroxyguanidine as electron acceptors for xanthine oxidase.

A series of new N-hydroxyguanidines were synthesized and tested for electron acceptor activity on bovine milk xanthine oxidase using xanthine as reducing substrate. Manual inspection of the structure-activity data revealed that molecules containing nitro groups ("set A") show a different structure-activity relationship pattern compared to non-nitro compounds ("set B"). Accordingly separate QSAR models were built and validated for the two sets.