Effect of several compounds on the process of reduction of the 20-keto group of corticosteroids by a culture of Mycobacterium globiforme

The effect of certain metabolites produced in the metabolism of carbohydrates, proteins and fats on the reduction of the 20-keto group in a number of corticosteroids (prednisone, prenisolone, 6 alpha-methylprednisolone) was studied with the culture of Mycobacterium globiforme. The metabolites and inhibitors of the respiration chain were found to stimulate the 20 beta-reduction of a steroid molecule. The inhibitor of oxidative phosphorylation, 2,4-dinitrophenol, inhibited the reduction of the 20-keto group in a steroid.     

The influence of compound aITEL1296 on telomerase activity and growth of cancer cells

Telomerase is a ribonucleoprotein complex, which synthesizes telomeric repeats and which has been identified as a promising target for anticancer therapy. Here we have investigated the effect of a new compound aITEL1296 on telomerase activity. aITEL1296 effectively inhibited telomerase activity; its inhibitory activity was a bit higher (IC₅₀ = 0.19 ± 0.02 ng/mL) than that of BIBR1532, one of the most potent telomerase inhibitors known to date. In addition to telomerase inhibition aITEL1296 activated apoptotic mechanisms and effectively suppressed proliferation of tumor cell lines (GI₅₀ = 5.0 ± 0.2 ng/mL for most sensitive cell line LnCap) but not normal fibroblast cell line.     

A weakened interface in the P182L variant of HSP27 associated with severe Charcot‐Marie‐Tooth neuropathy causes aberrant binding to interacting proteins

HSP27 is a human molecular chaperone that forms large, dynamic oligomers and functions in many aspects of cellular homeostasis. Mutations in HSP27 cause Charcot‐Marie‐Tooth (CMT) disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of CMT disease is triggered by the P182L mutation in the highly conserved IxI/V motif of the disordered C‐terminal region, which interacts weakly with the structured core domain of HSP27. Here, we observed that the P182L mutation disrupts the chaperone activity and significantly increases the size of HSP27 oligomers formed in vivo, including in motor neurons differentiated from CMT patient‐derived stem cells. Using NMR spectroscopy, we determined that the P182L mutation decreases the affinity of the HSP27 IxI/V motif for its own core domain, leaving this binding site more accessible for other IxI/V‐containing proteins. We identified multiple IxI/V‐bearing proteins that bind with higher affinity to the P182L variant due to the increased availability of the IxI/V‐binding site. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27 and suggest that the IxI/V motif plays an important, regulatory role in modulating protein–protein interactions.