Post-translational modification (PTM) on protein plays important roles in the regulation of cellular function and disease pathogenesis. The systematic analysis of PTM dynamics presents great opportunities to enlarge the target space by PTM allosteric regulation. Here, we presented a framework by integrating the sequence, structural topology, and particular dynamics features to characterize the functional context and druggabilities of PTMs in the well-known kinase family. The machine learning models with these biophysical features could successfully predict PTMs. On the other hand, PTMs were identified to be significantly enriched in the reported allosteric pockets and the allosteric potential of PTM pockets were thus proposed through these biophysical features. In the end, the covalent inhibitor DC-Srci-6668 targeting the PTM pocket in c-Src kinase was identified, which inhibited the phosphorylation and locked c-Src in the inactive state. Our findings represent a crucial step toward PTM-inspired drug design in the kinase family.
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Tanshinones is an important type of natural products isolated from Salvia miltiorrhiza Bunge with various bioactivities.
Tanshinone IIa, cryptotanshinone and tanshinone I are three kinds of tanshinones which have been widely investigated. Particularly, sodium
tanshinone IIa sulfonate is a water-soluble derivative of tanshinone IIa and it is used in clinical in China for treating cardiovascular diseases.
In recent years, there are increasing interests for investigation of tanshinones derivatives in various diseases. This article present a review of
the anti-atherosclerotic effects, cardioprotective effects, anticancer activities, antibacterial activities and antiviral activities of tanshinones and
structural modification work in recent years.
A photo-induced imidation process of carboxylic acids is described. Numerous carboxylic acids could convert to β-sulfonyl imides in the presence of N-sulfonyl ynamides under the visible light irradiation. Control experiments...
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