An inorganic pyrophosphatase (PPases) was cloned from the hyperthermophilic archaeon Pyrococcus horikoshii and was expressed in and purified from Escherichia coli. The recombinant inorganic pyrophosphatase (PhPPase) exhibited robust catalytic activity of the hydrolysis of pyrophosphate into two orthophosphates at high temperatures (70 degrees C to 95 degrees C). Thermostable pyrophosphatase activity was applied into polymerase chain reaction (PCR) due to its ability to push chemical equilibrium toward the synthesis of DNA by removing pyrophosphate from the reaction. A colorimetric method using molybdate and reducing agents was used to measure PCR progress by detecting and quantifying inorganic phosphate in the PhPPase-coupled PCR mixture. Compared to PCR mixtures without PhPPase, the thermostable PhPPase enhanced the amount of PCR product in the same number of cycles. Thus, thermostable PPase may overcome the limitations of thermodynamically unfavorable DNA polymerization in PCR by yielding more products.
PRMT6 catalyzes monomethylation and asymmetric dimethylation of arginine residues in various proteins, plays important roles in biological processes and is associated with multiple cancers. While there are several reported PRMT6 inhibitors, a highly selective PRMT6 inhibitor has not been reported to date. Furthermore, allosteric inhibitors of protein methyltransferases are rare. Here we report the discovery and characterization of a first-in-class, highly selective allosteric inhibitor of PRMT6, SGC6870. SGC6870 is a potent PRMT6 inhibitor (IC50 = 77 ± 6 nM) with outstanding selectivity for PRMT6 over a broad panel of other methyltransferases and non-epigenetic targets. Notably, the crystal structure of the PRMT6–SGC6870 complex and kinetic studies revealed SGC6870 binds a unique, induced allosteric pocket. Additionally, SGC6870 engages PRMT6 and potently inhibits its methyltransferase activity in cells. Moreover, SGC6870’s enantiomer, SGC6870N, is inactive against PRMT6 and can be utilized as a negative control. Collectively, SGC6870 is a well-characterized PRMT6 chemical probe and valuable tool for further investigating PRMT6 functions in health and disease.
5-Hydroxychromone, an Alternative Scaffold for anti-HCV 1,3-Diketo Acid (DKA). -Novel chromone derivatives of type (I) are prepared. Most compounds show moderate antiviral activity; substances with electron-withdrawing substituents are more potent than those with electron-donating groups. -(LEE, C.; PARK, K.-S.; PARK HYE RI; PPARK JUN CHEOL; LEE, B.; KIM, D.-E.; CHONG*, Y.; Bull.
Alcohols Q 0230Octanol-Accelerated Baylis-Hillman Reaction. -The use of 2 equiv. of octanol as solvent accelerates the reaction remarkably compared to the use of MeOH. Aromatic aldehydes bearing electron-withdrawing substituents and unactivated aliphatic aldehydes are readily converted into the desired products in good to quantitative yields. The formation of the vinyl dimer (VIII) is completely suppressed in most cases. For electron-rich aldehydes, even the use of octanol is not optimal. -(PARK, K.-S.; KIM, J.; CHOO, H.; CHONG*, Y.; Synlett 2007, 3, 395-398; Dep.
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