7329-79-5Relevant articles and documents
Purine nucleoside phosphorylase-catalyzed, phosphate-independent hydrolysis of 2-amino-6-mercapto-7-methylpurine ribonucleoside
Cheng, Jianming,Farutin, Victor,Wu, Zhijun,Jacob-Mosier, Gayatry,Riley, Brad,Hakimi, Ryan,Cordes, Eugene H.
, p. 307 - 325 (1999)
In the presence of 1 mM phosphate, 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG) is a well-behaved substrate for calf spleen purine nucleoside phosphorylase (PNP). In the absence of phosphate, calf spleen PNP catalyzes a slow hydrolysis of MESG, which is accompanied by inactivation of the enzyme, analogous to the previously observed PNP-catalyzed hydrolysis of inosine and guanosine with formation, in the former case, of a stable PNP·hypoxanthine complex (P.C. Kline and V.L. Schramm (1992) Biochemistry 31, 5964-5973). Qualitative and semiquantitative features of calf spleen PNP- catalyzed hydrolysis of MESG are accounted for by the following model. First, in the absence of phosphate and at pH 7.4, the enzyme exists as an equilibrium mixture of monomer and trimer with a dissociation constant for the trimer of 3 x 1014 M2. Second, a stoichiometric reaction between three molecules of MESG and the PNP trimer results in the formation of a stable PNP·purinethiol complex. Third, the PNP·purinethiol complex initially formed with the monomeric enzyme partitions between product release and formation of a stable complex with 55 turnovers per inactivation event. Fourth, the stable PNP·purinethiol complexes are rapidly dissociated by phosphate to regenerate active enzyme. This dissociation is accompanied by an increase in absorbance at 356 nm consistent with a pK(a) for the purinethiol base on the enzyme of 8.1, compared to a corresponding value of 8.8 in aqueous solution.
Synthesis and evaluation of l-rhamnose 1C-phosphonates as nucleotidylyltransferase inhibitors
Loranger, Matthew W.,Forget, Stephanie M.,McCormick, Nicole E.,Syvitski, Raymond T.,Jakeman, David L.
, p. 9822 - 9833 (2013/10/22)
We report the synthesis of a series of phosphonates and ketosephosphonates possessing an l-rhamnose scaffold with varying degrees of fluorination. These compounds were evaluated as potential inhibitors of α-d-glucose 1-phosphate thymidylyltransferase (Cps2L), the first enzyme in Streptococcus pneumoniae l-rhamnose biosynthesis, and a novel antibiotic target. Enzyme-substrate and enzyme-inhibitor binding experiments were performed using water-ligand observed binding via gradient spectroscopy (WaterLOGSY) NMR for known sugar nucleotide substrates and selected phosphonate analogues. IC 50 values were measured and Ki values were calculated for inhibitors. New insights were gained into the binding promiscuity of enzymes within the prokaryotic l-rhamnose biosynthetic pathway (Cps2L, RmlB-D) and into the mechanism of inhibition for the most potent inhibitor in the series, l-rhamnose 1C-phosphonate.
SYNTHESIS AND RADIOPROTECTANT PROPERTIES OF SULFUR-CONTAINING DERIVATIVES OF NATURAL PURINE METABOLITES
Krutovskikh, G. N.,Gornaeva, G. F.,Vartanyan, L. P.,Muravich-Aleksandr, Kh. L.,Pernikova, V. G.
, p. 493 - 496 (2007/10/02)
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