Disease relevance of THIOGUANOSINE

• Dynamics of RNA-protein interactions in the HIV-1 Rev-RRE complex visualized by 6-thioguanosine-mediated photocrosslinking [1].
• BACKGROUND & AIMS: Azathioprine is the gold standard for immunosuppressive therapy in Crohn's disease (CD) and its molecular mechanism of action is caused by the metabolite 6-thioguanosine triphosphate (TGTP) [2].

High impact information on THIOGUANOSINE

• 6-TG given alone reduced GTP levels and DNA synthesis rates in HL-60 cells, while a major intracellular 6-TG metabolite, 6-thioguanosine 5'-monophosphate, accumulated to high levels (approximately 100 microM) [3].
• Measurement of PRPP amidotransferase activity using cell homogenates revealed altered kinetics for the enzyme from TGuo-30-2 cells, which included significant loss of sensitivity to feedback inhibition by 6-thioguanosine 5'-phosphate and greater catalytic activity at low concentrations of PRPP [4].
• During incubation with TG, the monophosphorylated form of thioguanosine was transported by both MRP4 and MRP5; the highest transport rate was for MRP4 [5].
• In contrast, induction of TPMT produced a 1.6-fold decrease in sensitivity to 6-TG, a decrease in levels of DNA-TGN, and an increase in levels of methylated thioguanosine monophosphate [6].
• Here, we present results of photocross-linking analysis of native and minimal hammerheads containing photoreactive nucleobases 6-thioguanosine, 2,6-diaminopurine, 4-thiouridine, and pyrrolocytidine, introduced at specific sites within the catalytic core [7].

Biological context of THIOGUANOSINE

• We have used a site-specific photocrosslinking method based on 6-thioguanosine (6-thioG) photochemistry to probe the conformation of the high-affinity binding site of RRE RNA and its interactions with Rev protein under physiological conditions [1].
• Investigation of 6-thiodeoxyguanosine alkylation products and their role in the potentiation of BCNU cytotoxicity [8].
• The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VII. Chemical synthesis by phosphorylation of 6-thioguanosine 5'-monophosphate, 5'-diphosphate and 5'-triphosphate, and their purification and identification by reversed-phase/ion-pair high-performance liquid chromatography and by various enzymatic assays [9].

Anatomical context of THIOGUANOSINE

• A fluorescent derivative of 6-mercaptoguanosine, S-(N-dansylaminoethyl)-6-mercaptoguanosine, was synthesized, and found to be a strong inhibitor of the uridine transport system of erythrocyte (Ki approximately 0.3 microM) [10].
• Magnesium ion dependent rabbit skeletal muscle myosin guanosine and thioguanosine triphosphatase mechanism and a novel guanosine diphosphatase reaction [11].
• The newly synthesized DNA of HeLa cells containing thioguanosine, adsorbed specifically on an organomercurial agarose column and was eluted with 2-mercaptoethanol [12].

Associations of THIOGUANOSINE with other chemical compounds

• The interaction of a series of chromophoric nucleotides derived from 6-mercapto-9-beta-ribofuranosylpurine (thioinosine, thiol) and 2-amino-6-mercapto-9-beta-ribofuranosyl-purine (thioguanosine, thioG) with myosin subfragment 1 isolated from rabbit skeletal muscle was investigated kinetically and spectroscopically [13].
• This study describes approaches for stacking a large volume of sample solutions containing a mixture of mercaptopurine monohydrate, 6-methylmercaptopurine, thioguanine, thioguanosine, and thioxanthine in capillary electrophoresis (CE) [14].
• One method using a strong anion exchange column allows detection of 6-thioguanosine di- and triphosphate (thioguanine nucleotides) in red blood cells (RBC) with a sensitivity of 30 pmol/100 microliters RBC [15].

Gene context of THIOGUANOSINE

• We have used a site-specific cross-linking method based on 6-thioguanosine (6-thioG) photochemistry to determine the conformation of TAR RNA and its interaction with Tat protein under physiological conditions [16].
• Reassessment of the interactions of guanylate kinase and 6-thioguanosine 5'-phosphate [17].
• Both mercaptopurine and thioguanine are substrates for hypoxanthine-guanine phosphoribosyltransferase and are converted into the ribonucleotides 6-thioguanosine monophosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) respectively [18].
• The intracellular metabolism of 6-MP to 6-thioguanosine nucleotides (TGN) via 6-thioinosine 5'-monophosphate (TIMP) is crucial for its cytotoxic effect [19].
• 6-Thioguanosine phosphoramidite was prepared, using 2,4-dinitrophenyl as protection group for thio-function, and its stability towards conditions of RNA synthesis was investigated [20].

Analytical, diagnostic and therapeutic context of THIOGUANOSINE

• Following from this, a new method is described for the affinity chromatography of thiol-containing molecules and of RNA containing incorporated 6-thioguanosine on columns of mercurated cellulose [21].
• Synthesis of 4-thiouridine, 6-thioinosine, and 6-thioguanosine 3',5'-O-bisphosphates as donor molecules for RNA ligation and their application to the synthesis of photoactivatable TMG-capped U1 snRNA fragments [22].
• Cellulose thin layer chromatography revealed that the radioactive peak of the hydrolysate corresponded to 6-thioguanosine [23].
• Proteins synthesised after treatment of cells with 6-thioguanosine are less stable than proteins synthesised after treatment of cells with 4-thiouridine [24].

References