Human epigenetic enzyme disruptor of telomeric silencing 1-like (DOT1L) is a key drug target for treating acute myeloid leukemia. Several nucleoside and non-nucleoside DOT1L inhibitors have been developed to inhibit its histone methyltransferase activity. Non-mechanism-based shown good inhibitory activity high on-target residence times. Previous computational studies explored the dynamic behavi...

7-Hydroxyguanine, an antitumor purine-analog, reacted with ribose (or deoxyribose)-1-phosphate in the presence of purine nucleoside phosphorylase. We prepared 7-hydroxyguanine riboside and deoxyriboside using purine nucleoside phosphorylase from bovine spleen. Each nucleoside exhibits antitumor activity against mouse leukemia L1210 cells. The therapeutic effect of 7-hydroxyguanine deoxyriboside...

The synthesis of a pyrazolo[1,5-a]-1,3,5-triazine C-nucleoside (dA(PT)), designed to form two hydrogen bonds with a complementary dT residue, is reported. Oligonucleotides including this dA nucleoside analogue possess base-pairing properties similar to those of the parent oligonucleotide. This dA nucleoside analogue is more resistant to acid-catalyzed hydrolysis than dA.

In contrast to tetrazole, pyridine hydrochloride/imidazole converts nucleoside phosphoramidites to intermediates that show a high preference for phosphitilating hydroxyl groups relative to nucleoside amino groups. Use of this activating agent and incorporation of a pyridine hydrochloride/aniline wash step in the synthetic cycles permit synthesis of mixed base twenty-mer oligonucleotides from nu...

The synthesis and separation of diastereoisomerically pure 5'-O-DMT-nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholane) allows their use as synthons in DBU-catalyzed reaction with the 5'-hydroxyl function of solid-support-bound nucleoside moiety. Since this reaction is stereospecific (greater than 99%), this novel method allows preparation of oligo(nucleoside phosphorothioates) with predetermined...

N-Ribohydrolases, including the inosine-adenosine-guanosine-preferring (IAG) nucleoside hydrolase, have been proposed to be involved in the nucleoside salvage pathway of protozoan parasites and may constitute rational therapeutic targets for the treatment of these diseases. Reported is the complete sequence of the Trypanosoma brucei brucei iagnh gene, which encodes IAG-nucleoside hydrolase. The...

A new nucleoside has been identified in tRNATyr from Escherichia coli MRE 600, where it replaces the highly modified nucleoside queuosine. The nucleoside is also present in a large amount relative to queuosine in mixed tRNA from E. coli strains MRE 600 and W (from which it was isolated for characterization). The new nucleoside has been characterized as an epoxy derivative of queuosine: 7-(5-[(2...

DNA labeling in vivo using nucleoside analogues is a current experimental approach to determine cell proliferation rates in cell cultures and tissues. It has also been successfully used to localize adult stem cell niches through the identification of nucleoside label-retaining cells (LRC) in long-term experiments. A major hindrance of this methodology relies on the selection of adequate procedu...

Bacteriophage phi 6 contains three segments of double-stranded RNA. The procapsid consists of proteins P1, P2, P4, and P7, which are encoded by the viral L segment. cDNA copies of this segment have been cloned into plasmids that direct the production of these proteins, which assemble into polyhedral procapsids. These procapsids are capable of packaging plus-sense phi 6 RNA in the presence of nu...