The patent presents 140 purine and 7-azapurine derivatives as potent inhibitors of DOT1L histone methyltransferase that might be useful in the treatment of leukemia with MLL rearrangements. It is becoming more and more evident that the deregulation of chromatin modifiers such as DOT1L plays a critical role in tumorigenesis. As yet, the number of pharmaceutical agents targeting chromatin modifie...

Treatment of toyocamycin or sangivamycin with 1,3-dibromo-5,5-dimethylhydantoin in MeOH (r.t./30 min) gave 8-bromotoyocamycin and 8-bromosangivamycin in good yields. Nucleophilic aromatic substitution of 8-bromotoyocamycin with sodium azide provided novel 8-azidotoyocamycin. Strain promoted click reactions of the latter with cyclooctynes resulted in the formation of the 1,2,3-triazole products....

Studies on the biosynthesis of the 7-deazaadenine base of the antibiotic, tubercidin, in growing cultures of Streptomyces tubercidicus are described. Isotope incorporation patterns suggest that the pyrimido moiety of a purine serves as the precursor of the pyrimido portion of 7-deazaadenine and that carbon atoms 1 and 2 of ribose may be incorporated into the pyrrole moiety of 7deazaadenine. The...

Oligonucleotides incorporating the 7-propynyl derivatives of 8-aza-7-deaza-2'-deoxyguanosine (3b) and 8-aza-7-deaza-2'-deoxyadenosine (4b) were synthesized and their duplex stability was compared with those containing the 5-propynyl derivatives of 2'-deoxycytidine (1) and 2'-deoxyuridine (2). For this purpose phosphoramidites of the 8-aza- 7-deazapurine (pyrazolo[3,4-d]pyrimidine) nucleosides w...

RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-~H]-7 methylbenz[a]anthracene or [G-:'H]-7-methylbenz[a]anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantit ies of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz[a]anthracene ...

Cell-free preparations from Rhodotorula glutinis catalyzed the conversion of deoxyribonucleosides to ribonucleosides in a pyrimidine deoxyribonucleoside 2' -hydroxylase reaction. The reaction occurred with only thymidine or deoxyuridine, of the common deoxyribonucleosides, without detachment of the deoxyribose moiety, at the nucleoside level. The same enzyme preparations catalyzed the conversio...

7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg(2+)-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5'-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To prov...