84-82-2Relevant articles and documents
Biochemical Characterization and Structural Basis of Reactivity and Regioselectivity Differences between Burkholderia thailandensis and Burkholderia glumae 1,6-Didesmethyltoxoflavin N-Methyltransferase
Fenwick, Michael K.,Almabruk, Khaled H.,Ealick, Steven E.,Begley, Tadhg P.,Philmus, Benjamin
, p. 3934 - 3944 (2017)
Burkholderia glumae converts the guanine base of guanosine triphosphate into an azapteridine and methylates both the pyrimidine and triazine rings to make toxoflavin. Strains of Burkholderia thailandensis and Burkholderia pseudomallei have a gene cluster encoding seven putative biosynthetic enzymes that resembles the toxoflavin gene cluster. Four of the enzymes are similar in sequence to BgToxBCDE, which have been proposed to make 1,6-didesmethyltoxoflavin (1,6-DDMT). One of the remaining enzymes, BthII1283 in B. thailandensis E264, is a predicted S-adenosylmethionine (SAM)-dependent N-methyltransferase that shows a low level of sequence identity to BgToxA, which sequentially methylates N6 and N1 of 1,6-DDMT to form toxoflavin. Here we show that, unlike BgToxA, BthII1283 catalyzes a single methyl transfer to N1 of 1,6-DDMT in vitro. In addition, we investigated the differences in reactivity and regioselectivity by determining crystal structures of BthII1283 with bound S-adenosylhomocysteine (SAH) or 1,6-DDMT and SAH. BthII1283 contains a class I methyltransferase fold and three unique extensions used for 1,6-DDMT recognition. The active site structure suggests that 1,6-DDMT is bound in a reduced form. The plane of the azapteridine ring system is orthogonal to its orientation in BgToxA. In BthII1283, the modeled SAM methyl group is directed toward the p orbital of N1, whereas in BgToxA, it is first directed toward an sp2 orbital of N6 and then toward an sp2 orbital of N1 after planar rotation of the azapteridine ring system. Furthermore, in BthII1283, N1 is hydrogen bonded to a histidine residue whereas BgToxA does not supply an obvious basic residue for either N6 or N1 methylation.
Convenient synthesis of toxoflavin that targets β-catenin/TCF4 signaling activities
Mao, Yongjun,Tian, Wang,Huang, Ziwei,An, Jing
, p. 594 - 597 (2014/06/10)
A rapid and improved route for synthesis of toxoflavin, an antibiotic and antitumor agent, is described. The method uses easily obtained materials and simple and practical reactions, including chlorination, condensation, and diazotization to produce toxoflavin in five steps with 14.2% yield and 98.6% purity (HPLC). This synthetic toxoflavin effectively inhibited β-catenin/Tcf4 driven TOP-luciferase activity with an IC50 of less than 0.5 μM and induced colon cancer cell death in a dose-dependent manner with an IC50 of 0.29 μM.
The facile synthesis of 6-azapurines by transformation of toxoflavins (7-azapteridines)
Nagamatsu, Tomohisa,Ma, Jun,Yoneda, Fumio
body text, p. 849 - 854 (2010/10/03)
This paper describes a reliable and facile synthesis of 6-azapurines (1,5-dimethyl-1H imidazo[4,5-e][1,2,4]triazin-6(5H)-ones) by treatment of toxoflavins (7-azapteridines) with 10% aqueous sodium hydroxide at 5-25 °C along with a benzilic acid type rearr
