16220-07-8Relevant articles and documents
Recognition of Artificial Nucleobases by E. coli Purine Nucleoside Phosphorylase versus its Ser90Ala Mutant in the Synthesis of Base-Modified Nucleosides
Fateev, Ilja V.,Kharitonova, Maria I.,Antonov, Konstantin V.,Konstantinova, Irina D.,Stepanenko, Vasily N.,Esipov, Roman S.,Seela, Frank,Temburnikar, Kartik W.,Seley-Radtke, Katherine L.,Stepchenko, Vladimir A.,Sokolov, Yuri A.,Miroshnikov, Anatoly I.,Mikhailopulo, Igor A.
, p. 13401 - 13419 (2015)
A wide range of natural purine analogues was used as probe to assess the mechanism of recognition by the wild-type (WT) E. coli purine nucleoside phosphorylase (PNP) versus its Ser90Ala mutant. The results were analyzed from viewpoint of the role of the Ser90 residue and the structural features of the bases. It was found that the Ser90 residue of the PNP 1) plays an important role in the binding and activation of 8-aza-7-deazapurines in the synthesis of their nucleosides, 2) participates in the binding of α-D-pentofuranose-1-phosphates at the catalytic site of the PNP, and 3) catalyzes the dephosphorylation of intermediary formed 2-deoxy-α-D-ribofuranose-1-phosphate in the trans-2-deoxyribosylation reaction. 5-Aza-7-deazaguanine manifested excellent substrate activity for both enzymes, 8-amino-7-thiaguanine and 2-aminobenzothiazole showed no substrate activity for both enzymes. On the contrary, the 2-amino derivatives of benzimidazole and benzoxazole are substrates and are converted into the N1- and unusual N2-glycosides, respectively. 9-Deaza-5-iodoxanthine showed moderate inhibitory activity of the WT E. coli PNP, whereas 9-deazaxanthine and its 2′-deoxyriboside are weak inhibitors. How does it work? The substrate and inhibitory properties of a wide range of artificial bases for the wild-type E. coli purine nucleoside phosphorylase (PNP) versus its Ser90Ala mutant were studied to evaluate the mechanism of recognition by PNP and the role of various electronic and structural features in this process. The PNP recognized a broad palette of bases consisting of a number of dissimilar fragments determining its ability to interact with the Asp204 and Ser90 residues (see scheme).
Enzymatic Synthesis of 2-Deoxyribose 1-Phosphate and Ribose 1 Phosphate and Subsequent Preparation of Nucleosides
Kulikova, Irina V.,Drenichev, Mikhail S.,Solyev, Pavel N.,Alexeev, Cyril S.,Mikhailov, Sergey N.
, p. 6999 - 7004 (2019/11/13)
α-Ribose-1-phosphate (Rib-p) and 2-deoxy-α-ribose-1-phosphate (dRib-p) are key intermediates in nucleoside metabolism and are important starting compounds for the enzymatic synthesis of various modified nucleosides. To date, chemical and enzymatic methods allowed the preparation of these compounds in rather low yields (11–37 %). This prevents their widespread use for the enzymatic synthesis of biologically active and practically important nucleosides. Here we propose to use 7-methyl-2′-deoxyguanosine (7-Me-dGuo) and 7-methylguanosine (7-Me-Guo) for the preparation of dRib-p and Rib-p. In this paper, we present the effective preparation of Rib-p and dRib-p starting from readily prepared 7-methylguanosine derivatives via their irreversible enzymatic phosphorolysis in the presence of purine nucleoside phosphorylase. Rib-p and dRib-P are obtained in nearly quantitative yields (HPLC analysis) and 74–96 % yields after their isolation and purification, which is much higher than previously reported.
Synthesis and biological activity of certain 3,4-disubstituted pyrazolo[3,4-d]pyrimidine nucleosides
Cottam,Petrie,McKernan,Goebel,Dalley,Davidson,Robins,Revankar
, p. 1119 - 1127 (2007/10/02)
A number of 3,4-disubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides were synthesized and tested for their biological activity. Glycosylation of persilylated as well as nonsilylated 3-bromoallopurinol with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose
