4594-45-0Relevant articles and documents
Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase
Hatano, Akihiko,Wakana, Hiroyuki,Terado, Nanae,Kojima, Aoi,Nishioka, Chisato,Iizuka, Yu,Imaizumi, Takuya,Uehara, Sanae
, p. 5122 - 5129 (2019/10/05)
Unnatural nucleosides are attracting interest as potential diagnostic tools, medicines, and functional molecules. However, it is difficult to couple unnatural nucleobases to the 1′-position of ribose in high yield and with β-regioselectivity. Purine nucleoside phosphorylase (PNP, EC2.4.2.1) is a metabolic enzyme that catalyses the conversion of inosine to ribose-1α-phosphate and free hypoxanthine in phosphate buffer with 100% α-selectivity. We explored whether PNP can be used to synthesize unnatural nucleosides. PNP catalysed the reaction of thymidine as a ribose donor with purine to produce 2′-deoxynebularine (3, β form) in high conversion (80%). It also catalysed the phosphorolysis of thymidine and introduced a pyrimidine base with a halogen atom substituted at the 5-position into the 1′-position of ribose in moderate yield (52-73%), suggesting that it exhibits loose selectivity. For a bulky purine substrate [e.g., 6-(N,N-di-propylamino)], the yield was lower, but addition of a polar solvent such as dimethyl sulfoxide (DMSO) increased the yield to 74%. PNP also catalysed the reaction between thymidine and uracil possessing a large functional fluorescent group, 5-(coumarin-7-oxyhex-5-yn) uracil (C4U). Conversion to 2′-deoxy-[5-(coumarin-7-oxyhex-5-yn)] uridine (dRC4U) was drastically enhanced by DMSO addition. Docking simulations between dRC4U and E. coli PNP (PDB 3UT6) showed the uracil moiety in the active-site pocket of PNP with the fluorescent moiety at the entrance of the pocket. Thus, the bulky fluorescent moiety has little influence on the coupling reaction. In summary, we have developed an efficient method for producing unnatural nucleosides, including purine derivatives and modified uracil, using PNP.
Biotransformation of halogenated nucleosides by immobilized Lactobacillus animalis 2′-N-deoxyribosyltransferase
Britos, Claudia N.,Lapponi, María José,Cappa, Valeria A.,Rivero, Cintia W.,Trelles, Jorge A.
, p. 91 - 96 (2016/05/10)
An immobilized biocatalyst with 2′-N-deoxyribosyltransferase (NDT) activity, Lactobacillus animalis NDT (LaNDT), was developed from cell free extracts. LaNDT was purified, characterized and then immobilized by ionic interaction. Different process parameters were optimized, resulting in an active derivative (2.6 U/g) able to obtain 1.75 mg/g of 5-fluorouracil-2′-deoxyriboside, an antimetabolite known as floxuridine, used in gastrointestinal cancer treatment. Furthermore, immobilized LaNDT was satisfactorily used to obtain at short reaction times other halogenated pyrimidine and purine 2′-deoxynucleosides such as 6-chloropurine-2′-deoxyriboside (4.9 U/g), 6-bromopurine-2′-deoxyriboside (4.3 U/g), 6-chloro-2-fluoropurine-2′-deoxyriboside (5.4 U/g), 5-bromo-2′-deoxyuridine (2.8 U/g) and 5-chloro-2′-deoxyuridine (1.8 U/g) compounds of pharmaceutical interest in antiviral or antitumor treatments. Besides, increasing the biocatalyst amount 8 times per volume unit allowed obtaining a 5-fold improvement in floxuridine biotransformation. The developed biocatalyst proved to be effective for the biosynthesis of a wide spectrum of nucleoside analogues by employing an economical, simple and environmentally friendly methodology.
Synthesis and biological evaluation of nucleoside analogues having 6-chloropurine as anti-SARS-CoV agents
Ikejiri, Masahiro,Saijo, Masayuki,Morikawa, Shigeru,Fukushi, Shuetsu,Mizutani, Tetsuya,Kurane, Ichiro,Maruyama, Tokumi
, p. 2470 - 2473 (2008/02/13)
Nucleoside analogues that have 6-chloropurine as the nucleobase were synthesized and evaluated for anti-SARS-CoV activity by plaque reduction and yield reduction assays in order to develop novel anti-SARS-CoV agents. Among these analogues, two compounds,
