18354-06-8Relevant articles and documents
Immobilized Drosophila melanogaster deoxyribonucleoside kinase (DmdNK) as a high performing biocatalyst for the synthesis of purine arabinonucleotides
Serra, Immacolata,Conti, Silvia,Piskur, Jure,Clausen, Anders R.,Munch-Petersen, Birgitte,Terreni, Marco,Ubiali, Daniela
, p. 563 - 570 (2014/05/20)
Fruit fly (Drosophila melanogaster) deoxyribonucleoside kinase (DmdNK; EC: 2.7.1.145) was characterized for its substrate specificity towards natural and non-natural nucleosides, confirming its potential in the enzymatic synthesis of modified nucleotides. DmdNK was adsorbed on a solid ion exchange support (bearing primary amino groups) achieving an expressed activity >98%. Upon cross-linking with aldehyde dextran, expressed activity was 30-40%. Both biocatalysts (adsorbed or cross-linked) were stable at pH 10 and room temperature for 24 h (about 70% of retained activity). The cross-linked DmdNK preparation was used for the preparative synthesis of arabinosyladenine monophosphate (araA-MP) and fludarabine monophosphate (FaraAMP). Upon optimization of the reaction conditions (50 mM ammonium acetate, substrate/ATP ratio= 1:1.25, 2 mM MgCl2, 378C, pH 8) immobilized DmdNK afforded the title nucleotides with high conversion (>90%), whereas with the soluble enzyme lower conversions were achieved (78-87%). Arabinosyladenine monophosphate was isolated in 95% yield and high purity (96.5%).
Bisphosphonate derivatives of nucleoside antimetabolites: Hydrolytic stability and hydroxyapatite adsorption of 5′-β,γ-methylene and 5′-β,γ-(1-hydroxyethylidene) triphosphates of 5-fluorouridine and ara-cytidine
Ora, Mikko,Loennberg, Tuomas,Florea-Wang, Diana,Zinnen, Shawn,Karpeisky, Alexander,Loennberg, Harri
, p. 4123 - 4130 (2008/09/21)
(Chemical Equation Presented) Kinetics of the hydrolytic reactions of four bisphosphonate derivatives of nucleoside antimetabolites, viz., 5-fluorouridine 5′-β,γ-(1-hydroxyethylidene) triphosphate (4), 5-fluorouridine 5′-β,γ-methylene triphosphate (5), ara-cytidine 5′-β,γ-(1-hydroxyethylidene) triphosphate (6), and ara-cytidine 5′-β,γ-methylene triphosphate (7), have been studied over a wide pH range (pH 1.0-8.5) at 90°C. With each compound, the disappearance of the starting material was accompanied by formation of the corresponding nucleoside 5′-monophosphate, the reaction being up to 2 orders of magnitude faster with the β,γ-(1-hydroxyethylidene) derivatives (4, 6) than with their β,γ-methylene counterparts (5, 7). With compound 7, deamination of the cytosine base competed with the phosphate hydrolysis at pH 3-6. The measurements at 37°C (pH 7.4) in the absence and presence of divalent alkaline earth metal ions (Mg2+ and Ca2+) showed no sign of metal ion catalysis. Under these conditions, the initial product, nucleoside 5′-monophosphate, underwent rapid dephosphorylation to the corresponding nucleoside. Hydrolysis of the β,γ-methylene derivatives (5, 7) to the corresponding nucleoside 5′-monophosphates was markedly faster in mouse serum than in aqueous buffer (pH 7.4), the rate-acceleration being 5600- and 3150-fold with 5 and 7, respectively. In human serum, the accelerations were 800- and 450-fold compared to buffer. In striking contrast, the β,γ-(1-hydroxyethylidene) derivatives did not experience a similar decrease in hydrolytic stability. The stability in human serum was comparable to that in aqueous buffer (τ1/2 = 17 and 33 h with 4 and 6, respectively), and on going to mouse serum, a 2- to 4-fold acceleration was observed. To elucidate the mineral-binding properties of 4-7, their retention on a hydroxyapatite column was studied and compared to that of zoledronate (1a) and nucleoside mono-, di-, and triphosphates.
17O NMR of Nucleosides. 3 - Chemical Shifts of Substituted Uridines and Ribothymidines
Schwartz, Herbert M.,MacCoss, Malcolm,Danyluk, Steven S.
, p. 885 - 894 (2007/10/02)
Uridine and ribothymidine derivatives, bearing different substituents at C-5 and enriched (Ca 50percent) with 17O in the O-4 and O-2 carbonyls, have been studied via 17O NMR in both acetonitrile and aqueous solvents.The solvent shift differences between acetonitrile and water at O-4 (30-42 ppm) and O-2 (13-16 ppm) vary significantly from each other, but the chemical shift changes induced by changing the substituent at C-5 correlated well only with the O-4 shifts and the electron-withdrawing ability of the substituent.Examination of the 17O shifts of model compounds reconfirms the predominance of keto tautomers for both carbonyls.The significance of the solvent shifts and substituent shifts are discussed with respect to the electronic structure of the nucleoside base rings, and with respect to the hydrogen-bonding abilities of the carbonyl groups.Other nucleoside derivatives studied include those in which the 17O enrichment is in the ring linking the base to the sugar moiety in a pyrimidine cyclonucleoside, in the sugar hydroxy groups and in the phosphodiester linkage of a highly strained ring system in a nucleoside cyclic monophosphate.
