A5075310386- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- Fluorine in Organic Chemistry
- Synthesis and Characterization of Heterocyclic Compounds
- Cytomegalovirus and herpesvirus research
- Chemical Synthesis and Analysis
- Adenosine and Purinergic Signaling
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and biological activity
- Peptidase Inhibition and Analysis
- Synthesis and Reactions of Organic Compounds
- Folate and B Vitamins Research
- Synthesis of Organic Compounds
- Chronic Lymphocytic Leukemia Research
- Enzyme Structure and Function
- RNA Interference and Gene Delivery
- Acute Lymphoblastic Leukemia research
- Quinazolinone synthesis and applications
- Pneumocystis jirovecii pneumonia detection and treatment
National Academy of Sciences of Belarus
2011-2024
Institute of Bioorganic Chemistry
2011-2024
Technische Universität Berlin
2015
Ministry of Economy of the Republic of Belarus
2010
Veterans Health Administration
2009
University of Eastern Finland
2004-2008
Frederick National Laboratory for Cancer Research
2008
National Institutes of Health
2008
National Cancer Institute
2008
Osnabrück University
1993-2007
A survey of the chemo-enzymatic methodology for preparation nucleosides biological importance is presented. The emphasis made on enzymatic transglycosylation and glycosylation employing nucleoside phosphorylases N-deoxyribosyltransferases. Application whole cells as biocatalysts well purified enzymes from wild-type bacteria recombinant considered. Keywords: N-Deoxyribosyltransferases, deoxyribosyltransferase, Nucleoside Phosphorylases, Escherichia coli, cytidine deaminase (CDase)
This review focuses on new trends in nucleoside biotechnology, which have emerged during the last decade. Continuously growing interest study of this class compounds is fueled by a number factors: (i) need for large-scale production natural 2'-deoxy-β-D-ribonucleosides as well their analogs with modifications carbohydrate and base fragments, can then be used synthesis oligonucleotides, including short-interfering RNA (siRNA), microRNA (miRNA), etc.; (ii) necessity development efficient...
Thermostable nucleoside phosphorylases are attractive biocatalysts for the synthesis of modified nucleosides. Hence we report on recombinant expression three 'high molecular mass' purine (PNPs) derived from thermophilic bacteria Deinococcus geothermalis, Geobacillus thermoglucosidasius and hyperthermophilic archaeon Aeropyrum pernix (5'-methythioadenosine phosphorylase; ApMTAP). Thermostability studies, kinetic analysis substrate specificities reported. The PNPs were stable at their optimal...
Abstract The enzymatic transglycosylation of 2,6‐dichloropurine (26DCP) and 6‐chloro‐2‐fluoropurine (6C2FP) with uridine, thymidine 1‐(β‐ D ‐arabinofuranosyl)‐uracil as the pentofuranose donors recombinant thermostable nucleoside phosphorylases from G. thermoglucosidasius or T. thermophilus biocatalysts was studied. Selection 26DCP 6C2FP substrates is determined by their higher solubility in aqueous buffer solutions compared to most natural modified purines and, furthermore, synthesized...
A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides natural heterocyclic bases have been synthesized with the use universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic antiviral activity compounds was evaluated against a variety tumor cell lines DNA/RNA viruses, As most active compound, from both viewpoint,...
Two approaches to the synthesis of 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine ( 1 , clofarabine) were studied. The first approach consists in chemical 2-deoxy-2-fluoro-α-D-arabinofuranose-1-phosphate 12a 2F Ara-1P) via three step conversion 1,3,5-tri- O -benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose 9 ) into phosphate without isolation intermediary products. Condensation with 2-chloroadenine catalyzed by recombinant E. coli purine nucleoside phosphorylase (PNP) resulted...
Abstract A wide range of natural purine analogues was used as probe to assess the mechanism recognition by wild‐type (WT) E. coli nucleoside phosphorylase (PNP) versus its Ser90Ala mutant. The results were analyzed from viewpoint role Ser90 residue and structural features bases. It found that PNP 1) plays an important in binding activation 8‐aza‐7‐deazapurines synthesis their nucleosides, 2) participates α‐ D ‐pentofuranose‐1‐phosphates at catalytic site PNP, 3) catalyzes dephosphorylation...
The conformations of three 2',3'-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that two vicinal fluorine atoms play puckering preferences furanose ring. Two compounds examined contained either arabino or xylo dispositions at C2' C3' a 2',3'-dideoxyuridine system. third compound also incorporated configuration on ring but was substituted with 6-azauracil base place uracil. A battery...
The synthesis of methyl 5-O-benzoyl-2-chloro-2,3-dideoxy-3-fluoro-beta-d-ribofuranoside (5) and its use as a glycosylating agent for persilylated thymine, N(6)-benzoyladenine, N(4)-benzoylcytosine are described (Scheme 1). 2'-chloro-2',3'-dideoxy-3'-fluoro-d-ribonucleosides 10-12 synthesized were transformed to 2',3'-dideoxy-3'-fluoro-alpha- -beta-d-erythro-pentofuranoside nucleosides thymine (13a,b), adenine (14a,b), cytidine (15a,b) by treatment with tributyltin hydride in the presence...
The E. coli BMT-4D/1A cells have been selected according to Munch-Petersen et al. They carry two regulatory mutations (cytR and deoR) are able synthesize constitutively nucleoside-catabolizing enzymes, e.g., that possess high UPase PNPase activities. cross-linked by glutaraldehyde afford a biocatalyst retained activities was comfortable for repeated use. An incubation of 2′-deoxyguanosine (1) 2-chloroadenine (2) (molar ratio 3 : 1) in K-phosphate buffer (10 mM; pH 7.0) the presence at 65° 7...
Abstract Structural correlations have been carried out from 13 C chemical shifts (δ) and by analysis of 1 J (CH) coupling constants, the conformation about glycosidic bond has studied means 3 vicinal constants between C‐8 H‐1′ some adenine nucleosides such as adenosine (Ado), N (7)‐β‐D‐ribofuranosyladenine ( (7)‐Ado), (9)‐ (7)‐β‐D‐xylofuranosyladenine (9)‐xylAde (7)‐xylAde), (9)‐(3‐chloro‐3‐deoxy‐β‐D‐xylofuranosyl)adenine (3′‐Cl‐xylAde) (9)‐(2‐chloro‐2‐deoxy‐β‐D‐arabinofuranosyl)adenine...
The reaction of (diethylamino)sulfur trifluoride (DAST) with methyl 5-O-benzoyl-β-D-xylofuranoside (1) followed by column chromatography afforded the riboside 2 (62%) and ribo-epoxide 3 (18%) (Scheme 1). Under similar conditions, α-D-anomer 4 gave 5 difluoride 6 in 60 9% yield, respectively. Treatment β-D-xyloside 10 DAST gave, after chromatographic purification, 11 as principal product (48%; Scheme 2). These results suggest that C(3)−O−SF2NEt2 derivatives were initially formed case...
A convenient preparation of the 9-ß-D-xylofuranosides adenine (xylo-A) and guanine (xylo-G) is described. 1,2-Di-O-acetyl-3,5-Di-O-(p-nitrobenzoyl)-D-xylofuranose used as glycosylating agent a modified procedure for its given. The method stereospecific ß-anomers.
The enzymatic synthesis of 8-azapurine and 8-aza-7-deazapurine 2′-deoxyribonucleosides has been studied. Two methods have used: (i) transglycosylation employing 2′-deoxyguanosine, 2′-deoxycytidine, 2′-deoxyuridine, 2′-deoxythymidine as 2-deoxy-<sc>d</sc>-ribofuranose donors recombinant <i>E. coli</i> purine nucleoside phosphorylase (PNP) biocatalyst, (ii) one-pot from 2-deoxy-<sc>d</sc>-ribose nucleobases ribokinase (RK), phosphopentomutase (PPM) PNP biocatalysts. Good substrate activity was...
The conformation of the 7-bromo- and 7-iodo-substituted 8-aza-7-deazapurine nucleosides 1 2 in solid state aqueous solution was studied by single-crystal X-ray analyses 1H-NMR spectroscopy. In state, both compounds display a high-anti around glycosylic bond, their 2′-deoxy-β-D-ribofuranose moieties adopt an N-type sugar puckering. orientation exocyclic C(4′)−C(5′) bond found to be ap cases. D2O solution, i) 8 – 10% higher N-conformer population than 2′-deoxyguanosine ii) preference −sc about...