Aminonucleosides and their derivatives. IV. Synthesis of the 3'-amino-3'-deoxynucleoside 5'-phosphates.

A new procedure has been developed for the synthesis of 3'-amino-3'-deoxyribonucleosides of adenine, cytosine and uracil by condensing the trimethylsilylated bases with peracylated 3-azido-3-deoxyribose derivative. The azido group could subsequently be reduced to amino. The 5'-phosphates of these nucleosides have been prepared and the analogues have been tested for their ability to stimulate the ribosome-catalyzed reaction of 3'(2')-O-(N-formylmethionyl) adenosine 5'-phosphate with phenylalanyl-tRNA.     

Disaccharide Nucleosides And Their Enzymatic And Chemical Incorporation Into Oligonucleotides

Abstract

A high yield synthesis of different O-ribofuranosylnucleosides has been achieved. Kinetics of the acid-catalysed hydrolysis of disaccharide nucleosides has been studied. Chemical and enzymatic incorporation of 2′-O-ribofuranosyl-nucleoside residue into oligonucleotides was investigated.     

Association of polymorphisms of the CYP1A1 and CYP1A2 cytochrome P450 genes with chronic obstructive pulmonary disease in Bashkortostan

The frequencies of polymorphisms of CYP1A1 (2455A/G, 3801T/C) and CYP1A2 (?2464T/delT, ?163C/A) were determined in healthy residents of Bashkortostan (Russians, Tatars, and Bashkirs) and tested for association with chronic obstructive pulmonary disease (COPD). Interethnic differences in the frequency distribution of the CYP1A1 and CYP1A2 polymorphisms were significant. In Tatars and Russians, the CYP1A1 and CYP1A2 haplotype frequencies were similar (χ² = 0.973, df = 3, P = 1.00 and χ² = 1.546, df = 3, P = 0.92, respectively). In Bashkirs, the CYP1A1 haplotype frequencies significantly differed from those in Russians and Tatars (χ² = 12.328, df = 3, P = 0.008 and χ² = 9.218, df = 3, P = 0.034, respectively) owing to a high frequency of CYP1A1*2B (10.17%). Similarly, Bashkirs differed from Russians and Tatars in the CYP1A2 haplotype frequencies (χ² = 18.779, df = 3, P = 0.0001 and χ² = 14.326, df = 3, P = 0.003, respectively). The frequency of the CYP1A2*1D haplotype in Bashkirs was 11.02% in contrast to 2.36% in Tatars and 1.61% in Russians. Allele *D of the CYP1A2 ?2467delT polymorphism was associated with COPD in Tatars (OR = 1.83, 95%CI 1.24–2.71, χ² = 9.48, P = 0.003). CYP1A2*1D was associated with an increased risk of COPD (8.65% vs. 2.36% in controls, χ² = 9.733, P = 0.0027, P _cor = 0.008, OR = 3.908, 95%CI 1.56–10.19). Haplotype CYP1A2*1A was significantly less frequent in patients with COPD (21.05% vs. 30.74%, χ² = 6.319, P = 0.0127, P _cor = 0.038, OR = 0.6012, 95%CI 0.402–0.898). The CYP1A1 polymorphisms were not associated with COPD in residents of Bashkortostan.     

Synthesis of Dioxolane Analogues of Dideoxynucleotides and Their Substrate Properties in DNA Synthesis Reactions

Abstract

Dioxolane derivatives of dNTP were prepared and their substrate properties were investigated in DNA synthesis reactions.     

Long non‐coding RNAs in melanoma

Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment.     

Analysis of the Polymorphic Markers within the CFTR Gene in Cystic Fibrosis Patients and Healthy Donors from Bashkortostan

The differences in the polymorphic allele frequency distribution patterns of the biallelic (M470V and TUB20) and microsatellite (IVS6aGATT, IVS8CA, and IVS17CA) markers within the CFTR gene between normal and delF508 chromosomes have been established. For most of the marker loci similar distribution of the allele frequencies on normal and mutant chromosomes without delF508 was demonstrated. Certain polymorphic alleles displayed substantial linkage disequilibrium with the delF508 mutation. Analysis of the IVS6aGATT-IVS8CA-M470V-IVS17CA-TUB20 haplotypes association on normal and mutant chromosomes provided identification of the delF508 ancestral haplotype. It was suggested that delF508 mutant chromosomes were introduced into the modern Bashkir gene pool as a result of Slavic migrations from the Eastern Europe. The IVS6aGATT-IVS8CA-M470V-IVS17CA-TUB20major haplotype (77272) revealed was statistically significantly most frequently found on the mutant chromosomes without the delF508 mutation. This finding suggests that the Bashkir cystic fibrosis patients, mostly belonging to the Turkic-speaking families, possessed specific CFTR gene defect associated with the given haplotype.     

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats

Background

The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl₄) in rats.

Results

The animals were divided into four groups with six rats in each group. CCl₄ (0.125 mL kg^-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg^-1 body wt.) was given by gavage 7 days before the CCl₄ injection. Bixin prevented the liver damage caused by CCl₄, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl₄ by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment.

Conclusion

Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl₄ is related to the antioxidant activity of the compound.     

Synthesis of Four Stereoisomers of Carbocyclic 5′-NOR D4A and Evaluation of Their Triphosphates as Substrates for DNA Polymerases

Abstract

A method was developed for synthesis of the four stereoisomeric enantiomerically pure 5′-nor carbocyclic nucleosides 4b, ent-4b, 10 and ent-10 starting from the common enantiomerically pure allylic monoacetate 1. Nucleoside analogues were converted to the corresponding triphosphate derivatives 6, ent-6, 12, and ent-12. The substrate properties of the latters towards different DNA polymerases were evaluated.