Cyclo-saligenyl-5-fluoro-2′-deoxyuridinemonophosphate (cycloSal-FdUMP) — A New Prodrug Approach for FdUMP

Abstract

The synthesis of cycloSal-FdUMP 3a-d as a new prodrug approach for FdU 1 is described. Phosphotriesters 3 release the FdUMP 2 selectively by a controlled, chemically induced tandem reaction in hydrolysis studies. The biological activity (IC₅₀) of cycloSal-phosphotriesters 3 was evaluated in FM3A/O cells and FM3A/TK^? cells.     

Investigation of the Synthesis of 2-Carbamoylmethyl-6-D-Ribofuranosylpyridine

Abstract

During the course of our study on the synthesis of new pyridine-C-nucleosides with potential anti-viral and/or anti-tumourai properties, the preparation of 2-carbamoylmethyl-6-β-D-ribofuranosylpyridine 1, by means of a lithiation reaction on 2-(2,3-0-isopropylidene-β D-nbofuranosyl)-6-methylpyridine 2, was investigated (Scheme I). The latter compound was prepared by treating 6-methyl- toluenesulphonic acid. 2-(& D-ribofuranosyl)pyridine 1 2 with 2.2-dimethoxypropane in the presence of p-     

Low Level,Detection of Modified DNA Bases and Nucleosides by FAB MS/MS

Abstract

The identification and quantitation of DNA adducts formed by reaction of genotoxic chemicals with DNA may provide direct evidence of exposure t o mutagens and carcinogens and may make possible a beginning of risk estimation based on Molecular Dosimetry approach.     

Improved Synthesis of 2′,3′-Dideoxycytidine (d2C) and Its Correlated Nucleoside Analogues

Abstract

2′,3′-dideoxy- and 2′,3′-dideoxy-2′,3′-didehydrocy-tidine (d2C and d4C) have been synthesized in good yields from 2′-deoxyuridine via dichlorinated derivatives 7a-b. The same synthetic strategy was used in the synthesis of d2C^Me and d4C^Me from thymidine. Following this method the evaluable 3′-chloro-2′-deoxycytidine derivatives 9-12 can easily be obtained.     

Synthesis and Antiviral Activity of 1,2-Carbonucleosides

Abstract

Members of a new class of carbonucleoside analogues (OTC, o ne t wo substituted c arbonucleosides) were synthesized and evaluated against HIV.     

Therapeutic Implications of The Unusually Long Half-Life of (E)-5–(2–bromovinyl)uracil (Bvura) In Vivo

Abstract

The long half-life of BVUra in the plasma permits, on the one hand, the de novo formation of the antiviral drug (E)-5–(2-bromovinyl)-2′-deoxyuridine (BVdUrd) by a pentosyl transfer, and, on the other hand, the inhibition of the degradation of pyrimidine bases such as 5-fluorouracil (FUra).     

Ribosylation of Pyrimidine 2′-Deoxynucleosides

Abstract

The previously developed method for the preparation of 2′-O-D-ribofuranosyl-nucleosides is extended to ribosylation of 2′-deoxynucleosides. The scope and limitations of this reaction are discussed.     

De Novo Assembly and Functional Annotation of the Olive (Olea europaea) Transcriptome

Olive breeding programmes are focused on selecting for traits as short juvenile period, plant architecture suited for mechanical harvest, or oil characteristics, including fatty acid composition, phenolic, and volatile compounds to suit new markets. Understanding the molecular basis of these characteristics and improving the efficiency of such breeding programmes require the development of genomic information and tools. However, despite its economic relevance, genomic information on olive or closely related species is still scarce. We have applied Sanger and 454 pyrosequencing technologies to generate close to 2 million reads from 12 cDNA libraries obtained from the Picual, Arbequina, and Lechin de Sevilla cultivars and seedlings from a segregating progeny of a Picual × Arbequina cross. The libraries include fruit mesocarp and seeds at three relevant developmental stages, young stems and leaves, active juvenile and adult buds as well as dormant buds, and juvenile and adult roots. The reads were assembled by library or tissue and then assembled together into 81 020 unigenes with an average size of 496 bases. Here, we report their assembly and their functional annotation.     

Age- and gender-related oxidative status determined in healthy subjects by means of OXY-SCORE,a potential new comprehensive index

Oxidative stress has been related to various diseases, gender and ageing, and has been measured by various markers. The authors developed a procedure to compute a global oxidative stress index (OXY-SCORE), reflecting both oxidative and antioxidant markers in healthy subjects. Its performance was tested in relation to age and gender and in coronary artery disease (CAD) patients. Eighty-two healthy subjects and 20 CAD patients were enrolled. Plasma free and total malondialdehyde (F- and T-MDA), glutathione disulphide/reduced form ratio (GSSG/GSH) and urine isoprostanes (iPF_2α-III) levels were combined as oxidative damage markers (damage score). GSH, α- and γ-tocopherol (TH) levels, and individual antioxidant capacity were combined as antioxidant defence indexes (protection score). The OXY-SCORE was computed by subtracting the protection score from the damage score. Among single parameters, T-MDA and iPF_2α-III significantly correlated with age; only GSH and both tocopherols correlated with male gender in healthy subjects. The OXY-SCORE was positively associated with age (p=0.004) and male gender (p=0.03). As expected, the OXY-SCORE was higher in CAD with a very significant p-value (<0.0001), after adjusting for age, gender and smoking. Combining different markers can potentially provide a powerful index in the evaluation of oxidative stress related to age, gender and CAD status.