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D Gasparutto

Publications and source records attributed to D Gasparutto.

24 records · Page 2Linked to original sources

Assessing and counteracting the prooxidant effects of anticancer drugs.

The relationship between peroxide generation and respective cellular damage, triggering various biochemical consequences is first discussed. Then we review the prooxidant effects of various anticancer drugs including anthracyclines and bleomycin, platinum derivatives and the N- and S-mustards. We present and discuss some experimental results on peroxidase inhibition by drugs such as zinc salts, almitrine, deferoxamine, which had previously been tested as efficient in vivo treatment on chlormethine intoxication. In an overview we propose that not only ionizing radiations and anticancer drugs, but also promoters and initiators of cancer might all generate free radicals, in turn triggering oxidative processes generating endogenous peroxides, then probably amplifying the deleterious biological response. The possible limitations of drug therapies decreasing peroxide generation are presented.

Alkylating Agents↗

[Total chemical synthesis of natural transfer RNA].

New improvements in the chemical synthesis of oligoribonucleotides are reported and they are applied to the first total chemical synthesis of a natural RNA. This E. coli K12 alanine tRNA contains in its sequence dihydrouridine, ribothymidine and pseudo-uridine. The synthetic tRNA was fully sequenced and showed a 42% aminoacyl acceptance activity. When tRNA was used as a template, reverse transcriptase directed the incorporation of adenine opposite dihydrouridine, ribothymidine and pseudouridine.

Base Sequence↗

Labile protecting groups in tRNA synthesis.

The use of labile protecting groups for the protection of the exocyclic amino function of adenine, guanine and cytosine has two main advantages in RNA synthesis. Final deprotection in concentrated aqueous ammonia takes place in milder conditions which are more compatible with the sensitivity of oligoribonucleotides towards alkali-conditions. The introduction of fragile bases such as certain modified bases encountered in the primary structure of t-RNA is feasible. The chemical synthesis of RNA fragments constituting the primary structure of B. subtilis f-methionine t-RNA is described.

Bacillus subtilis↗

5-(phenylthiomethyl)-2'-deoxyuridine as an efficient photoreactive precursor to generate single and multiple lesions within DNA fragments.

5-(Phenylthiomethyl)-2'-deoxyuridine was successfully incorporated into DNA oligomers by automated DNA synthesis using phosphoramidite chemistry. UV exposure of the latter thionucleoside containing oligonucleotides under anaerobic and aerobic conditions gives rise to specific base lesions. The photoproducts have been isolated and further characterized on the basis of NMR and mass spectrometric analyses.

DNA↗

New synthesis of 5-carboxy-2'-deoxyuridine and its incorporation into synthetic oligonucleotides.

5-Carboxy-2'-deoxyuridine is a methyl oxidation product of thymidine. It can be formed by the menadione-mediated photosensitization of thymidine in aerated aqueous solution. Here in we present a new four-step synthesis of the 5-carboxy-2'-deoxyuridine phosphoramidite building block based on the alkaline hydrolysis of 5-trifluoromethyl-2'-deoxyuridine. The phosphoramidite derivative has been incorporated at defined sites into oligonucleotides using the solid phase synthesis approach.

Amides↗

MALDI-TOF mass spectrometry as a powerful tool to study enzymatic processing of DNA lesions inserted into oligonucleotides.

MALDI-TOF mass spectrometry measurements, coupled with either exonuclease or DNA N-glycosylases digestions of lesion-containing oligonucleotides, were used to assess biochemical features of several oxidative DNA damage. The latter analytical approach was shown to be an informative and efficient alternative technique to conventional electrophoresis and chromatographic analyses.

Animals↗