Synthese de la Desamino 9’ Sinefungine

Abstract

La sinéfungine dont nous avons récemment achevé la synthèse (1) possède une activité antiparasitaire en particulier sur différentes souches de Leishmania (2) mais présente 1′inconvénient d'ine toxicité non négligeable; nous avons donc entrepris la synthèse d'analogues, en particulier du dérivé 9’ désamino è partir de l'adénosine et è partir du ribose.     

Resistance Profiles of (+) 2′-Deoxy-3′-oxa-4′-thiocytidine and (-) 2′-Deoxy-3′-oxa-4′-thio-5-fluorocytidine

Abstract

Resistant variants were selected in vitro against two novel nucleoside analogues, (+) dOTC and (-) dOTFC using the HIV-1 molecular clone HXB2D. The variants obtained displayed 6.5-fold and 10-fold resistance to these compounds, respectively. Cloning and sequencing of the RT genes of the selected viruses identified two mutations, M184I for (+) dOTC and M184V for (-) dOTFC. Results with mutated recombinant clones of HXB2D confirmed the importance of these mutations in MT-4 cells. The resistance profiles of clinical samples with wild-type or 3TC-resistant phenotypes were also studied; low to moderate levels of cross-resistance were observed against the novel compounds.     

Metabolisme Cutane de la Iodo-5-desoxy-2′-cytidine (IDC)

Abstract

We studied the cutaneous metabolism of the antiherpetic IDC comparatively in mouse and humans. Our results show that tissue deaminating activity is approximatively 13 to 15 times weaker for skin than for kidney homogenates.     

Pour une approche « neurocognitive « de la mémoire: apport de la neuropsychologie

Cognitive models suggest that memory consists of potentially independant modules. In addition, clinical data lead to a reference to the central systems that interact with these operative modules, and which assign significance and pertinence to the information being processed. Such an organization fits better with clinicial data, since it can be demonstrated with the example of episodic or procedural memories as both require the activation of strategic processes, under the control of the prefrontal cortex, needed for the organization or the control of the information to be processed.     

Stéréosélectivité de la réduction de la 3′, 5′-di-O-benzoyl-2′-bromo-2′-désoxyuridine par l'hydrure de tributylétain

Samples of sodium alginate from Laminaria digitata were oxidised in aqueous solution to different extents by the addition of calculated amounts of sodium metaperiodate. An empirical measure of the molecular stiffness of the products, both before and after reduction with sodium borohydride, was obtained by studying the sensitivity of their intrinsic viscosities to changes in the ionic strength of the solution. The results showed that, whereas the stiffness decreased very sharply with increasing degree of oxidation, it changed very little upon subsequent reduction of the products. From this, and the known structures of the inter-residue hemiacetals in the unreduced products, it was inferred that the increase in flexibility brought about by oxidation is specifically associated with rotation about the three bonds adjoining C-4, C-5, the original ring-oxygen atom, and C-1 of the oxidised hexuronic-acid residues. This rotation was considerably less-hindered than the rotation around the glycosidic linkage in both the intact alginate and in the partially oxidised and reduced products. The conversion of only a small percentage of the stiff pyranoid rings into these centres of high, local flexibility had a marked effect on the overall flexibility of the chains, showing that the possible presence of such centres should be taken into account in any discussion of the solution properties of heteropolysaccharides or of polysaccharides that may have suffered slight chemical modification.     

The 5′-Purine-Pyrimidine-3′ Stacks are More Stabilizing in a Self-3′-Pyrinudine-Purine-5′ complementary DNA Duplex than the 5′-Purine-Purine-3′ 3′-Pyrimidine-Pyrimidine-5′ Stack

Abstract

First experimental evidence is herein reported supporting the earlier quantum chemical calculations that 5′-Punne-pyrimiidine-3′ 3′ -Pyrimidine-Punne-5 stack is more stable than 5′-Pyrimiidine-Punne-3′ 3′-Punne-Pyrimidine-5′.     

Synthesis and biophysical properties of 5′-thio-2′,4′-BNA/LNA oligonucleotide

Phosphorothioate modification of oligonucleotides is one of the most promising chemical modifications in nucleic acid therapeutics. Structurally similar 5′-thio or phosphorothiolate-modified nucleotides, in which the 5′-bridging oxygen atom is replaced with a sulfur atom, are attracting attention and gaining importance in oligonucleotide-based research. In our present study, we synthesized 5′-thio-2′,4′-BNA/LNA monomers bearing thymine or 5-methylcytosine nucleobase. The 5′-thio-2′,4′-BNA/LNA monomers were successfully incorporated into target oligonucleotides, and their nuclease stability and binding affinity with complementary strands were evaluated.     

3′-3′,3′-5′ and 5′-5′ TpT-Amides: Synthesis,Characterization and Alkaline Hydrolysis

Abstract

A simple procedure is described for the preparation of the title compounds 1, 8 and 9. 3′-3′ or 3′-5′ or 5′-5′ TpT was reacted with a twofold molar excess of TPS in anhydrous DMF, at room temperature, for 5 min, followed by a 1 min in situ treatment of the reaction mixture with excess 7.0 N NH₄OH, at 0°C. The alkaline hydrolysis of 1, 8 and 9 proceeds without the assistance of 3′- and 5′-hydroxyl groups resulting in equimolar mixtures of thymidine (4) and thymidine 3′-phosphoramidate (6) (for the 3′-3′ isomer) or thymidine 5′-phosphoramidate (7) (for the 5′-5′ isomer) or 6 and 7 in equal quantities (for the 3′-5′ isomer).     

Synthesis of 3′-Amino-3′-deoxyguanosine 5′-Triphosphate

Abstract

Phosphorylation of 2′-0-acetyl-3′-trifluoroacetamido-3′-deoxy-N²-palmitoylguanosine with N-morpholino-O, O-bis(1-benzotriazolyl)phos-phate gives a 5′-phosphotriester. Removal of the benzotriazolyl group and addition of pyrophosphoric acid gave, after deblocking all protecting groups, GTP(3′NH₂).     

Pour en revenir à la masculinisation de statues-menhirs féminines du Rouergue

The literature regards the statues-menhirs from the Rouergue and the Haut-Languedoc as being predominantly male. When they have been the object of a gender change, the operation is always perceived as being a transformation from male effigies into female effigies. This interpretation postulates an initial male pre-eminence. However, in a previous article, this point of view seemed hardly constitute a general rule (Peeters, 2005). In the light of the statues-menhirs that have been discovered since, we have resumed the reading of the modified statues, as well as the quantitative approach of the groups and of the attributes, from the data updated and collated by M. Maillé (2010).     

利用~1H-NMR模拟谱研究三核苷酸A3′P(CH_3)5′A3′P(CH_3)5′A的构象性质

根据Altona等人的方法.利用~1H—NMR模拟谱分析了A3′P(CH_3)5A3′P(CH_3)5′A的三种非对映异构体:a、b和C的构象状态.发现:在室温下三个核糖环都是S型构象占优势(X_N≤0.44),而且随温度升高S型构象成分增多;两个二核苷酸片段-PAPA和APAP-的磷酸骨架扭角分别与A3′P(CH_3)5′A两种异构体a或b数值接近.差值约5°左右;二核苷酸片段中核糖环的重叠程度与手性磷原子的构型有关、R构型比S构型的核糖环重叠程度小;从而推测,A3′P(CH_3)5′A3′P(CH_3)5′A各种非对映异构体的稳定性为RR>RS.SR>SS,与化学合成中所见相符合.     

Synthesis and Structure Activity Relationships of 5-Substituted - 4′-thio-β-D-Arabinofuranosylcytosines

Abstract

Four 5-substituted (chloro, fluoro, bromo, methyl) 1-(4-thio-P-Darabinofuranosy1) cytosines and their a anomers were synthesized by a facile route in high yields. All of these nucleosides were evaluated for cytotoxicity against a panel of human tumor cell lines in vitro. Only 5-fluoro-1 -(4-thio-β-D-arabinofuranosyl)cytosine was found to be highly cytotoxic in all the cell lines and was further evaluated in vivo.     

Oligomerization of 3′-amino-3′-deoxyguanosine-5′-phosphorimidazolidate on a d(CpCpCpCpC) template

Summary 3-Amino-3-deoxyguanosine-5-phosphorimidazolidate (ImpGnh ₂) oligomerizes more rapidly and regiospecifically than related nucleotide derivatives on a d(CpCpCpCpC) template. The greater nucleophilicity of the amino group leads to efficient oligomerization even when the structure of the double-helical complex formed by the template and the substrate is not optimal for reaction. The use of amine-containing analogues should permit us to develop models of potentially prebiotic polymerization reactions that cannot be studied easily using natural nucleotides.     

Occurrence of Guanosine-5′-diphosphate-3′-diphosphate and Adenosine-5′-triphosphate-3′-diphosphate in Streptomyces galilaeus

Synthetic activity and existence of ppGpp and pppApp in an anthracycline-producing strain Streptomyces galilaeus were determined by radioimmunoassay and ³²P-labeling method during cultivation under both the antibiotic productive and non-productive conditions. The cellular ppGpp(pppGpp)-synthesizing activity was highest at the end of exponential growth, and 3-fold higher in the antibiotic-productive cultivation than in non-productive cultivation. The intracellular level of ppGpp determined by radioimmunoassay was high at the end of exponential growth, and afterwards its level decreased by one fifth. The low level of cellular ppGpp during the period of intense antibiotic production suggests that ppGpp consumption may play an important role in antibiotic production of S. galilaeus. The concentration of pppApp was not determined intracellularly by radioimmunoassay.     

Interaction of (2′ -5′) and (3′ -5′) Linked 2-Aminoadenylyl-3-aminoadenosines with Polyuridylic Acid

Abstract

2′-5′ and 3′-5′ linked 2-aminoadenylyl-2-aminoadenosines [(2′-5′)n²Apn²A (1) and (3′-5′)n²Apn²A (2)] were synthesized by condensation of 5′-O-monomethoxytrityl-N ² N ⁶-dibenzoyl-2-aminoadenosine and N ²,N ⁶,2′,3′-O-tetrabenzoyl-2-aminoadenosine 5′-phosphate using dicyclohexylcarbodiimide (DCC). The conformational properties of these dimers 1 and 2 were examined by UV, NMR and CD spectroscopy. The results reveal that the 2′-5′-isomer 1 takes a stacked conformation, which contains a larger base-base overlap and is more stable against thermal perturbation with respect to the 3′-5′-isomer 2. Interactions of 1 and 2 with polyuridylic acid (Poly (U)) were also examined by Tm, mixing curves, UV and CD spectra. Both the dinucleoside isomers 1 and 2 formed a complex of 1 : 2 stoichiometry with poly(U), which was much more stable than that of the corresponding ApA isomer     

Synthesis of Deoxyribonucleotidyl (3′-5′) Arabinonucleosides

Abstract

Two different synthetic routes using phosphotriester methodology have been utilized to prepare deoxyribonucleotidyl (3′–5′) arabinonucleosides containing 9-β-D-arabinofuranosyladenine (ara-A, vidarabine) and 1-β-D-arabinofuranosylcytosine (ara-C, cytarabine) at the 3′-terminus in amounts and purity (greater than 95%) suitable for NMR analysis.