A new family of sequence-specific DNA-cleaving agents directed by triple-helical structures: benzopyridoindole-EDTA conjugates

Sequence-specific DNA recognition can be achieved by oligonucleotides that bind to the major groove of oligopyrimidine x oligopurine sequences. These intermolecular structures could be used to modulate gene expression and to create new tools for molecular biology. Here we report the synthesis and biochemical characterization of triple helix-specific DNA cleaving reagents. It is based on the previously reported triplex-specific ligands, benzo[e]pyridoindole (BePI) and benzo[g]pyridoindole (BgPI), covalently attached to ethylenediaminotetraacetic acid (EDTA). In the presence of iron, a reducing agent and molecular oxygen, BgPI-EDTA x FeII but not BePI-EDTA x FeII induced a double-stranded cut in a plasmid DNA at the single site where a triplex-forming oligonucleotide binds. At single nucleotide resolution, it was found that upon triplex formation BePI-EDTA x FeII led to cleavage of the pyrimidine strand and protection of the purine strand. BgPI-EDTA x FeII cleaved both strands with similar efficiency. The difference in cleavage efficiency between the two conjugates was rationalized by the location of the EDTA x FeII moiety with respect to the grooves of DNA (major groove: BePI-EDTA x FeII, minor groove: BgPI-EDTA x FeII). This work paves the way to the development of a new class of triple helix directed DNA cleaving reagents. Such molecules will be of interest for sequence-specific DNA cleavage and for investigating triple-helical structures, such as H-DNA, which could play an important role in the control of gene expression in vivo.     

Superacid cyclization of 13E,17E- and 13E,17Z-bicyclogeranylfarnesols and their acetates — An effective structurally selective stereospecific route to scalarane sesterterpenoids

Institute of Chemistry, Moldavian SSR Academy of Sciences, Kishinev. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 759–760, September–October, 1988.     

Synthesis of D-D4FC, a biologically active nucleoside via an unprecedented palladium mediated Ferrier rearrangement-type glycosidation with an aromatization prone xylo-furanoid glycal

D-D4FC (1) is an anti-HIV agent currently under phase II clinical trial (Pharmaset Inc). Its molecular architecture is suitable for a Ferrier rearrangement kind of operation on a furanoid glycal to fix the position of the double bond and the relative stereochemistry. Despite the fact that classical Ferrier rearrangement does not work on furanoid glycals, a palladium mediated modified protocol has been developed for the glycosidation of an aromatization prone xylo-furanoid glycal (5) for the synthesis of D-D4FC.     

Theoretical study of “deep” fragmentation of hemin ion with successive loss of methyl and vinyl groups

The electronic and geometric structures, energy stability, normal mode frequencies, and spin density distribution have been calculated by the density functional theory B3LYP method with the Gen = 6-31+G*(Fe) + 6-31G(C,H,N,O), 6-31G*, and 6-311++G** basis sets for the deep fragmentation products of the free hemin ion with successive removal of methyl and vinyl groups in the electronic states with different multiplicities. The computation results are compared with the available experimental data and previous computation results for the fragmentation products of the isolated heme molecule and hemin ion with removal of carboxymethyl groups. The trends in the behavior of these properties are analyzed as a function of multiplicity, external charge, and the number of peripheral substituents at the porphyrin core.     

Pheromones of coleoptera. Communication 6. Synthesis of R,Z-14-methyl-8-hexadecenal (cis-trogodermal)

Conclusions The simple synthesis of optically active R,Z-14-methyl-8-hexadecenal (cis-trogodermal), the principal components of the aggregation pheromone ofTrogoderma granarium, was accomplished. The synthesis was based on the use of R-1-bromo-4-methylhexane and Z-4-chloro-2-buten-1-ol as the sources of the chiral and olefin fragments.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 906–910, April, 1987.     

The light 1P-shell nuclei

The binding energies and other characteristics of the light 1P-shell nuclei (N, Z8) are calculated. We use the method denoted as modified oscillator shell model (MOSM), proposed by one of the authors (Nguyen tien Nguyen: Czech. J. Phys. B31 (1981) 16). We succeed in choosing the parameter set of the Skyrme-type force, which gives satisfactory and interesting results.On leave fromFaculty of Physics, Hanoi University, Vietnam.The authors would like to thank I. Wilhelm for the useful discussion.     

Electron spin resonance studies of the radiolysis of bi-π-cyclopentadienylalkyls of molybdenum and tungsten

Exposure of (C₅H₅)₂MO(CH₃)₂ and (C₅H₅)₂W(CH₃)₂, prepared from the corresponding dichlorides, to ²⁰Co γ-rays at 77 K gave H₂C.CML₃ carbene species characterised by their ESR spectra, together with a central feature possibly due to the parent cations. Dilute solutions in CD₃OD gave features assigned to the parent anions which were converted on bleaching with visible light into methyl radicals, and H₂C.ML₃ radicals. From the magnitude of the ¹H and ¹⁸³W hyperfine coupling constants, it is deduced that the SOMO for H₂C.WL₃ radicals is strongly localised on carbon.Dilute solutions in aqueous sulphuric acid also gave species with A(2H) = 20 G, identified as the carbene derivatives, H₂C.Ml₃. These were formed on annealing, as signals assigned to HSO₄ · radicals were lost.