Studies on the ability of minor groove binders to induce supercoiling in DNA

AbstractThe effect of various non-intercalating minor groove binders on closed circular DNA in the presence of topoisomerase I has been studied by means of agarose gel electrophoresis. Analogues of the netropsin series (lexitropsins) and SN-6999 can effectively produce positive supercoils, as indicated by analysis of the topoisomers in the presence of chloroquine and the evaluated linking number changes. Analogues of the distamycin series are less effective, and bisquaternary ammonium heterocycles, as well as DAPI and pentamidine, were found to be ineffective ligands. The large differences observed in the ability of minor groove binders to induce positive supercoils are discussed

Complex patterns of spontaneous initiations and terminations of reentrant circulation in a loop of cardiac tissue

A two-component model is developed that consists of a discrete loop of cardiac cells that circulates action potentials together with a cardiac pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and their interactions with the pacer are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability of reentrant circulation (T-bistability) and in some cases, also phase-resetting interactions with the pacer.Comment: 27 pages, 10 figures, 61 references; A version of this paper (same results) is to appear in the Journal of Theoretical Biology; arXiv V2 adds helpful commments to facilitate reading and corrects minor errors in presentatio

Synthesis complete 1H assignments and conformations of the self-complementary hexadeoxyribonucleotide [d(CpGpApTpCpG)]2 and its fragments by high field NMR

International audienceSynthesis, complete 1H assignments and conformations of the self-complementary hexadeoxyribonucleotide [d(CpGpApTpCpG)]2 and its fragments by high field NMR ABSTRACT The two deoxyribonucleotides [d(CpGpApTpCpG)] and [d(CpGpCpG)] were synthesized by the phosphotriester method. Their guplex form under {he conditions of the 1H-nmr experiments was proven by end 32p labeling with T4 polynucleotide kinase followed by butt end joining employing the absolute specificity of T4 ligase for double stranded DNA and analysis using gel electro-phoresis and autoradiography. Complete nmr assignment of the YH chemical shifts and coupling constants was achieved. The assignments were secured using sequential decoupling, NOE difference measurements, and two-dimensional COSY and SECSY experiments. Spectrum simulation confirmed the experimental values of chemical shifts and joupling constants. The techniques for the assignment outlined together with Jlp and 2-D heteronuclear shift correlation permit an approach to a systematic analysis of more complex single-strand and duplex ol i godeoxyri bonucl eotides