A DNA molecule was designed and synthesized with three octanucleotide stretches linked by two hexakis(ethylene glycol) chains to form an intramolecular triplex in solution. The structural data obtained from a series of NMR NOESY spectra yielded interproton distances, and COSY experiments provided dihedral angle information for analysis of deoxyribose ring pucker. Using distance geometry followed by simulated annealing with restrained molecular dynamics and relaxation matrix refinement, a well-refined ensemble of conformations was calculated. Although some NOE cross-peaks involving protons of the hexakis(ethylene glycol) linker could be identified, most could not be assigned and the conformations of the linkers were not determined. The deoxyribose conformations are predominantly of the S type, except for the protonated cytosine residues in the third strand which show hybrid N and S character. Overall, the duplex part of the molecule resembles a B-DNA double helix with the third strand bound in its major groove by Hoogsteen hydrogen bonds. This structure provides a basis for comparison with triplexes containing noncanonical or nonnatural nucleotides.
Incorporation of the modified base 5-(1-propynl)-2'-deoxyuridine (propynylU) in the third strand of a triplex leads to enhanced triplex stabilization. To investigate effects of the propyne nucleotide on triplex structure and the factors underlying the increased stability, we have determined the solution structure of the intramolecular DNA pyrmidine-purine-pyrimdine d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-PCPCPCPP) (PDD-EG), which contains 5-(1-propynl)-2'-deoxyuridine (P) in the third strand and hexakis(ethylene glycol) linkers [(EG)6]. The structure was calculated using X-PLOR with distance and dihedral angle restraints obtained from two-dimensional NMR experiments and refined with the direct relaxation matrix method. The structures show that the extended aromatic electron cloud of the propynylU nucleotide stacks well over the 5'-neighboring nucleotides, resulting in increased stabilization. The propynylU nucleotides also affect the overall structure of the triple helix. A comparison of the structure to that of the nonmodified intramolecular DNA triplex of the same sequence, d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-TCTCTCTT) (DDD-EG), shows that PDD-EG has a more A-DNA like X displacement and inclination than DDD-EG yet still maintains predominantly S-type sugar puckers as found in DDD-EG and other DNA triplexes.
Objective: Mosquito-borne diseases pose a threat to individual health and population health on both a local and a global level. The threat is even more exaggerated during disasters, whether manmade or environmental. With the recent Zika virus outbreak, it is important to highlight other infections that can mimic the Zika virus and to better understand what can be done as public health officials and health care providers. Methods: This article reviews the recent literature on the Zika virus as well as chikungunya virus and dengue virus. Results: The present findings give a better understanding of the similarities and differences between the 3 infections in terms of their characteristics, clinical presentation, diagnosis methodology, and treatment and what can be done for prevention. Additionally, the article highlights a special population that has received much focus in the latest outbreak, the pregnant individual. Conclusion: Education and training are instrumental in controlling the outbreak, and early detection can be lifesaving. (Disaster Med Public Health Preparedness. 2017;11:290-299)
ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.
A novel triazene, 4-[(E)-2-(4-cyanophenyl)diazenyl]-morpholine (1) was prepared via a diazonium ion coupling reaction between 4-aminobenzonitrile and morpholine. The x-ray structure of 1 was determined and evidenced p delocalization in the triazene subunit. The room temperature absorption spectrum of 1 in acetonitrile was dominated by an intense triazene-centered p!p* transition at 325 nm. Compound 1 was observed to be luminescent, with an emission maximum at 434 nm in room temperature acetonitrile solution. The emission spectrum of 1 in propionitrile glass at 77K exhibited a narrowed emission band with a maximum at 449 nm. Broad emission from 400-700 nm with poorly resolved vibrational structure was observed from solid 1 at room temperature.
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