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31.
Bergonzo C Campbell AJ de los Santos C Grollman AP Simmerling C 《Journal of the American Chemical Society》2011,133(37):14504-14506
Base eversion is a fundamental process in the biochemistry of nucleic acids, allowing proteins engaged in DNA repair and epigenetic modifications to access target bases in DNA. Crystal structures reveal end points of these processes, but not the pathways involved in the dynamic process of base recognition. To elucidate the pathway taken by 8-oxoguanine during base excision repair by Fpg, we calculated free energy surfaces during eversion of the damaged base through the major and minor grooves. The minor groove pathway and free energy barrier (6-7 kcal/mol) are consistent with previously reported results (Qi, Y.; Spong, M. C.; Nam, K.; Banerjee, A.; Jiralerspong, S.; Karplus, M.; Verdine, G. L. Nature 2009, 462, 762.) However, eversion of 8-oxoG through the major groove encounters a significantly lower barrier (3-4 kcal/mol) more consistent with experimentally determined rates of enzymatic sliding during lesion search (Blainey, P. C.; van Oijent, A. M.; Banerjee, A.; Verdine, G. L.; Xie, X. S. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 5752.). Major groove eversion has been suggested for other glycosylases, suggesting that in addition to function, dynamics of base eversion may also be conserved. 相似文献
32.
E. Rothenbach R. Laster P. Kolbach R. Buse O. Heinisch D. Satava W. Piratzky H. Krwawnik A. Heiduschka Elisabeth Bischoff W. Windisch M. Hamburg G. Bode H. Fink E. Berwald V. I. Staněk P. Pavlas Â. Boas A. Herzfeld F. M. Wieninger E. Helm 《Analytical and bioanalytical chemistry》1935,101(11-12):443-448
33.
Kadarkarai Murugan Jagannathan Madhavan Christina Mary Samidoss Chellasamy Panneerselvam Al Thabiani Aziz Arumugam Malathi Aruliah Rajasekar Amuthavalli Pandiyan Suresh Kumar Abdullah A. Alarfaj Akon Higuchi Giovanni Benelli 《Journal of Cluster Science》2018,29(2):337-344
Anopheles stephensi is a mosquito vector of malaria, which is still considered a relevant public health problem due to increasing outdoor transmission, growing resistance to insecticides used to target vectors, and antiplasmodial drugs as well. Thus, there is a vital need to explore novel sources of effective compounds. In this study, the hydrothermal method was used for the synthesis of bismuth oxyiodide (BiOI) nanoflakes. Furthermore, the toxicity of BiOI nanoflakes was evaluated for the first time on A. stephensi, as well as in vivo against the malaria parasite Plasmodium berghei. The synthesis of BiOI nanoflakes was confirmed by various characterization techniques, including X-ray diffraction, Fourier transform-infrared spectroscopy, field emission scanning electron microscopy and transmission electron microscopy (HR-TEM). LC50 of BiOI nanoflakes on A. stephensi were 2.263 ppm (larva I), 3.414 ppm (II), 4.956 ppm (III), 6.983 ppm (IV) and 8.605 ppm (pupae). In vivo antiplasmodial experiments conducted on P. berghei infecting albino mice showed 27.2% of chemosuppression after 4 days of treatment with 300 mg/kg/day of BiOI, a lower performance if compared to chloroquine. Overall, our results suggested that hydrothermal synthesis of BiOI nanoflakes may be considered to develop newer and safer tools for malaria vector control. 相似文献
34.
Viktor Reshetnikov Steffen Daum Dr. Christina Janko Weronika Karawacka Dr. Rainer Tietze Prof. Dr. Christoph Alexiou Dr. Solomiya Paryzhak Dr. Tetiana Dumych Prof. Dr. Rostyslav Bilyy Dr. Philipp Tripal Dr. Benjamin Schmid Dr. Ralf Palmisano Prof. Dr. Andriy Mokhir 《Angewandte Chemie (International ed. in English)》2018,57(37):11943-11946
Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate. 相似文献
35.
Christina Heroven Victoria Georgi Gaurav K. Ganotra Prof. Paul Brennan Finn Wolfreys Prof. Dr. Rebecca C. Wade Amaury E. Fernández‐Montalván Apirat Chaikuad Prof. Dr. Stefan Knapp 《Angewandte Chemie (International ed. in English)》2018,57(24):7220-7224
Prolonged drug residence times may result in longer‐lasting drug efficacy, improved pharmacodynamic properties, and “kinetic selectivity” over off‐targets with high drug dissociation rates. However, few strategies have been elaborated to rationally modulate drug residence time and thereby to integrate this key property into the drug development process. Herein, we show that the interaction between a halogen moiety on an inhibitor and an aromatic residue in the target protein can significantly increase inhibitor residence time. By using the interaction of the serine/threonine kinase haspin with 5‐iodotubercidin (5‐iTU) derivatives as a model for an archetypal active‐state (type I) kinase–inhibitor binding mode, we demonstrate that inhibitor residence times markedly increase with the size and polarizability of the halogen atom. The halogen–aromatic π interactions in the haspin–inhibitor complexes were characterized by means of kinetic, thermodynamic, and structural measurements along with binding‐energy calculations. 相似文献
36.
Dr. Kara M. Harmatys Dr. Juan Chen Danielle M. Charron Dr. Christina M. MacLaughlin Prof. Dr. Gang Zheng 《Angewandte Chemie (International ed. in English)》2018,57(27):8125-8129
Current biomimetics for medical applications use a single biomimetic approach to imitate natural structures, which can be insufficient for reconstructing structurally complex natural systems. Multipronged efforts may resolve these complexities. To achieve interesting nanostructure‐driven optical properties, a dual‐biomimetic system contained within a single nanoagent was engineered to recapitulate chlorosomes, efficient light‐harvesting organelles that have unique dye assemblies and tunable photonic properties. A series of chlorin dyes was synthesized, and these hydrophobic assemblies were stabilized inside a high‐density lipoprotein, a second biomimetic that enabled in vivo utility. This system resulted in tunable tumor imaging of intact (photoacoustic) and disrupted (activatable fluorescence) nanostructures. The successful demonstration of this multipronged biomimetic approach opens the door for reconstruction of complex natural systems for biomedical applications. 相似文献
37.
Loukou C Changenet-Barret P Rager MN Plaza P Martin MM Mallet JM 《Organic & biomolecular chemistry》2011,9(7):2209-2218
The design, synthesis and study of the photophysical and photochemical properties of the first biomimetic cyclodextrin (CD) model of photoactive yellow protein (PYP) are described. This model bears a deprotonated trans-p-coumaric acid chromophore, covalently linked via a cysteine moiety to a permethylated 6-monoamino β-CD. NMR and UV/Visible spectroscopy studies showed the formation of strong self-inclusion complexes in water at basic pH. Steady-state photolysis demonstrated that, unlike the free chromophore in solution, excitation of the model molecule leads to the formation of a photoproduct identified as the cis isomer by NMR spectroscopy. These observations provide evidence that the restricted CD cavity offers a promising framework for the design of biomimetic models of the PYP hydrophobic pocket. 相似文献
38.
Despotopoulou C Bauer RC Krasovskiy A Mayer P Stryker JM Knochel P 《Chemistry (Weinheim an der Bergstrasse, Germany)》2008,14(8):2499-2506
A single Br/Mg exchange of 1,2-dibromocyclopentene with iPrMgCl LiCl provides the corresponding beta-bromocyclopentenylmagnesium reagent, which can then be reacted with various electrophiles (yields: 65-82 %). In the presence of a secondary alkylmagnesium halide and Li2CuCl4 (2 mol %), these 2-bromoalkenylmagnesium compounds undergo bromine substitution and can then further react with electrophiles to give 1,2-difunctionalised cyclopentenes (63-79 %). The mechanism of this process is discussed. 相似文献
39.
40.
F. Kalkum M. Peter G. Barbastathis K. Buse 《Applied physics. B, Lasers and optics》2010,100(1):169-172
Using plasmonic resonances of metal films, enhanced transmission of light through sub-wavelength holes has been demonstrated. Here we show that external resonances can be employed as well: the transmission of 1.5-μm wavelength light through 600-nm holes is enhanced by a factor of 20 using a Fabry–Pérot arrangement. The maximal enhancement factor is determined by the limited reflectivity of metal surfaces. It seems promising to combine both effects—plasmonic resonances plus tailored photonic-crystal structures on top of the metal film—in order to realize efficient sub-wavelength light sources as they are required for, e.g., advanced spectroscopy and lithography. 相似文献