86 research outputs found

    Quadruplex DNA: sequence, topology and structure.

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    G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes

    Implementing core outcomes in kidney disease: report of the Standardized Outcomes in Nephrology (SONG) implementation workshop

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    There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes

    One-Pot Tandem Amidation, Knoevenagel Condensation, and Palladium-Catalyzed Wacker Type Oxidation/C–O Coupling: Synthesis of Chromeno-Annulated Imidazopyridines

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    A direct one-pot synthesis of chromeno-annulated imidazo­[1,2-<i>a</i>]­pyridines is achieved by the reaction of 2-amino-1-(2-ethoxy-2-oxoethyl)­pyridinium salts with 2-bromoarylaldehydes using Pd­(TFA)<sub>2</sub> as a catalyst and Cu­(OAc)<sub>2</sub> as an oxidant. The overall strategy involves tandem base-mediated amidation and Knoevenagel condensation, followed by palladium-catalyzed Wacker type oxidation and intramolecular C–O coupling reaction. The method is simple, tolerates different functional groups, and gives moderate to good yields of chromeno­[2′,3′:4,5]­imidazo­[1,2-<i>a</i>]­pyridin-12-one derivatives. The developed tandem reaction was also successfully applied for the synthesis of pyrano-fused imidazo­[1,2-<i>a</i>]­pyridines by using 3-bromo-3-arylacrylaldehydes

    One-Pot Tandem Amidation, Knoevenagel Condensation, and Palladium-Catalyzed Wacker Type Oxidation/C–O Coupling: Synthesis of Chromeno-Annulated Imidazopyridines

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    A direct one-pot synthesis of chromeno-annulated imidazo­[1,2-<i>a</i>]­pyridines is achieved by the reaction of 2-amino-1-(2-ethoxy-2-oxoethyl)­pyridinium salts with 2-bromoarylaldehydes using Pd­(TFA)<sub>2</sub> as a catalyst and Cu­(OAc)<sub>2</sub> as an oxidant. The overall strategy involves tandem base-mediated amidation and Knoevenagel condensation, followed by palladium-catalyzed Wacker type oxidation and intramolecular C–O coupling reaction. The method is simple, tolerates different functional groups, and gives moderate to good yields of chromeno­[2′,3′:4,5]­imidazo­[1,2-<i>a</i>]­pyridin-12-one derivatives. The developed tandem reaction was also successfully applied for the synthesis of pyrano-fused imidazo­[1,2-<i>a</i>]­pyridines by using 3-bromo-3-arylacrylaldehydes

    Photophysical studies of pyrenyl cyanostyrenes: effect of trifluoromethyl substitution on gelation

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    α-Cyanostyrenes bearing a planar pyrene unit and electron withdrawing trifluoromethyl units were designed and synthesized. The conformational restriction due to the presence of the cyano group on the double bond favors aggregation induced emission in aqueous media. The styrylpyrenes aggregate to form microstructures influenced by π–π stacking, cyano and CF3 substituent interactions. Importantly confluence of the pyrene ring and simple trifluoromethyl (CF3) unit allows the formation of a stable organogel with bathochromic shifts in emission. The formation of aggregates and the gel was substantiated using 1H NMR spectroscopy and scanning electron microscopy. The stability of the gels was assessed using rheology investigations and rationalized by single crystal X-ray data.by Jagadish Kumar Katla, Abhijeet Ojha, Akshay J. M. Nair, Rangan Krishnan and Sriram Kanva

    Ru(II)-Catalyzed [4 + 2]-Annulation of 2‑Alkenyl/Arylimidazoles with <i>N-</i>Substituted Maleimides and 1,4-Naphthoquinones: Access to Imidazo-Fused Polyheterocycles

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    Synthesis of imidazo-fused polyheterocyclic molecular frameworks, viz. imidazo[1,2-a]pyrrolo[3,4-e]pyridines, imidazo[2,1-a]pyrrolo[3,4-c]isoquinolines, and benzo[g]imidazo[1,2-a]quinoline-6,11-diones, has been achieved by the ruthenium(II)-catalyzed [4 + 2] C–H/N–H annulation of 2-alkenyl/2-arylimidazoles with N-substituted maleimides and 1,4-naphthoquinones. The developed protocol is operationally simple, exhibits broad substrate scope with excellent functional group tolerance, and provides the desired products in moderate to good yields. The mechanistic studies suggest that the reaction involves the formation of a C–C bond through Ru-catalyzed C(sp2)–H bond activation followed by intramolecular cyclization

    Ru(II)-Catalyzed [4 + 2]-Annulation of 2‑Alkenyl/Arylimidazoles with <i>N-</i>Substituted Maleimides and 1,4-Naphthoquinones: Access to Imidazo-Fused Polyheterocycles

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    Synthesis of imidazo-fused polyheterocyclic molecular frameworks, viz. imidazo[1,2-a]pyrrolo[3,4-e]pyridines, imidazo[2,1-a]pyrrolo[3,4-c]isoquinolines, and benzo[g]imidazo[1,2-a]quinoline-6,11-diones, has been achieved by the ruthenium(II)-catalyzed [4 + 2] C–H/N–H annulation of 2-alkenyl/2-arylimidazoles with N-substituted maleimides and 1,4-naphthoquinones. The developed protocol is operationally simple, exhibits broad substrate scope with excellent functional group tolerance, and provides the desired products in moderate to good yields. The mechanistic studies suggest that the reaction involves the formation of a C–C bond through Ru-catalyzed C(sp2)–H bond activation followed by intramolecular cyclization

    Two disjoint paths in chordal graphs

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    SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman
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