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Molecular Scaffold (molecular + scaffold)
Selected AbstractsAn Efficient Asymmetric Synthesis of 2-Substituted 1,4-Benzodiazepin-3-one as a Potential Molecular ScaffoldEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2005Nuria Cabedo Abstract 2-Substituted 1,4-benzodiazepine-2-one compounds (9,12) were obtained by a highly diastereoselective alkylation of a seven-membered ring benzolactam (8) in the presence of (R)-phenylglycinol as a chiral inductor. The corresponding acid derivative (16) afforded a conformationally constrained structure suitable for preparing peptidomimetic analogues useful as a novel molecular scaffold. After cleavage of the chiral appendage this approach might also lead efficiently to enantiomerically pure 2-substituted benzodiazepines (15). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Diversity-Oriented Synthesis of Morpholine-Containing Molecular ScaffoldsCHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2009Claudia Lalli Dr. Couple and cyclize: A coupling,cyclization strategy employing building blocks from the chiral pool was applied for the generation of morpholine-containing scaffolds (see scheme). The modulation of both the reaction conditions and the stereochemistry of the building blocks allowed the first degree of skeletal diversity, followed by functional group pairing of strategic appendages of selected molecular scaffolds to achieve more complex molecular frameworks. [source] An Efficient Asymmetric Synthesis of 2-Substituted 1,4-Benzodiazepin-3-one as a Potential Molecular ScaffoldEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2005Nuria Cabedo Abstract 2-Substituted 1,4-benzodiazepine-2-one compounds (9,12) were obtained by a highly diastereoselective alkylation of a seven-membered ring benzolactam (8) in the presence of (R)-phenylglycinol as a chiral inductor. The corresponding acid derivative (16) afforded a conformationally constrained structure suitable for preparing peptidomimetic analogues useful as a novel molecular scaffold. After cleavage of the chiral appendage this approach might also lead efficiently to enantiomerically pure 2-substituted benzodiazepines (15). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membraneGLIA, Issue 6 2008Patrice E. Fort Abstract The dystrophin-associated proteins (DAPs) complex consisting of dystroglycan, syntrophin, dystrobrevin, and sarcoglycans in muscle cells is associated either with dystrophin or its homolog utrophin. In rat retina, a similar complex was found associated with dystrophin-Dp71 that serves as an anchor for the inwardly rectifying potassium channel Kir4.1 and the aqueous pore, aquaporin-4 (AQP4). Here, using immunofluorescence imaging of isolated retinal Müller glial cells and co-immunoprecipitation experiments performed on an enriched Müller glial cells end-feet fraction, we investigated the effect of Dp71 deletion on the composition, anchoring, and membrane localization of the DAPs,Kir4.1 and/or ,AQP4 complex. Two distinct complexes were identified in the end-feet fraction associated either with Dp71 or with utrophin. Upon Dp71 deletion, the corresponding DAPs complex was disrupted and a compensating utrophin upregulation was observed, accompanied by diffuse overall staining of Kir4.1 along the Müller glial cells and redistribution of the K+ conductance. Dp71 deficiency was also associated with a marked reduction of AQP4 and ,-dystroglycan expression. Furthermore, it was observed that the Dp71,DAPs dependent complex could be, at least partially, associated with a specific membrane fraction. These results demonstrate that Dp71 has a central role in the molecular scaffold responsible for anchoring AQP4 and Kir4.1 in Müller cell end-feet membranes. They also show that despite its close relationship to the dystrophin proteins and its correlated upregulation, utrophin is only partially compensating for the absence of Dp71 in Müller glial cells. © 2008 Wiley-Liss, Inc. [source] Enhancing molecular discovery using descriptor-free rearrangement clustering techniques for sparse data setsAICHE JOURNAL, Issue 2 2010Peter A. DiMaggio Jr. Abstract This article presents a descriptor-free method for estimating library compounds with desired properties from synthesizing and assaying minimal library space. The method works by identifying the optimal substituent ordering (i.e., the optimal encoding integer assignment to each functional group on every substituent site of molecular scaffold) based on a global pairwise difference metric intended to capture smoothness of the compound library. The reordering can be accomplished via a (i) mixed-integer linear programming (MILP) model, (ii) genetic algorithm based approach, or (iii) heuristic approach. We present performance comparisons between these techniques as well as an independent analysis of characteristics of the MILP model. Two sparsely sampled data matrices provided by Pfizer are analyzed to validate the proposed approach and we show that the rearrangement of these matrices leads to regular property landscapes which enable reliable property estimation/interpolation over the full library space. An iterative strategy for compound synthesis is also introduced that utilizes the results of the reordered data to direct the synthesis toward desirable compounds. We demonstrate in a simulated experiment using held out subsets of the data that the proposed iterative technique is effective in identifying compounds with desired physical properties. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Neurodevelopmental sequelae of postnatal maternal care in rodents: clinical and research implications of molecular insightsTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 3-4 2007Arie Kaffman Parental care plays an important role in the emotional and cognitive development of the offspring. Children who have been exposed to abuse or neglect are more likely to develop numerous psychopathologies, while good parent,infant bonding is associated with improved resiliency to stress. Similar observations have also been reported in non-human primates and rodents, suggesting that at least some neurodevelopmental aspects of parent,offspring interactions are conserved among mammals and could therefore be studied in animals. We present data to suggest that frequency of licking and grooming provided by the dam during a critical period in development plays an important role in modifying neurodevelopment. These findings are examined in the broader context in which exposure to other sensory modalities such as vision or hearing during a specific period in development shapes brain development with functional consequences that persist into adulthood. We also discuss recent rodent work showing that increased frequency of licking and grooming provided by the dam during the first week of life is associated with changes in DNA methylation of promoter elements that control expression of these genes and behavior. The stability of DNA methylation in postmitotic cells provides a possible molecular scaffold by which changes in gene expression and behavioral traits induced by postnatal maternal care are maintained throughout life. Finally, the relevance of findings reported in rodents to those noted in non-human primates and humans are assessed and the research and clinical implications of these observations for future work are explored. [source] Solution structure of the cyclic peptide contryphan-Vn, a Ca2+ -dependent K+ channel modulatorBIOPOLYMERS, Issue 3 2004Tommaso Eliseo Abstract The solution structure of contryphan-Vn, a cyclic peptide with a double cysteine S,S bridge and containing a D -tryptophan extracted from the venom of the cone snail Conus ventricosus, has been determined by NMR spectroscopy using a variety of homonuclear and heteronuclear NMR methods and restrained molecular dynamics simulations. The main conformational features of backbone contryphan-Vn are a type IV ,-turn from Gly 1 to Lys 6 and a type I ,-turn from Lys 6 to Cys 9. As already found in other contryphans, one of the two prolines,the Pro4,is mainly in the cis conformation while Pro7 is trans. A small hydrophobic region probably partly shielded from solvent constituted from the close proximity of side chains of Pro7 and Trp8 was observed together with a persistent salt bridge between Asp2 and Lys6, which has been revealed by the diagnostic observation of specific nuclear Overhauser effects. The salt bridge was used as a restraint in the molecular dynamics in vacuum but without inserting explicit electrostatic contribution in the calculations. The backbone of the unique conformational family found of contryphan-Vn superimposes well with those of contryphan-Sm and contryphan-R. This result indicates that the contryphan structural motif represents a robust and conserved molecular scaffold whose main structural determinants are the size of the intercysteine loop and the presence and location in the sequence of the D -Trp and the two Pro residues. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004 [source] Asymmetric Counterion Pair Catalysis: An Enantioselective Brønsted Acid-Catalyzed ProtonationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2008Magnus Rueping Abstract A new asymmetric Brønsted acid-catalyzed cascade reaction involving a 1,4-addition, enantioselective protonation and 1,2-addition has been developed. This organocatalytic cascade not only provides for the first time 3- and 2,3-substituted tetrahydroquinolines and octahydroacridines in good yields with high dia- and enantioselectivities under mild reaction conditions but additionally represents the first example of a chiral Brønsted acid-catalyzed protonation reaction in an organocatalytic domino reaction. Furthermore, the new Brønsted acid-catalyzed hydride-proton-hydride transfer cascade can be applied to prepare new molecular scaffolds with up to three new stereocenters in an efficient one-pot reaction sequence. [source] Diversity-Oriented Synthesis of Morpholine-Containing Molecular ScaffoldsCHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2009Claudia Lalli Dr. Couple and cyclize: A coupling,cyclization strategy employing building blocks from the chiral pool was applied for the generation of morpholine-containing scaffolds (see scheme). The modulation of both the reaction conditions and the stereochemistry of the building blocks allowed the first degree of skeletal diversity, followed by functional group pairing of strategic appendages of selected molecular scaffolds to achieve more complex molecular frameworks. [source] | ||||||||||