- TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
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Compounds of Formula (I) are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula (I) have the above structure, where the definitions of the variables are provided herein.
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Page/Page column 205
(2013/02/28)
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- Quantification of CH...π interactions: Implications on how substituent effects influence aromatic interactions
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Attractive interactions between a substituted benzene ring and an α-substituted acetate group were determined experimentally by using the triptycene model system. The attractive interaction correlates well with the Hammett constants σm (R2=0.90), but correlates much better with the acidity of the α-protons (R2=0.98). A predominant CH...π interaction was found to control the conformational preference of model compounds 1a-g. Despite the predominance of the CH...π interaction in compounds 1a-g, a Hammett plot displays a fairly straight line for the substituent effect. These results show that when using Hammett plots in a simplified model system, a system designed to study the effect of X...π interactions could capture the X-H...π interaction instead.
- Gung, Benjamin W.,Emenike, Bright U.,Lewis, Michael,Kirschbaum, Kristin
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supporting information; experimental part
p. 12357 - 12362
(2010/12/25)
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- Mass defect labeling of cysteine for improving peptide assignment in shotgun proteomic analyses
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A method for improving the identification of peptides in a shotgun proteome analysis using accurate mass measurement has been developed. The improvement is based upon the derivatization of cysteine residues with a novel reagent, 2,4-dibromo-(2′-iodo)acetanilide. The derivitization changes the mass defect of cysteine-containing proteolytic peptides in a manner that increases their identification specificity. Peptide masses were measured using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron mass spectrometry. Reactions with protein standards show that the derivatization of cysteine is rapid and quantitative, and the data suggest that the derivatized peptides are more easily ionized or detected than unlabeled cysteine-containing peptides. The reagent was tested on a 15N-metabolically labeled proteome from M. maripaludis. Proteins were identified by their accurate mass values and from their nitrogen stoichiometry. A total of 47% of the labeled peptides are identified versus 27% for the unlabeled peptides. This procedure permits the identification of proteins from the M. maripaludis proteome that are not usually observed by the standard protocol and shows that better protein coverage is obtained with this methodology.
- Hernandez, Hilda,Niehauser, Sarah,Boltz, Stacey A.,Gawandi, Vijay,Phillips, Robert S.,Amster, I. Jonathan
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p. 3417 - 3423
(2007/10/03)
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- LONG WAVELENGTH THIOL-REACTIVE FLUOROPHORES
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Reactive fluorescent dyes compositions and methods of using same are disclosed. Squaraine nucleus, Nile red nucleus, benzodioxazole nucleus, coumarin nucleus or aza coumarin nucleus dyes are disclosed dyes are disclosed having thiol-reactive groups. Squaraine nucleus, Nile Red nucleus, benzodioxazole nucleus, coumarin nucleus or aza coumarin nucleus dyes are disclosed that exhibit a fluorescence emission of at least about 575 nm. Biosensors are disclosed having a binding protein and a squaraine nucleus, Nile Red nucleus, benzodiaxazole nucleus, coumarin nucleus or aza coumarin nucleus.
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Page/Page column 14; 34-35
(2008/06/13)
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- Solid-phase synthesis of thioether-linked glycopeptide mimics for application to glycoprotein semisynthesis.
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[reaction: see text]. Glycoproteins are particularly suited to protein semisynthesis since homogeneous samples for biological analyses are not readily available using traditional recombinant techniques. Here we apply glycosyl iodoacetamides, normally used for the modification of bacterially derived proteins, to solid-phase glycopeptide synthesis. This provides access to glycopeptide alpha-thioesters, which may lend themselves to the semisynthesis of homogeneous N-linked glycoprotein mimics and novel glycopeptide libraries.
- Macmillan, Derek,Daines, Alison M,Bayrhuber, Monika,Flitsch, Sabine L
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p. 1467 - 1470
(2007/10/03)
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