Institution
Torrey Pines Institute for Molecular Studies
Nonprofit•San Diego, California, United States•
About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.
Topics: Antigen, T cell, Peptide, Solid-phase synthesis, Cytotoxic T cell
Papers published on a yearly basis
Papers
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TL;DR: Since vasorelaxation was blocked by L-NAME, while indomethacin did not inhibit the effect, endothelium-derived nitric oxide seems to be involved in triterpenic 2 and 3 mode of action.
38 citations
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TL;DR: It is shown that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice, which establishes BET inhibition as a promising antifungal therapeutic strategy and identifies BDF1 as an antIfungal drug target that can be selectively inhibited without antagonizing human BET function.
Abstract: Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function.
37 citations
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TL;DR: The preference of MMP-1 for type II collagen appears to be primarily based on the flexibility of the hydrolysis site of type III collagen compared with types I and II, and further characterization of exosite determinants that govern interactions of M MPs with collagenous substrates should aid the development of pharmacotherapeutics that target individual MMPs.
37 citations
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TL;DR: The studies suggest that ERPs are an electrophysiological assay suitable for the exploration of the effects of genetic manipulations on neurosensory processing in mice and parallel human studies, demonstrating that decrements in P300 amplitude can be associated with a genetic vulnerability to alcoholism/alcohol preference.
37 citations
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TL;DR: In this paper, an alcohol-directed, nickel-catalyzed three-component umpolung carboamination of unactivated alkenes with aryl/alkenylboronic esters and electrophilic aminating reagents is reported.
Abstract: An alcohol-directed, nickel-catalyzed three-component umpolung carboamination of unactivated alkenes with aryl/alkenylboronic esters and electrophilic aminating reagents is reported. This transformation is enabled by specifically tailored O-(2,6-dimethoxybenzoyl)hydroxylamine electrophiles that suppress competitive processes, including undesired β-hydride elimination and transesterification between the alcohol substrate and electrophile. The reaction delivers the desired 1,2-carboaminated products with generally high regio- and syn-diastereoselectivity and exhibits a broad scope of coupling partners and alkenes, including complex natural products. Various mechanistic experiments and analysis of the stereochemical outcome with a cyclic alkene substrate, as confirmed by X-ray crystallographic analysis, support alcohol-directed syn-insertion of an organonickel(I) species.
37 citations
Authors
Showing all 2327 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eric J. Topol | 193 | 1373 | 151025 |
John R. Yates | 177 | 1036 | 129029 |
George F. Koob | 171 | 935 | 112521 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Gerald M. Edelman | 147 | 545 | 69091 |
Floyd E. Bloom | 139 | 616 | 72641 |
Stuart A. Lipton | 134 | 488 | 71297 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Chi-Huey Wong | 129 | 1220 | 66349 |
Klaus Ley | 129 | 495 | 57964 |
Nicholas J. Schork | 125 | 587 | 62131 |
Michael Andreeff | 117 | 959 | 54734 |
Susan L. McElroy | 117 | 570 | 44992 |
Peter E. Wright | 115 | 444 | 55388 |