contributed equally to this work.Receptor endocytosis is regulated by ligand binding, and receptors may signal after endocytosis in signaling endosomes. We hypothesized that signaling endosomes containing different types of receptors may be distinct from one another and have different physical characteristics. To test this hypothesis, we developed a high-resolution organelle fractionation method based on mass and density, optimized to resolve endosomes from other organelles. Three different types of receptors undergoing ligand-induced endocytosis were localized predominately in endosomes that were resolved from one another using this method. Endosomes containing activated receptor tyrosine kinases (RTKs), TrkA and EGFR, were similar to one another. Endosomes containing p75 NTR (in the tumor necrosis receptor superfamily) and PAC1 (a G-protein-coupled receptor) were distinct from each other and from RTK endosomes. Receptorspecific endosomes may direct the intracellular location and duration of signal transduction pathways to dictate response to signals and determine cell fate.
1,3-Oxazinen-4-ones are medicinally important scaffolds which have traditionally been accessed using a hetero-Diels-Alder approach or more recently using a cobalt-catalyzed three-component cycloaddition. Herein we report a novel strategy to access this scaffold which allows for the rapid and high yielding synthesis of 1,3-oxazinen-4-ones under ambient temperature and pressures with improved substrate scope.
Expedient Metal-Free Synthesis of 1,3-Oxazinen-4-ones. -Starting from 1-benzoyl or 1-acetylcyclopropane-1-carboxylic acid and a range of imines, the title compounds are synthesized in a high-yielding operationally simple and rapid manner. -(CRAIG, A. J.; VAN DER SALM, L.; STEVENS-CULLINANE, L.; LUCAS, N. T.; TAN, E. W.; HAWKINS*, B. C.; Org. Lett. 17 (2015) 2, 234-237, http://dx.
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