36 research outputs found
Catalyst-Switchable Regiocontrol in the Direct Arylation of Remote CâH Groups in Pyrazolo[1,5-<i>a</i>]pyrimidines
The regiodivergent palladium-catalyzed CâH arylation of pyrazolo[1,5-a]pyrimidine has been achieved, wherein the switch in regioselectivity between positions C3 and C7 is under complete catalyst control. A phosphine-containing palladium catalyst promotes the direct arylation at the most acidic position (C7), whereas a phosphine-free catalyst targets the most electron-rich position (C3)
NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants
Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge
Palladium-Catalyzed <i>Ortho</i>-Arylation of Carbamate-Protected Estrogens
The palladium-catalyzed <i>ortho</i>-arylation of diethyl
carbamate-protected estrone and estriol with aryl iodides gives the
2-arylated analogues. Subsequent removal of the carbamate directing
group furnishes 2-arylated estrone, estradiol, or estriol depending
on the method used
Microsecond Molecular Dynamics Simulations of Influenza Neuraminidase Suggest a Mechanism for the Increased Virulence of Stalk-Deletion Mutants
Deletions in the
stalk of the influenza neuraminidase (NA) surface
protein are associated with increased virulence, but the mechanisms
responsible for this enhanced virulence are unclear. Here we use microsecond
molecular dynamics simulations to explore the effect of stalk deletion
on enzymatic activity, contrasting NA proteins from the A/swine/Shandong/N1/2009
strain both with and without a stalk deletion. By modeling and simulating
neuraminidase apo glycoproteins embedded in complex-mixture lipid
bilayers, we show that the geometry and dynamics of the neuraminidase
enzymatic pocket may differ depending on stalk length, with possible
repercussions on the binding of the endogenous sialylated-oligosaccharide
receptors. We also use these simulations to predict previously unrecognized
druggable âhotspotsâ on the neuraminidase surface that
may prove useful for future efforts aimed at structure-based drug
design