Zigang Li

Gold-Catalyzed Organic Transformations

Thanks to its unusual stability, metallic gold has been used for thousands of years in jewelry, currency, chinaware, and so forth. However, gold had not become the chemists’ “precious metal” until very recently. In the past few years, reports on gold-catalyzed organic transformations have increased substantially. Thanks to gold-based catalysts, various organic transformations have been accessible under facile conditions with both high yields and chemoselectivity.

The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism.

MexR is a MarR family protein that negatively regulates multidrug efflux systems in the human pathogen Pseudomonas aeruginosa. The mechanism of MexR-regulated antibiotic resistance has never been elucidated in the past. We present here that two Cys residues in MexR are redox-active. They form intermonomer disulfide bonds in MexR dimer with a redox potential of −155 mV. This MexR oxidation leads to its dissociation from promoter DNA, derepression of the mexAB–oprM drug efflux operon, and increased antibiotic resistance of P. aeruginosa. We show computationally that the formation of disulfide bonds is consistent with a conformation change that prevents the oxidized MexR from binding to DNA. Collectively, the results reveal that MexR is a redox regulator that senses peroxide stress to mediate antibiotic resistance in P. aeruginosa.

Platinum(II)-catalyzed intramolecular cyclization of o-substituted aryl alkynes through sp3 C-H activation.

Ring leader: PtCl(2) catalyzes intramolecular cyclization of o-isopropyl or o-benzyl aryl alkynes to give substituted indene derivatives with good yields and high selectivity. This reaction appears to proceed through an sp(3) C-H activation and 1,4-hydrogen migration pathway (see scheme).

Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2.

MicroRNAs (miRNAs) control gene expression by promoting degradation or repressing translation of target mRNAs. The components of the miRNA pathway are subject to diverse modifications that can modulate the abundance and function of miRNAs. Iron is essential for fundamental metabolic processes, and its homeostasis is tightly regulated. Here we identified iron chelators as a class of activator of the miRNA pathway that could promote the processing of miRNA precursors. We show that cytosolic iron could regulate the activity of the miRNA pathway through poly(C)-binding protein 2 (PCBP2). PCBP2 is associated with Dicer and promotes the processing of miRNA precursors. Cytosolic iron could modulate the association between PCBP2 and Dicer, as well as the multimerization of PCBP2 and its ability to bind to miRNA precursors, which can alter the processing of miRNA precursors. Our findings reveal a role of iron homeostasis in the regulation of miRNA biogenesis.