ABSTRACT
Sulfur/selenium-containing electron-rich arenes (ERAs) exist in a wide range of both approved and investigational drugs with diverse pharmacological activities. These unique chemical structures and bioactive properties, if combined with the emerging DNA-encoded chemical library (DEL) technique, would facilitate drug and chemical probe discovery. However, it remains challenging, as there is no general DNA-compatible synthetic methodology available for the formation of C-S and C-Se bonds in aqueous solution. Herein, an in-solution direct oxidative coupling procedure that could efficiently integrate sulfur/selenium into the ERA under mild conditions is presented. This method features simple DNA-conjugated electron-rich arenes with a broad substrate scope and a transition-metal free process. Furthermore, this synthetic methodology, examined by a scale-up reaction test and late-stage precise modification in a mock peptide-like DEL synthesis, will enable its utility for the synthesis of sulfur/selenium-containing DNA-encoded libraries and the discovery of bioactive agents.
ABSTRACT
Ammonium and manganese removal by tunnel-structured manganese oxide is still enigmatic. Herein, tunnel-structured akhtenskites with different structural cations (Na-MnO x , Mg-MnO x Ca-MnO x , Fe-MnO x ) were synthesized by the KMnO4 and Mn2+ reaction in the presence of different metal cations, and were used to remove ammonium and manganese from aqueous solution. The results of the batch adsorption experiments indicated that akhtenskites effectively removed NH4 + and Mn2+, and the removal process fitted the pseudo-second-order model. By measuring the concentration of nitrate and nitrite, discriminating the adsorbed and oxidized Mn2+, and testing the zeta potential of the oxides, it can be concluded that NH4 + was merely removed by electrostatic adsorption via [triple bond, length as m-dash]Mn-O-; Mn2+ could also be adsorbed by ion exchange with [triple bond, length as m-dash]Mn-OH, and the adsorbed Mn2+ could be partly oxidized. The structural properties of the akhtenskites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific area, and X-ray photoelectron spectroscopy (XPS). The experimental results showed that ions with higher valence can result in a higher percentage of Mn(iii) in akhtenskite. Mg2+ can result in a lower proportion of lattice oxygen in the oxide, and Fe3+ can increase the pH of the point of zero charge. Both of them were unfavored for the oxidation of Mn2+. Moreover, it was found that Ca-MnO x had optimal removal performance in the catalytic oxidation of Mn2+ owing to appropriate percentages of Olatt and Mn(iii) and lower zeta potential. This study provides new insights into the synthesis and application of manganese oxides.
ABSTRACT
Membrane proteins on the cell surface perform a myriad of biological functions; however, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function. DNA-encoded chemical libraries (DELs) have emerged as a powerful technology for ligand discovery, but they are mainly limited to purified proteins. Here we report a method that can specifically label membrane proteins with a DNA tag, and thereby enable target-specific DEL selections against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation. We demonstrate the generality and performance of this method by screening a 30.42-million-compound DEL against the folate receptor, carbonic anhydrase 12 and the epidermal growth factor receptor on live cells, and identify and validate a series of novel ligands for these targets. Given the high therapeutic significance of membrane proteins and their intractability to traditional high-throughput screening approaches, this method has the potential to facilitate membrane-protein-based drug discovery by harnessing the power of DEL.
