Structure and Mechanism of an Aspartimide‐Dependent Peptide Ligase in Human Legumain

Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumain’s dual protease–ligase activities are pH‐ and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on–off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three‐dimensional MHC epitopes. The aspartate–aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP‐scarce environments.     

Hydrogenations at Room Temperature and Atmospheric Pressure with Mesoionic Carbene‐Stabilized Borenium Catalysts

1,2,3‐Triazolylidene‐based mesoionic carbene boranes have been synthesized in a convenient one‐pot protocol from the corresponding 1,2,3‐triazolium salts, base, and borane. Borenium ions are obtained by hydride abstraction and serve as catalysts in mild hydrogenation reactions of imines and unsaturated N‐heterocycles at ambient pressure and temperature.     

Sunlight curable hybrid organic–inorganic methacrylic‐based coatings: analysis of the cure mechanism and functional properties

An experimental ultraviolet (UV) polymerizable hybrid organic–inorganic protective coating, mainly intended for the surface protection of porous calcareous stone substrates, has been recently proposed and patented. The hybrid product evidenced an extraordinary hydrophobicity character, able to guarantee a high protection of the stone against water actions, as well as a high traspirability. Furthermore, it is able to equal the performance of commercial available coatings, with the important adjunctive advantage to be free solvent. The application of this product involves the use of a “dual curing” treatment, necessary to harden the coating applied on the substrate, representing this latter a technological limit. The dual curing treatment consists of 6 hr of exposure to a UV‐lamp plus 1 hr at 140°C in oven. In order to avoid this procedure, not easy to realize in situ, two different modifications of the composition of the hybrid product are proposed in this paper. The first one allows the photopolymerization of the hybrid coating only by sunlight exposure. The second one, even though requiring a UV exposure to photo‐polymerize the coating, does not need the subsequent thermal treatment at 140°C. Several experimental characterizations were performed on the newly developed hybrid products, in order to select an optimal composition for the formulations. The selected innovative products were, finally, applied on a calcareous stone substrate, typical of Apulia Region (Pietra Leccese, PL). Both coatings exhibit excellent water‐repellent action and a slight variation of the natural stone color. Copyright © 2014 John Wiley & Sons, Ltd.     

Integrated One‐Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates

The synthesis of pharmaceutical compounds via short‐lived intermediates in a microreactor is attractive, because of the fast flow and high throughput. Additionally, intermediates can be utilized sequentially to efficiently build up a library in a short time. Here we present an integrated microfluidic synthesis of biologically active thioquinazolinone libraries. Generation of o‐lithiophenyl isothiocyanate and subsequent reaction with aryl isocyanate is optimized by controlling the residence time in the microreactor to 16 ms at room temperature. Various S‐benzylic thioquinazolinone derivatives are synthesized within 10 s in high yields (75–98 %) at room temperature. These three‐step reactions involve two organolithium intermediates, an isothiocyanate‐functionalized aryllithium intermediate, and a subsequent lithium thiolate intermediate. We also demonstrate the gram‐scale synthesis of a multifunctionalized thioquinazolinone in the microfluidic device with a high yield (91 %) and productivity (1.25 g in 5 min).