Seeing the Unseen: The Role of Liquid Crystals in Gas-Sensing Technologies.

Fast, real-time detection of gases and volatile organic compounds (VOCs) is an emerging research field relevant to most aspects of modern society, from households to health facilities, industrial units, and military environments. Sensor features such as high sensitivity, selectivity, fast response, and low energy consumption are essential. Liquid crystal (LC)-based sensors fulfill these requirements due to their chemical diversity, inherent self-assembly potential, and reversible molecular order, resulting in tunable stimuliresponsive soft materials. Sensing platforms utilizing thermotropic uniaxial systems-nematic and smectic-that exploit not only interfacial phenomena, but also changes in the LC bulk, are demonstrated. Special focus is given to the different interaction mechanisms and tuned selectivity toward gas and VOC analytes. Furthermore, the different experimental methods used to transduce the presence of chemical analytes into macroscopic signals are discussed and detailed examples are provided. Future perspectives and trends in the field, in particular the opportunities for LC-based advanced materials in artificial olfaction, are also discussed.

ADP-ribosylated proteins as old and new drug targets for anticancer therapy: the example of ARF6.

Post-translational modifications of cellular proteins by mono- or poly-ADP-ribosylation are associated with numerous cellular processes. ADP-ribosylation reactions are important in the nucleus, and in mitochondrial activity, stress response signaling, intracellular trafficking, and cell senescence and apoptosis decisions. These reversible reactions add ADP-ribose to target proteins via specific enzymes to form the ADP-ribosylated protein; the cleaveage of this covalent bond is performed via hydrolases. Deficiencies in these enzymatic activities lead to cell death or tumor formation, thus defining their functional roles and impact on human disease. Unlike mono- ADP-ribosyltransferases, poly-ADP-ribose polymerases (PARPs) have been at the frontline of drug discovery since the 1980s. PARP1 is a valuable therapeutic target, with a central role in responses to DNA damage. With mono-ADP-ribosylation now linked to human diseases, such as inflammation, diabetes, neurodegeneration and cancer metastasis, novel and equally important functions of mono-ADPribosylation in cell signaling pathways can now be defined. Recently, we reported mono-ADP-ribosylation of ADP-ribosylation factor 6 (ARF6), a small G-protein of the Ras superfamily. In addition to its involvement in actin remodeling, plasma membrane reorganization and vesicular transport, ARF6 contributes to cancer progression through activation of cell motility and invasion. Consequently, targeting this modification will counteract the pro-invasive effects of ARF6, providing innovative anti-tumor therapy. This review summarizes our present knowledge of the enzymes and targets involved in ADP-ribosylation reactions, and describes in silico approaches to visualize their site of interaction and to identify the precise site for ADP-ribosylation. This should ultimately improve pharmacological strategies to enhance both anti-tumor efficacy and treatment of a number of inflammatory and neurodegenerative disorders.

Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives.

Research on cancer epigenetics has flourished in the last decade. Nevertheless growing evidence point on the importance to understand the mechanisms by which epigenetic changes regulate the genesis and progression of cancer growth. Several epigenetic targets have been discovered and are currently under validation for new anticancer therapies. Drug discovery approaches aiming to target these epigenetic enzymes with small-molecules inhibitors have produced the first pre-clinical and clinical outcomes and many other compounds are now entering the pipeline as new candidate epidrugs. The most studied targets can be ascribed to histone deacetylases and DNA methyltransferases, although several other classes of enzymes are able to operate post-translational modifications to histone tails are also likely to represent new frontiers for therapeutic interventions. By acknowledging that the field of cancer epigenetics is evolving with an impressive rate of new findings, with this review we aim to provide a current overview of pre-clinical applications of smallmolecules for cancer pathologies, combining them with the current knowledge of epigenetic targets in terms of available structural data and drug design perspectives.

CoCoCo: a free suite of multiconformational chemical databases for high-throughput virtual screening purposes.

In the last few decades, virtual screening has proved to be able to guide the selection of new hit compounds with predefined biological activity. However, the usage of these computational techniques is often associated with resource- and time-consuming preparation protocols. In this work we present Commercial Compound Collection (CoCoCo), a suite of free and ready-to-use chemical databases to help setting up in silico screening projects. CoCoCo collects molecular structural information of commercial compounds from various chemical vendors by merging them in a unique, non-redundant format. CoCoCo databases are prepared with transparent and straightforward routines based on state-of-the-art computational tools that introduce comprehensive structural information about tautomers, stereoisomers and conformational states of each compound. CoCoCo suite is especially conceived as a set of valuable tools that may help a wide range of researchers who wish to initiate their own project in the field of computational drug design. CoCoCo suite is available free of charge at the website .