Showing papers in "Chemistry & Biology in 2016"

TL;DR: How combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data is discussed.

TL;DR: This Review highlights recent developments in the understanding of the biosynthesis of several bacterial RiPP family members, the use of the RiPP biosynthetic machinery for generating novel macrocyclic peptides, and the implementation of tools designed to guide the discovery and characterization of novel RiPPs.

TL;DR: This review highlights advances and successes in approaches to targeting RNA with diverse small molecules, and the potential for these technologies to pave the way to new types of RNA-targeted therapeutics.

TL;DR: This review covers several nucleic acid modifications that play important regulatory roles in biological systems, especially in regulation of gene expression: 5-methylcytosine and its oxidative derivatives, and N(6)-methyladenine (6mA) in DNA; N( 6)-methyladenosine (m(6)A), pseudouridine (Ψ), and 5- methylcytidine (m (5)C) in mRNA and long non-coding RNA.

TL;DR: In this article, the authors analyzed the compound sensitivity data of 6,259 lethal compounds from the NCI-60 project and identified 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their median growth inhibitory GI50 profiles across the 60 cell lines.

TL;DR: The progress in probe development described here suggests that optical imaging is an important and rapidly developing field of study that encourages continued collaboration among chemists, biologists, and clinicians to further refine these tools for interventional surgical imaging, as well as for diagnostic and therapeutic applications.

TL;DR: It is proposed that symmetrical triplex-forming motifs, especially those in cis-acting lncRNAs, favor triplex formation, and the effects of lncRNA structures, protein or ligand binding, and chromatin structures on the lnc RNAs triPlex formation are considered.

TL;DR: This work introduces a new data-driven approach (PrOCTOR) that directly predicts the likelihood of toxicity in clinical trials and integrates the properties of a compound's targets and its structure to provide a new measure, the PrOCTor score.

TL;DR: Advances in the discovery of small-molecule agr modulators are highlighted and how the newly available biochemical and structural information might be leveraged for the design of next-generation therapeutics targeting the agr system are highlighted.

TL;DR: A series of multifunctional molecules that contained Tau-recognition moieties and E3 ligase-binding moieties to enhance Tau degradation were designed and synthesized and TH006 had the highest activity of inducing Tau degradation by increasing its poly-ubiquitination.

TL;DR: This evolution of DNA CT chemistry is described, from the discovery of fundamental chemical principles to applications in diagnostic strategies and possible roles in biology.

TL;DR: A reactivity-based chemoproteomic platform is used to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy.

TL;DR: A molecular understanding of gut microbial activities will be critical for elucidating and manipulating these organisms' contributions to human health and disease.

TL;DR: Fasnall, a thiophenopyrimidine selectively targeting FASN through its co-factor binding sites, showed potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer, particularly when combined with carboplatin.

TL;DR: These findings provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus and may represent a new therapeutic strategy against Ebola virus disease.

TL;DR: This study identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response and provides a new strategy for prolonging antibiotic shelf life.

TL;DR: It is shown that chronic oxidative stress yields an EGFR subpopulation that is refractory to the FDA-approved drug afatinib, and the significance of redox biology to understanding kinase regulation and drug pharmacology is highlighted.

TL;DR: It is shown that proliferating fibroblasts prefer to take up palmitate from the extracellular environment over synthesizing it de novo, suggesting that cells scavenging exogenous lipids may be less susceptible to drugs targeting glycolysis and deNovo lipid synthesis.

TL;DR: A novel single-chain variable fragment antibody, D1, with high binding selectivity for parallel G-quadruplexes in vitro and in vivo is reported, finding it to be a valuable tool for determination of G- quadruplex and its conformation.

TL;DR: Recent advances in phenotypic readouts and MoA determination are highlighted by discussing several case studies in which both activities were required for understanding the chemical biology involved and, in some cases, advancing toward clinical development.

TL;DR: It is confirmed that in vitro activity and selectivity translate well into the cellular environment and suggest that the inhibitors presented are powerful tools to elucidate JAK3-specific functions.

TL;DR: This mini-review summarizes the currently available methodologies to detect and prove direct target engagement in cells and offers a critical view of their key advantages and disadvantages.

TL;DR: It is demonstrated that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14 and OTUD2 and OT UD3 show remarkable linkage-specific reactivity with the development of active site-directed probes and fluorogenic substrates that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety.

TL;DR: The discovery is reported that kongensin A (KA), a natural product isolated from Croton kongensis, is a potent inhibitor of necroptosis and an inducer of apoptosis and a new bioorthogonal ligation method (TQ ligation) is revealed that reveals that the direct cellular target of KA is heat shock protein 90 (HSP90).

TL;DR: The results suggest that multiple structurally unrelated natural products have evolved to target overlapping but non-identical binding sites on Sec61, thereby producing distinct biological outcomes.

TL;DR: High-resolution crystal structures of an ancestral arginine-binding protein in complex with l-arginine and l-glutamine show that the promiscuous binding of l-Glutamine is enabled by multi-scale conformational plasticity, water-mediated interactions, and selection of an alternative conformational substate productive for l- glutamine binding.

TL;DR: Compared the in vitro activation profiles of related monospecific and multispecific modules that either strictly incorporate leucine or arginine or incorporate chemically diverse amino acids in parallel into microcystin to inspire novel synthetic biology approaches and demonstrate how recombination platforms of NRPSs have developed in nature.

TL;DR: H6PD silencing can cause apoptosis and further sensitize cells to PARPi, suggesting that H6PD may be, in addition to its established role in metabolic disorders, a new anticancer target.

TL;DR: Environmental signals can drastically alter the efficacy of small-molecule QS inhibitors in P. aeruginosa and possibly other pathogens, and can be extrapolated to predict QS inhibitor activity in infection-relevant environments, such as cystic fibrosis sputum.

TL;DR: Recent significant advances in mitochondrial chemical biology are highlighted, focusing on the development of chemical tools to perturb mitochondrial biochemistry, probes allowing precise measurement of mitochondrial function, and new techniques for high-throughput characterization of the mitochondrial proteome.