Mechanical strain stimulates COPII-dependent secretory trafficking via Rac1.

Cells are constantly exposed to various chemical and physical stimuli. While much has been learned about the biochemical factors that regulate secretory trafficking from the endoplasmic reticulum (ER), much less is known about whether and how this trafficking is subject to regulation by mechanical signals. Here, we show that subjecting cells to mechanical strain both induces the formation of ER exit sites (ERES) and accelerates ER-to-Golgi trafficking.

Easy Production of "Difficult Peptides" Using Cell-Free Protein Synthesis and a New Methionine Analogue as a Latent Peptide Cleavage Site.

Aliphatic γ-chloro-α-amino acids incorporated in place of their canonical analogues through cell-free protein synthesis act as heat-labile linkers, offering a useful strategy for the straightforward production of target peptides as fusion proteins, from which the targets are readily released. Until now, the natural abundance of aliphatic amino acids in peptides has limited the scope of the method, as it leads to undesired cleavage sites in synthesized products, but here the authors report the development of a new cleavable chloro amino acid that incorporates in place of the relatively rare amino acid methionine, thus greatly expanding the scope of producible targets. This new strategy is employed for simplified peptide synthesis with a methionine-free fusion partner, allowing single-site incorporation of the cleavable linker for clean release and easy purification of the target peptide.

Systematic Investigation of Resorcin[4]arene-Based Cavitands as Affinity Materials on Quartz Crystal Microbalances.

Resorcin[4]arene cavitands are well-known supramolecular hosts, and their outstanding guest-binding abilities in solution have been studied in detail in recent decades. In a systematic approach, different resorcin[4]arene cavitands and container molecules are characterized as affinity materials for gravimetric sensing using high-fundamental-frequency quartz crystal microbalances. Analysis of their affinity toward a series of various analytes reveals a remarkable dependence of both selectivity and sensitivity on the shape, accessibility, and size of the cavity, along with their supramolecular interactions with the host molecules.

Cycloalkane and alicyclic heterocycle complexation by new switchable resorcin[4]arene-based container molecules: NMR and ITC binding studies.

The synthesis and structural characterization of novel, "molecular basket"-type bridged cavitands is reported. The resorcin[4]arene-based container molecules feature well-defined cavities that bind a wide variety of cycloalkanes and alicyclic heterocycles. Association constants (K(a)) of the 1:1 inclusion complexes were determined by both (1)H NMR and isothermal titration calorimetry (ITC).

Improved inhibitors of trypanothione reductase by combination of motifs: synthesis, inhibitory potency, binding mode, and antiprotozoal activities.

Trypanothione reductase (TR) is an essential enzyme in the trypanothione-based redox metabolism of trypanosomatid parasites. This system is absent in humans and, therefore, offers a promising target for the development of selective new drugs against African sleeping sickness and Chagas' disease. Over the past two decades, a variety of nonpeptidic small-molecule ligands of the parasitic enzyme were discovered.