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© 2017 The Chemical Society of Japan.Biologically relevant amines react with acrolein to provide 3-formyl-3,4-dehydropiperidine (FDP) as the oxidative stress product, which has reduction potential via hydrogen transfer. This biogenic process was applied to the domino reduction of electron-deficient nitroarenes in one-pot operation, by simply mixing primary amine, acrolein, nitroarene, and calcium chloride. The reaction can be performed in a gram-scale without the use of hazardous metals.

© 2016 The Author(s).Acrolein, a highly toxic α, β-unsaturated aldehyde, has been a longstanding key biomarker associated with a range of disorders related to oxidative stresses. One of the most promising methods for detecting acrolein involves the use of antibodies that can recognize the acrolein-lysine conjugate, 3-formyl-3, 4-dehydropiperidines (FDP), within oxidatively stressed cells and tissues from various disease states. We have uncovered here that FDP could reduce nitroarenes in high yields at 100 °C in the presence of excess CaCl 2 as a Lewis acid promoter. This unique transformation allowed for the development of a de novo method for detecting levels of FDPs generated from proteins in urine or blood serum samples. Thus we successfully converted a non-fluorescent and inexpensive 4-nitrophthalonitrile probe to the corresponding fluorescent aniline, thereby constituting the concept of fluorescent switching. Its sensitivity level (0.84 nmol/mL) is more than that of ELISA assays (3.13 nmol/mL) and is already equally reliable and reproducible at this early stage of development. More importantly, this method is cost effective and simple to operate, requiring only mixing of samples with a kit solution. Our method thus possesses potential as a future alternative to the more costly and operatively encumbered conventional antibody-based methods.

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimA bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.

Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living organisms. A highly conserved carbohydrate binding module, LysM, is found in proteins from viruses, bacteria, fungi, plants and mammals. LysM modules recognize polysaccharides containing N-acetylglucosamine (GlcNAc) residues including peptidoglycan, an essential component of the bacterial cell wall. However, the molecular mechanism underpinning LysM-peptidoglycan interactions remains unclear. Here we describe the molecular basis for peptidoglycan recognition by a multimodular LysM domain from AtlA, an autolysin involved in cell division in the opportunistic bacterial pathogen Enterococcus faecalis. We explore the contribution of individual modules to the binding, identify the peptidoglycan motif recognized, determine the structures of free and bound modules and reveal the residues involved in binding. Our results suggest that peptide stems modulate LysM binding to peptidoglycan. Using these results, we reveal how the LysM module recognizes the GlcNAc-X-GlcNAc motif present in polysaccharides across kingdoms.

© 2014 Elsevier Ltd. All rights reserved. We demonstrated synthetically that the eight-membered heterocycles 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes are the initial and exclusive products of the reaction, through an imino [4+4] cycloaddition, of biologically relevant amines with acrolein. The stabilities of the aminoacetals within the eight-membered heterocycles determined whether the product was subsequently transformed gradually into the 3-formyl-3,4-dehydropiperidine (FDP), which is widely used as an oxidative stress marker. The reactivity profiles discovered in this study suggested that some of the imino [4+4] cycloaddition products are reactive intermediates of FDP and contribute to the mechanisms underlying the oxidative stress response to acrolein.

Nod1 is an intracellular protein that is involved in recognition of bacterial molecules and whose genetic variation has been linked to several inflammatory diseases. Previous studies suggested that the recognition core of Nod1 stimulatory molecules is -D-glutamyl-meso-diaminopimelic acid (iE-DAP), but the identity of the major Nod1 stimulatory molecule produced by bacteria remains unknown. Here we show that bacteria produce lipophilic molecules capable of stimulating Nod1. Analysis of synthetic compounds revealed stereoselectivity of the DAP residue and that conjugation of lipophilic acyl residues specifically enhances the Nod1 stimulatory activity of the core iE-DAP. Furthermore, we demonstrate that lipophilic molecules induce and/or enhance the secretion of innate immune mediators from primary mouse mesothelial cells and human monocytic Mono- Mac6 cells, and this effect is mediated through Nod1. These results provide insight into the mechanism of immune recognition via Nod1, which might be useful in the design and testing of novel immunoregulators.