Design, synthesis, and characterization of stapled oligosaccharides

Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not been applied to oligosaccharides. Here, we describe the design, synthesis, and characterization of the first stapled oligosaccharides. Automated assembly of β-(1,6)-glucans equipped with two alkenyl side chains was followed by on-resin Grubbs metathesis for efficient ring closure with a variety of cross-linkers of different sizes. Oligosaccharide stapling increases enzymatic stability and cell penetration, therefore opening new opportunities for the use of glycans in medicinal chemistry

Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers

Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine “click”-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar “raft-like” nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity. © 2020 National Academy of Sciences. All rights reserved

Synthesis of meta and para-substituted aromatic sulfonate derivatives of polydentate phenylazaphosphinate ligands: enhancement of the water solubility of emissive europium(III) EuroTracker® dyes

The synthesis is described of a series of meta and para-substituted phenylsulfonate derivatives of very bright Eu(III) complexes with arylphosphinate groups and strongly absorbing arylalkynylpyridine moieties. The synthetic route involved the early introduction of trifluoroethyl esters to protect the sulfonic acid group, withstanding the use of reagents including acetyl bromide and mCPBA, and tolerating acid-catalysed esterification and Sonogashira reaction conditions. The Eu(III) complexes exhibit enhanced water solubility; their photophysical properties are not perturbed significantly by introduction of the anionic sulfonate groups

Elastic behaviour and structural evolution of nanocrystalline Fe73.5Cu1Nb3Si13.5B9 produced by thermal ageing or joule-heating

Internal friction and dynamic Young's modulus versus temperature were measured in Fe73.5Cu1Nb3Si13.5B9 melt-spun ribbons as-prepared or after being submitted to Joule-heating treatments or to furnace annealing during isothermal modulus measurements. In Joule-heated samples the resistance was measured continuously during the heating treatments. Changes in the resistivity reflecting changes in the microstructure were correlated with room-temperature measurements of the magnetic permeability and the Delta E effect. The experimental results are discussed with specific reference to the microstructural evolution of the annealed ribbons from the initial amorphous phase to the nanocrystalline phase. A strong enhancement of the Delta E effect was found in Joule-heated ribbons just before the nanocrystalline phase formed

EFFECT OF SYNTHETIC TACHYKININ ANALOGS ON AIRWAY MICROVASCULAR LEAKAGE IN RATS AND GUINEA-PIGS - EVIDENCE FOR THE INVOLVEMENT OF NK-1 RECEPTORS

Selective neurokinin receptor agonists provided evidence that the inflammatory response to intravenous tachykinins is exclusively mediated by the NK1 receptor subtype. Preliminary evidence was also drawn that, after depletion of transmitters from the capsaicin-sensitive nerves, upregulation of NK1 receptors may develop in the rat trachea

REGIONAL DIFFERENCES IN THE MOTOR AND INFLAMMATORY RESPONSES TO CAPSAICIN IN GUINEA-PIG AIRWAYS - CORRELATION WITH CONTENT AND RELEASE OF SUBSTANCE-P-LIKE IMMUNOREACTIVITY

Motor and inflammatory effects of capsaicin, SP and NKA were investigated in guinea pig airways, as well as the content and release of SP-LI. Capsaicin effects were greater in lower airways, while tachykinins produced similar effects at tracheal and bronchial levels. Regional differences in the response of guinea pig respiratory tissues to activation of capsaicin-sensitive sensory fibres might be prejunctional in origin

EuroTracker® dyes : design, synthesis, structure and photophysical properties of very bright europium complexes and their use in bioassays and cellular optical imaging

The development of the brightest luminescent europium(III) complexes is traced, including analysis of the C3-symmetric core complex based on a functionalized triazacyclononane and identification of the most suitable strongly absorbing chromophore. Strategies for the synthesis of the complexes, including enantiopure analogues, are outlined and opportunities for applications in time-resolved microscopy and spectral imaging emphasised. Practicable examples are introduced, including selective organelle staining for cellular optical imaging at 65 nm resolution and the development of new bioassays using time-resolved FRET methods