On-Chip Neo-Glycopeptide Synthesis for Multivalent Glycan Presentation

Single glycan–protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser-based array synthesis technology allows for flexible and rapid on-surface synthesis of different peptides. By combining this technique with click chemistry, neo-glycopeptides were produced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well-defined glycan structures for multivalent display. The two lectins concanavalin A and langerin were probed with different glycans on multivalent scaffolds, revealing strong spacing-, density-, and ligand-dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding.     

Through-Space Polar-π Interactions in 2,6-Diarylthiophenols

Molecular recognition between polar groups and aromatic molecules is fundamentally important to rational drug design. Although it has been well established that many polar functionalities interact with electron-rich aromatic residues through energetically favorable polar-π interactions, there is a limited understanding of the association between thiols and aromatic systems. Herein we report physical-organic chemistry studies on 2,6-diarylthiophenols that possess the central thiophenol ring and two flanking aromatic rings with tunable electronic properties caused by substituents at distant para position. Hammett analysis revealed that pK_a values and proton affinities correlate well with Hammett sigma values of substituents. Additional energy decomposition analysis supported the conclusion that both through-space SH-π interactions and S⁻-π interactions contribute to intramolecular stabilization of 2,6-diarylthiophenols.     

Gold-Catalyzed C(sp2)−C(sp) Coupling by Alkynylation through Oxidative Addition of Bromoalkynes

A gold(I)-catalyzed cascade cyclization–alkynylation of allenoates using alkynyl bromide to generate β-alkynyl-γ-butenolides was investigated. Whereas alkynyl iodides afforded significant amounts of the homo-coupling of two lactone units, alkynyl bromides led to a selective reaction, and a broad functional group tolerance was observed. Under the optimized reaction conditions, it was possible to directly synthesize a large range of β-alkynyl-γ-butenolides in moderate to good yields without the need for any external oxidant.     

Rhodamines with a Chloronicotinic Acid Fragment for Live Cell Superresolution STED Microscopy**

Formylation of 2,6-dichloro-5-R-nicotinic acids at C-4 followed by condensation with 3-hydroxy-N,N-dimethylaniline gave analogs of the popular TAMRA fluorescent dye with a 2,6-dichloro-5-R-nicotinic acid residues (R=H, F). The following reaction with thioglycolic acid is selective, involves only one chlorine atom at the carbon between pyridine nitrogen and the carboxylic acid group and affords new rhodamine dyes absorbing at 564/ 573 nm and emitting at 584/ 597 nm (R=H/ F, in aq. PBS). Conjugates of the dyes with “small molecules” provided specific labeling (covalent and non-covalent) of organelles as well as of components of the cytoskeleton in living cells and were combined with fluorescent probes prepared from 610CP and SiR dyes and applied in two-color STED microscopy with a 775 nm STED laser.     

Torus Actions in the Normalization Problem

Let f be a germ of biholomorphism of ℂ ⁿ , fixing the origin. We show that if the germ commutes with a torus action, then we get information on the germs that can be conjugated to f, and furthermore on the existence of a holomorphic linearization or of a holomorphic normalization of f. We find out in a complete and computable manner what kind of structure a torus action must have in order to get a Poincaré-Dulac holomorphic normalization, studying the possible torsion phenomena. In particular, we link the eigenvalues of df _O to the weight matrix of the action. The link and the structure we found are more complicated than what one would expect; a detailed study was needed to completely understand the relations between torus actions, holomorphic Poincaré-Dulac normalizations, and torsion phenomena. We end the article giving an example of techniques that can be used to construct torus actions.