Symmetric dithiodigalactoside: strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins

Thioglycosides offer the advantage over O-glycosides to be resistant to hydrolysis. Based on initial evidence of this recognition ability for glycosyldisulfides by screening dynamic combinatorial libraries, we have now systematically studied dithiodigalactoside on a plant toxin (Viscum album agglutinin) and five human lectins (adhesion/growth-regulatory galectins with medical relevance e.g. in tumor progression and spread). Inhibition assays with surface-presented neoglycoprotein and in solution monitored by saturation transfer difference NMR spectroscopy, flanked by epitope mapping, as well as isothermal titration calorimetry revealed binding properties to VAA (Ka: 1560 ± 20 M-1). They were reflected by the structural model and the affinity on the level of toxin-exposed cells. In comparison, galectins were considerably less reactive, with intrafamily grading down to very minor reactivity for tandem-repeat-type galectins, as quantitated by radioassays for both domains of galectin-4. Model building indicated contact formation to be restricted to only one galactose moiety, in contrast to thiodigalactoside. The tested lycosyldisulfide exhibits selectivity between the plant toxin and the tested human lectins, and also between these proteins. Therefore, glycosyldisulfides have potential as chemical platform for inhibitor design

A Photochemically Initiated Chemistry for Coupling Underivatized Carbohydrates to Gold Nanoparticles

The sensitive optoelectronic properties of metal nanoparticles make nanoparticle-based materials a powerful tool to study fundamental biorecognition processes. Here we present a new and versatile method for coupling underivatized carbohydrates to gold nanoparticles (Au NPs) via the photochemically induced reaction of perfluorophenylazide (PFPA). A one-pot procedure was developed where Au NPs were synthesized and functionalized with PFPA by a ligand-exchange reaction. Carbohydrates were subsequently immobilized on the NPs by a fast light activation. The coupling reaction was efficient, resulting in high coupling yield as well as high ligand surface coverage. A colorimetric system based on the carbohydrate-modified Au NPs was used for the sensitive detection of carbohydrate-protein interactions. Binding and cross-reactivity studies were carried out between carbohydrate-functionalized Au NPs and lectins. Results showed that the surfacebound carbohydrates not only retained their binding affinities towards the corresponding lectin, but also exhibited affinity ranking consistent with that of the free ligands in solution

Rapid, regioselective deuteration of dimethyl-2,2'-bipyridines via microwave-assistance

Isotopically pure [D6]-dimethyl-2,2′-bipyridine derivatives were selectively and rapidly formed using microwave-assisted regioselective deuteration of the methyl moieties of the parent bipyridine in a deuterium oxide solution. For instance, [D6]-4,4′-dimethyl-2,2′-bipyridine was formed in quantitative yield within 15 minutes, in a simple and convenient process.QC 20151119</p

Polymerization, Stimuli-induced Depolymerization, and Precipitation-driven Macrocyclization in a Nitroaldol Reaction System

Dynamic covalent polymers of different topology have been synthesized from an aromatic dialdehyde and alpha,omega-dinitroalkanes via the nitroaldol reaction. All dinitroalkanes yielded dynamers with the dialdehyde, where the length of the dinitroalkane chain played a vital role in determining the structure of the final products. For longer dinitroalkanes, linear dynamers were produced, where the degree of polymerization reached a plateau at higher feed concentrations. In the reactions involving 1,4-dinitrobutane and 1,5-dinitropentane, specific macrocycles were formed through depolymerization of the linear chains, further driven by precipitation. At lower temperature, the same systemic self-sorting effect was also observed for the 1,6-dinitrohexane-based dynamers. Moreover, the dynamers showed a clear adaptive behavior, displaying depolymerization and rearrangement of the dynamer chains in response to alternative building blocks as external stimuli

Molecularly Imprinted Polymeric Adsorbents for Byproduct Removal

In this study, both diastereo- and enantioselective adsorbents for a dipeptide derivative were prepared using a molecular imprinting technique. The diastereo- and enantioisomers for the dipeptide derivative N-(benzyloxy-carbonyl)aspartylphenylalanine methyl ester (ZAPM), in addition to the α- and β-isomers, were chosen as test compounds for the investigation of the imprinting effect The close similarities between the structures of different isomers make it possible to interpret the roles of template structure on specific molecular recognition. A highly specific byproduct scavenger was prepared by simultaneously incorporating methacrylic acid and vinylpyridine as functional monomers. The binding selectivities of polymeric adsorbents for the α- and β-isomers are shown to be greatly enhanced by introducing enantiocomplementarities into the polymer matrixes. An anti-β-L,L-ZAPM polymer was applied in a solid-phase extraction protocol, for the purification of the product in the chemical synthesis of N-protected aspartame. Finally, polymer beads were also imprinted against β-L,L-ZAPM using suspension polymerization performed in perfluorocarbon fluid. The imprinted polymer beads displayed the same binding characteristics as the imprinted bulk polymer and can be envisaged for the use of product purification in chromatographic mode