Automated solid phase synthesis of oligoarabinofuranosides

Automated solid phase synthesis enables rapid access to the linear and branched arabinofuranoside oligosaccharides. A simple purification step is sufficient to provide the conjugation ready oligosaccharides in good yield

Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans- glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis- glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides

The Breaking Beads Approach for Photocleavage from Solid Support

Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. The photocleavage, usually performed by batch irradiation, suffers from incomplete and slow cleavage. To overcome these issues, continuous flow and high-energy lamps are frequently used, but these setups are hazardous, technically challenging, and expensive. We developed a photocleavage approach that relies on a benchtop LED lamp and magnetic stirring. In this approach, we crush the beads instead of keeping their integrity to increase the yield of photocleavage. This approach proved very efficient for photocleavage of protected oligosaccharides

pH Controlled Impedimetric Sensing of Copper(II) Ion Using Oxytocin as Recognition Element

We report the modulation of the specific metal gation properties of a peptide and demonstrate a highly selective sensor for copper(II) ion. The neuropeptide oxytocin (OT) is reported for its high affinity towards Zn2+ and Cu2+ at physiological pH. The binding of the metal ions to OT is tuned by altering the pH of the medium. OT was self-assembled on glassy carbon electrode using surface chemistry, and electrochemical impedance spectroscopy (EIS) was used to probe the binding of Cu2+. Our results clearly indicate that at pH 10.0, the binding of Cu2+ to OT is increased compared to that at pH 7.0, while the binding to Zn2+ becomes almost negligible. This proves that the selectivity of OT towards each of the ions can be regulated simply by controlling the pH of the medium and hence allows the preparation of a sensing device with selectivity to Cu2+

On Sensing Principles Using Temporally Extended Bar Codes

The detection of ionic variation patterns could be a significant marker for the diagnosis of neurological and other diseases. This paper introduces a novel idea for training chemical sensors to recognise patterns of ionic variations. By using an external voltage signal, a sensor can be trained to output distinct time-series signals depending on the state of the ionic solution. Those sequences can be analysed by a relatively simple readout layer for diagnostic purposes. The idea is demonstrated on a chemical sensor that is sensitive to zinc ions with a simple goal of classifying zinc ionic variations as either stable or varying. The study features both theoretical and experimental results. By extensive numerical simulations, it has been shown that the proposed method works successfully in silico. Distinct time-series signals are found which occur with a high probability under only one class of ionic variations. The related experimental results point in the right direction

A targeted approach for the synthesis of multi-phosphorylated peptides: a tool for studying the role of phosphorylation patterns in proteins

ISSN:1477-0520ISSN:1477-053

Impedimetric Bacterial Detection Using Random Antimicrobial Peptide Mixtures

The biosensing of bacterial pathogens is of a high priority. Electrochemical biosensors are an important future tool for rapid bacteria detection. A monolayer of bacterial-binding peptides can serve as a recognition layer in such detection devices. Here, we explore the potential of random peptide mixtures (RPMs) composed of phenylalanine and lysine in random sequences and of controlled length, to form a monolayer that can be utilized for sensing. RPMs were found to assemble in a thin and diluted layer that attracts various bacteria. Faradaic electrochemical impedance spectroscopy was used with modified gold electrodes to measure the charge-transfer resistance (RCT) caused due to the binding of bacteria to RPMs. Pseudomonas aeruginosa was found to cause the most prominent increase in RCT compared to other model bacteria. We show that the combination of highly accessible antimicrobial RPMs and electrochemical analysis can be used to generate a new promising line of bacterial biosensors

Stirring Peptide Synthesis to a New Level of Efficiency

In this work, a new setup that relies on fast stirring and heating was used to increase the diffusion of both reagents and solid support. we show that the combination of fast mixing and elevated temperature enables the acceleration of solid-phase peptide synthesis without using a large excess of reagents, providing a greener and accessible alternative to the state-of-the-art.<br /

Diffusion Enhanced Amide Bond Formation on Solid Support

Performing amino acids coupling reactions on solid support using fast overhead stirring is far more efficient than the common shaking mixing methods. Stirring does not harm the polystyrene beads and allows to decrease dramatically the amount of reagents used and wasted in these transformations

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support.

Several multistep strategies were developed to ensure single methylation of amines on solid support. These strategies rely on the introduction of the o-NBS protecting/activating group as a key step. We found that the state-of-the-art strategies fail for the methylation of several primary amine motifs, largely due to inefficient sulfonylation. Here we show that using the superior nucleophilic base DMAP instead of the commonly used base collidine as a sulfonylation additive is essential for the introduction of the o-NBS group to these amine motifs. DFT calculations provide an explanation by showing that the energy barrier of the DMAP intermediate is significantly lower than the one of the collidine. We demonstrate that using DMAP as a sole additive in the sulfonylation step results in an overall effective and regioselective N-methylation. The method presented herein proved highly efficient in solid-phase synthesis of a somatostatin analogue bearing three Nα-methylation sites that could not be synthesized using the previously described state-of-the-art methods