Oligosacchrides synthesis and applications

We develop automated approaches for the synthesis of complex oligosaccharides. We use the uniqe Glyconeer synthesizer to enable us to access oligosacchrides in record yield and speed. We use well defined sulfated saccharides for sensing  heavy metal ions in solutions. 

·         AGA

Carbohydrates, also known as glycans or saccharides, are the most abundant biopolymer in nature. Oligosaccharides are short glycans that have multiple biological functions that are derived from their composition, size, and specific linkages architecture. Synthesis of oligosaccharides is the best way to study their interactions and to develop a variety of applications. The synthesis of oligosaccharides is very complicated as it requires installing multiple linkages between the monomers with precise stereo and regio-selectivity. We develop an automated approach to synthesize oligosaccharides. In this effort, we study the role of protecting groups in the formation of glycosidic linkages and participate in the global endeavor to find the optimal building blocks and conditions to facilitate the accessibility to those elusive entities.

·         Photochemistry

Photochemical reactions are Intriguing synthetic transformations. The ability to use light sources with highly defined energy thereby create and break chemical bonds is extremely valuable in organic chemistry. Our group develops and uses photolabile protecting groups and linkers for carbohydrate chemistry. We have been manipulating photolabile protecting groups of various glycans and showed that using 365 nm LED light we can remove a large number of them simultaneously in a very short time. We use photolabile linkers to connect between the glycan and the solid support which is used for automated glycan assembly. We develop fast and efficient strategies to cleave the glycan from the support using light irradiation. We continue and develop this technology to provide a high yield alternative to common cleavage and protecting group methods.

·         sulfated glycans

Sulfated saccharides are enigmatic and highly abundant molecules. They play a massive role in the extracellular matrices of our cells and also in many other organisms such as algae plants and more. Sulfated saccharides take a key part in the interaction between cells and in recognition events. The sulfation of saccharides provides them with new properties that influence their biological function. Sulfation patterns are highly versatile, they are related to specific origin and tissue and are highly sensitive to environmental changes, toxic entities. and many more. We develop tools to synthesize and study the interactions of sulfated saccharides. We use a specific protecting group’s hierarchy to enable the assembly of oligosaccharides with distinctive sulfation patterns. We harness our know-how in glycosylation and solid-phase strategies to automate the synthesis of sulfated saccharides. In parallel, we develop new electrochemical tools to study the interactions of these saccharides. We focus on elucidating the effect of sulfation patterns of metal ion interactions and metal ion mediated protein interactions.

·         Sialosides

Sialic acids are special negatively charged nine-carbon monosaccharides. Sialic acids decorate O- , N –glycans, and gangliosides. Sialic acids play a crucial role in cellular recognition, interactions, and adhesion. Sialylation and desialylation, the assembly or removal of sialic acids, are crucial enzymatic transformations. The function of these enzymes is associated with disease state, pathogen invasion, neuro- and immuno-diseases, and genetic disorders. Because the accessibility to well-defined sialylated glycans, sialosides, is very limited, the biological role and the specific interaction between sialosides and sialylation-related enzymes is understudied. We combine surface chemistry strategies, electrochemical sensing methods, and synthetic know-how to build new tools to study the interactions of sialosides and related enzymes and binding proteins. The developments of these tools bring us closer to finding new inhibitors and treatments for sialic acid-related virus infection.

Peptide synthesis applications

We combine engineering and synthetic concept to improve solid phase synthesis efficeincy. Our approach rely on fast stirring to allow for enhences and green reaction processes.

·         Accelerated peptide synthesis

Peptides are very useful tools for studying proteins function and in applications development. The synthesis of peptides today is ungreen and relatively slow. It requires the use of a high amount of reagents and solvents and usually requires expensive machinery to increase the process efficiency. We develop new ways to accelerate solid-phase peptide synthesis processes. We do that while maintaining low molar equivalents thereby make the synthesis economic and more environmentally friendly. We optimize the synthesis, change the reagents, the conditions, and even redesign the reactor architecture to find the most efficient way to synthesize peptides, glycopeptides, phosphorylated peptides, and more..

·         Phosphorylation

Phosphorylation has a high impact on protein structure, function, and interactions. This highly abundant modification can be found in various positions on the proteins and in different patterns. When the phosphorylation pattern of the same protein changes it creates proteoforms with different functionality and interaction preferences. We develop tools to synthesize multiphosphorylated peptides. These special entities enable us to elucidate the exact function and binding preferences that are dictated by the distinctive phosphorylation code. We use new solid-phase synthesis strategies to automated and accelerate the synthesis libraries of multiphosphorylated peptides.

·         Peptide based biosensors

Peptides are versatile bioactive entities with unique properties. Because of the variety of building blocks and the ease of synthesis they serve as fantastic tools in the development of biosensors. The specific activity and affinity of peptides can be tailored by introducing synthetic modifications and that can be easily equipped with a functional handle that enables attachment to surfaces. We use peptides as a recognition layer and harness their native binding selectivity to produce biosensors for metal ions and enzymatic reactions which can be used to monitor diseases such as multiple sclerosis and cancer.