Carbohydrates are the most abundant type of biomolecules. However, relatively little is known about the relation between the molecular structure of carbohydrates and their macroscopic properties. In order to shed light on this structure-properties correlation, the method that would enable an access to a variety of carbohydrate structures has to be developed. One of the most promising approaches to achieve this goal is automated solid-phase synthesis. Chapter 2 of this dissertation covers the in-depth analysis and optimization of all the steps of automated glycan assembly, including resin functionalization, elongation cycle and photocleavage process. Several resin loading determination methods have been tested and the method with the best applicability has been chosen. New photo cleavable linkers have been designed and their potential applicability in automated glycan assembly has been investigated. The optimization of the elongation cycle (acidic wash, glycosylation, deprotection steps) in automated glycan assembly has been performed. The time required for the cycle has been significantly reduced (from 170 min to 60 min), the amount of solvents and building blocks used has been decreased that made the overall automated process greener. Chapter 3 describes the application of the optimized conditions to the synthesis of a library of oligo- and polysaccharides. It has been shown that these conditions can be applied to different building blocks and can enable a modular and rapid access to a variety of structures (mannosides, glucosides, glucosaminosides). Molecular modelling studies of the synthesized structures have been performed. It was revealed that hexamers of mannose, glucose and glucosamine have different molecular shape that can lead to differences in their macroscopic properties. Chapter 4 describes the investigation of potential strategies to synthesize glycosaminoglycans. The synthesis of building blocks needed for the synthesis of dermatan and chondroitin sulfate oligosaccharides has been performed. Several strategies for the synthesis of fully deprotected dermatan sulfate oligosaccharides have been tested. The automated synthesis of several dermatan sulfate oligosaccharides has been conducted. The synthesis of several iduronic acid derivatives has been performed. The optimal synthesis conditions for the disulfated iduronic acid, previously found to be a potential inhibitor for CCL20 – heparin sulfate interaction, have been chosen. In conclusion, it is shown that automated glycan assembly enables an access to the library of oligosaccharides that can be used for further structural investigations.
