FWF - Sugar-Conjugates - Exploration of the Amadori Rearrangement for Bioconjugation of Carbohydrates

For the investigation of the multi-facetted biological function of carbohydrates, which are ubiquitously found on cell surfaces as well as in soluble glycoconjugates, reliable methods to ligate saccharides to biomolecules and to specific labels are required. For many applications it is essential that such ligation chemistries are functional in an aqueous medium and without the requirement of protecting groups on the carbohydrate part - a considerable challenge in synthetic chemistry. It is the aim of this project to explore the Amadori rearrangement (AR) for the bioconjugation of saccharides to amines in order to add a new "natural" tool to the available bioconjugation methods. To date, a broad application of this reaction is not available, however, according to its mechanism, the scope of the Amadori rearrangement could well comprise a variety of useful conjugation reactions, including mono- as well as oligo- and polyvalent amines, and the carbohydrate decoration of functionalized surfaces. Here, the expertise of two groups from Germany and Austria will be combined to elaborate applications of the Amadori rearrangement in a selection of highly relevant examples. The tasks for the Austrian team of this application includes: Development of a reliable protocol for employment of mono- as well as oligovalent amines to the Amadori rearrangement of suitable aldoheptoses. Fabrication of complex glycoconjugates as well as glyco-decorated surfaces employing the AR. Development of reaction protocol of the AR under physiological conditions in water. Introduction of photosensitive substituents, i.a., diazirines and azobenzenes to an aldose starting material in order to obtain photoresponsive materials. By this strategy C-glycosidic linkages between the carbohydrate moiety and the aglycon part will be provided, which are known to be more stable against hydrolysis than the natural O- and N-linkages. Such structures can be embedded as monomeric units for the synthesis of glycopolymers, glycoclusters as well as -dendrimers. Furthermore decoration with a variety of reporter groups such as fluorescent dyes, affinity labels and other substituents as required for biological applications can be achieved easily by the developed method. Additionally, the concept will be investigated for the utility as site-selective peptide modification. The glycoconjugates synthesised in this project will be biologically evaluated as inhibitors of type 1-fimbriated E. coli bacteria by Prof. Lindhorst (Christiana Albertina University, Kiel, Germany). The method developed in this project will contribute a strategy to the repertoire of synthetic access of glycoconjugates mimetics and thereby extend the tool box of possible structures for promoting investigations in the field of Glycoscience in a variety of different research fields.