Exploration of the Amadori Rearrangement for Bioconjugation of Carbohydrates

• Applicant: Professorin Dr. Thisbe K. Lindhorst
• Co-Applicant: Professorin Dr.-Ing. Tanja Maria Wrodnigg
• Subject Area: Biological and Biomimetic Chemistry
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 214444592

For the investigation of the multi-facetted biological function of carbohydrates 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 tool to the available bioconjugation methods. The AR allows the formation of an anomerically aminomethyl-functionalized ketose from the respective aldose and a suitable amine under acid catalysis. To date, a broad application of this reaction is not yet feasible, however, the scope of the AR could well comprise a variety of useful conjugation reactions, including mono- as well as polyvalent amines, and functionalized surfaces. Here, the expertise of two groups from Germany and Austria will be combined to elaborate applications of the AR in a selection of highly relevant examples.The applicants propose the following tasks:(1) Broad application of AR to suitable aldoheptoses and a wide range of mono- as well as oligovalent amines.(3) Fabrication of complex glycoconjugates as well as glyco-decorated surfaces employing the AR.(2) Development of a reaction protocol for the AR under physiological conditions in water.(4) Biological evaluation of the D-manno-configured AR products as inhibitors of type 1-fimbriated E. coli bacteria.(5) Introduction of photosensitive substituents, i.a. diazirines and azobenzenes, to obtain photoresponsive materials.(6) Elaboration of achievements in interdisciplinary projects.The collaboration ensures that these aims will be successfully met by combining expertise at “both ends” of the proposal: (i) regarding the synthesis of carbohydrate starting materials and the optimization of reaction conditions for AR, and (ii) relevant amino-functionalized systems that have the potential to open the door into more biologically relevant applications of AR. This transnational funding will enable PhD students to achieve expertise of methodologies from both research groups and broaden their scientific education as well as experience.

• DFG Programme: Research Grants
• International Connection: Austria