Main areas of research

  • Development of efficient and reliable synthetic methods for glycomimetics

  • Design and synthesis of iminoalditol based glycosidase inhibitors and pharmacological chaperones

  • Design and construction of iminoalditol based functional surfaces

  • Application of the Amadori rearrangement for the synthesis of functionalised neoglycoconjugates

  • Design and development of iminoalditol base glycoprobes for activity based protein profiling of carbohydrate processing enzymes

 

 

Selected applications

 

Glycomimetics, such as iminosugars, have been introduced as pharmacological chaperones for the chaperone mediated therapy (CMT) of a range of hereditary lysosomal storage diseases (LSD), complementing enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). CMT is expected to be a new powerful alternative for the long-term treatment of neurodegenerative symptoms of LSDs.

 

With our synthetic approaches, we do have straight forward access to N-modified as well as C-glycosyl type piperidine and pyrrolidine derived glycomimetics in different configurations of the sugar moiety, such as d-gluco, d-galacto, l-ido, d-manno, 2-acetamido-d-gluco as well as d-xylo, d-arabino, d-manno, respectively. Based on pieces of structural information on glycoside processing enzymes, functionally modified iminosugars can be designed which have potential as pharmacological chaperones for the treatment of LSDs such as Gaucher´s disease, GM1-gangliosidosis, Sandhoff and Tay-Sachs diseases.

The Amadori rearrangement of aldoheptoses is leading to neuoglycoconjugates.

A big variety of different amines including diamines, amino-functionalized glycosides, lysine derivatives and peptides can be employed in this rearrangement leading to chemically stable adducts without the need of protecting group manipulations. Such type of compounds find different applications, for example they are ligands for lectins applicable in anti-adhesion therapy of bacterial infections, they are useful building blocks for glycopeptide synthesis, as well as for the construction of glycopolymers, -dendrimers and –clusters. Consequently, this method is a tool for chemoselective protein modification.