The research interests represent a well-balanced blend of organic and biological chemistry, addressing in particular modern aspects of medicinal chemistry. The conducted research includes development of new drug/target discovery methods and organic synthesis of new biochemical tools, as well as their application to biologically relevant processes.
One of the main studies in the group is the discovery and investigation of biologically relevant receptors. Investigation of receptor-ligand interactions remains an inexhaustible challenge for chemistry and biology. For example, carbohydrate binding proteins are the focus of present attention due to recent realization that they act as recognition determinants in diverse biological processes. It is assumed that carbohydrates have an enormous potential for encoding biological information and, most probably, carbohydrate binding proteins are suited as decoders of this carbohydrate-encoded information. Today researchers face the impressive challenge of assigning molecular and cellular function to the tremendous number of carbohydrate binding proteins and carbohydrates. The goal of this projects is to develop new tools for the selective labeling of receptors in complex mixtures.
Protein-protein interactions are central to many biological processes, and they represent a large and important class of targets for human therapeutics. However, modulating protein-protein interactions with small, drug-like molecules is, in general, extremely difficult due to issues such as the lack of well-defined binding pockets on the protein surfaces. Currently, there are no general techniques or approaches for the development of potent and effective, drug-like, protein-protein interaction modulators (PPIMs). The aim of this study is to introduce a reliable strategy for the discovery and development of PPIMs. This strategy relies on a kinetically controlled target-guided synthesis approach, which uses the target protein itself to synthesize a divalent ligand by equilibrium-controlled sampling of reagents carrying complementary reactive functionalities until an irreversible reaction connects the pair that best fits the protein's binding pockets. Function evolves in the presence of the target protein as a provided pool of complementary self-reactive building blocks scan for binding opportunities over the surface of the protein, remaining on the spots offering the highest affinity. This searching process ends when two blocks irreversibly form a divalent molecule, thereby locking in information about the target protein which recruited them.