HIPS-Talk “Carbohydrate-lectin interactions – What makes them unique?”
Over the last two decades, a wealth of physiological and pathophysiological functions related to carbohydrate-lectin interactions have been uncovered. However, only a fraction of these discoveries have led to new therapeutic concepts.
The reasons are manifold: first, carbohydrates are generally regarded as highly demanding lead structures because of their notoriously insufficient pharmacodynamic (PD) properties, as well as their nondrug-like pharmacokinetic (PK) profiles. In addition, lectins typically exhibit solvent-exposed, extended binding sites, and are therefore often
considered to be undruggable targets.
However, an improved understanding of the principles controlling carbohydrate-lectin interactions have recently led to a number of promising preclinical and clinical candidates, e.g. for the therapy of inflammation, cancer, and viral and bacterial infections.In this lecture, the various pharmacodynamic and pharmacokinetic drawbacks traditionally associated with lectin targets will be discussed, using specific examples from selectin and bacterial lectin targets.
In the second part, solutions to these PK/PD drawbacks will be presented,
exemplified by approaches leading to glycomimetics with nanomolar affinity as well
as drug-like pharmacokinetic properties.
Building and room
Blg E8.1, Seminar Room (Ground Floor)
Prof em Dr Beat Ernst
University of Basel
Beat Ernst studied chemistry at the ETH in Zürich and compiled his Ph.D. thesis entitled "Novel Tricyclic C10-, C11- and C12-Hydrocarbons" under the guidance of Professor Oskar Jeger and Professor Camille Ganter. In 1979, he joined the group of Professor Robert E. Ireland / Californian Institute of Technology in Pasadena as a postdoctoral fellow where he completed the total synthesis of tirandamycic acid. In 1981, he joined the Central Research Laboratories of Ciba-Geigy Ltd. in Basel, became group leader in 1983 and head of the section Carbohydrate Chemistry and Biology in 1992. After the merger of CIBA and SANDOZ in 1996, he moved to the therapeutic area Transplantation, where he was heading the program "Selectin Antagonists". In October 1998, he accepted a position as Professor of Molecular Pharmacy at the University of Basel. His research interests are the chemical and enzymatic synthesis of therapeutically promising oligosaccharides and mimetics thereoff and the investigation of carbohydrate/protein interactions by NMR, surface
plasmon resonance, microcaloimetry, and molecular modeling.
Prof. Dr. Anna Hirsch