(2016年11月23日) 报告人：Roland J. Pieters (Utrecht University)

报告题目: Protein Carbohydrate Interactions and Disease

报告人: Roland J. Pieters; Department of Chemical Biology & Drug Discovery; Utrecht Institute for Pharmaceutical Sciences, Utrecht University; P.O.Box 80082, NL-3508 TB Utrecht; The Netherlands

报告时间：2016年11月23日(星期三) 10:00-12:00AM

报告地点：太阳成集团 化学馆120室

报告人简介：Roland Pieters studied organic chemistry at the University of Groningen, the Netherlands (MSc. 1990) where he worked with Prof. Ben Feringa (Nobel prize 2016) and also as an exchange student at Trinity University in San Antonio (USA). He completed his Ph.D. at MIT with Prof. Julius Rebek Jr. in 1995 and was an NWO Talent post-doctoral at the ETH-Zürich with Prof. Francois Diederich. After another post doctoral stay (University of Groningen) he joined Utrecht University as an assistant professor in 1998 and obtained a fellowship from the Royal Netherlands Academy of Arts and Sciences and coordinated the EU project POLYCARB. He became an associate professor in 2005, obtained a VICI grant in 2008, and was promoted to full professor in 2010. His current research interests at the department of Chemical Biology and Drug Discovery are directed towards glycodrugs, by studying the interference with protein-carbohydrate interactions using multivalent systems of varying architectures including those with rigid spacers, and using fragment libraries, for targets such as viral and bacterial adhesion proteins and toxins, galectins and glycosidases, Furthermore his group uses glyco- and peptide-microarrays in chemical biology and drug discovery e.g. on O-GlcNAcylation.

报告摘要：The recognition of carbohydrates by proteins is an important phenomenon in living systems and also plays a role in numerous diseases. Interference with these interactions is an important goal towards drug development. Interference is possible by multivalent carbohydrates that greatly enhance inhibitory potency compared to monovalent inhibitors. Bacterial lectins and toxins have been explored with the goal of optimizing inhibition by optimizing the multivalent presentation of the ligands. The optimization process depends on the orientation of the binding sites and different solutions were fond for the pentavalent cholera toxin [1] in comparison with the functionally divalent adhesion lectin LecA of Pseudomonas aeruginosa [2]. Besides lectins, carbohydrates processing proteins are important and we have studied the inhibition of glycosidases by modified iminosugars. These guanidiniums [3] and pseudo-ureas were particularly portent inhibitors of the human beta-glucocerebrosidase with low nanomolar inhibition. Finally, we are involved in the study of O-GlcNAcylation of serine and threonine residues of proteins. In order to study the addition and removal of GlcNAc moieties we used a peptide microarray and were able to find specific conditions to measure and also inhibit these processes [4].

References

[1] Zomer-van Ommen, D.; Pukin, A.; Fu, O.; Quarles van Ufford, L.; Janssens, H.; Beekman, J.; Pieters, R. J. J. Med. Chem. 2016, 59, 6968-6972.

[2] Visini, R.; Jin, X.; Bergmann, M.; Michaud, G.; Pertici, F.; Fu, O.; Pukin, A.; Branson, T. R.; Thies-Weesie, D. M. E.; Kemmink, J.; Gillon, E.; Imberty, A.; Stocker, A.; Darbre, T.; Pieters, R. J.; Reymond, J.-L. ACS Chemical Biology, 2015, 10, 2455-2462.

[3] Kooij, R.; Branderhorst, H. M.; Bonte, S.; Wieclawska, S.; Martin, N. I.; Pieters, R. J. MedChemComm, 2013, 4, 387-393.

[4] Shi, J.; Sharif, S.; Ruijtenbeek, R.; Pieters, R. J. PLOS One, 2016, 11, e0151085.