Seminar: Prof. Herman Overkleeft (hosted by Prof. Romano Orru)

02/19/2018

16.00 - 17.00h

12E65, O|2 Lab Building

Seminar: Activity-based Glycosidase Profiling in Biomedicine and Biotechnology

Prof. Herman Overkleeft (Leiden Institute of Chemistry)

Amsterdam Institute for Molecules, Medicines and Systems

Sciences

Conference / Symposium

Herman_Overkleeft_pictureProf. Herman Overkleeft (Leiden Institute of Chemistry) will provide a Seminar on 19 February entitled 'Activity-based Glycosidase Profiling in Biomedicine and Biotechnology'. The seminar is hosted by Prof. Romano Orru.

You are all cordially invited!

Abstract

Activity-based protein profiling (ABPP) is a rapidly emerging field in chemical biology research. Enzymes that employ a mechanism in processing their substrate that involves formation of a covalent enzyme-intermediate adduct can be blocked by mechanism-based suicide inhibitors: compounds that react within the enzyme active site to form a covalent and irreversible adduct. Introduction of a reporter moiety (‘TAG’ in the below picture) yields an activity-based probe (ABP) through which enzyme activities can be discovered (comparative ABPP) and the efficacy enzyme inhibitors in complex biological systems analyzed (competitive ABPP).

 Herman_Overkleeft_abstract

His work on ABPP development focuses on retaining glycosidases: hydrolytic enzymes able to cleave interglycosidic linkages and that do so through the formation of covalent enzyme-substrate intermediates. Configurational and functional analogues of the natural product and mechanism-based retaining beta-glucosidase inhibitor, cyclophellitol, prove to be highly versatile tools to study retaining glycosidases of various nature and origin in relation to human health and disease, but also in the field of biotechnology. In this seminar, the current state in the design, synthesis and application of synthetic cyclophellitol derivatives in studying retaining glycosidases will be presented.

Discussed subjects will include 1) diagnosis of human lysosomal exoglycosidases in relation to lysosomal storage disorders; 2) glycosylation of cyclophellitol derivatives top arrive at retaining endoglycosidase ABPs and 3) application of glycosidase ABPs in the functional profiling of fungal secretomes for the discovery of glycosidases for biotechnology application.

References

- M. D. Witte, W. W. Kallemeijn, J. Aten, K.-Y. Li, A. Strijland, W. E. Donker-Koopman, B. Blijlevens, G. Kramer, A. M. C. H. van den Nieuwendijk, B. I. Florea, B. Hooibrink, C. E. M. Hollak, R. Ottenhoff, R. G. Boot, G. A. van der Marel, H. S. Overkleeft and J. M. F. G. Aerts, Ultrasensitive in situ visualization of active glucocerebrosidase molecules, Nat. Chem. Biol.2010, 6, 907-913.

- J. Jiang, C.-L. Kuo, L. Wu, C. Franke, W. W. Kallemeijn, B. I. Florea, E. van Meel, G. A. van der Marel, J. D. C. Codée, R. G. Boot, G. J. Davies, H. S. Overkleeft and J. M. F. G. Aerts, Detection of active mammalian GH31 alpha-glucosidases in health and disease using in-class, broad-spectrum activity-based probes, ACS Cent. Sci.2016, 2, 351-358.

- L. Wu, J. Jiang, Y. Jin, W. W. Kallemeijn, C.-L. Kuo, M. Artola, W. Dai, C. van Elk, M. van Eijk, G. A. van der Marel, J. D. C. Codée, B. I. Florea, J. M. F. G. Aerts, H. S. Overkleeft and G. J. Davies, 2017, DOI: 10.1038/NCHEMBIO.2395