Activity-Based Profiling of Glycoprocessing Enzymes for Human Health and a Sustainable Society

Project Information

CARBOCENTRE

Grant agreement ID: 951231

DOI

10.3030/951231

EC signature date 18 December 2020

Start date 1 June 2021

End date 31 May 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 9 057 250,00

EU contribution

€ 9 057 250,00

Coordinated by

UNIVERSITEIT LEIDEN
Netherlands

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Publications

Peer reviewed articles (40)

Precision Activity‐Based α‐Amylase Probes for Dissection and Annotation of Linear and Branched‐Chain Starch‐Degrading Enzymes

Author(s): Isabelle B. Pickles, Yurong Chen, Olga Moroz, Haley A. Brown, Casper de Boer, Zachary Armstrong, Nicholas G. S. McGregor, Marta Artola, Jeroen D. C. Codée, Nicole M. Koropatkin, Herman S. Overkleeft, Gideon J. Davies
Published in: Angewandte Chemie International Edition, Issue 64, 2025, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.202415219

Control of Substrate Conformation by Hydrogen Bonding in a Retaining β-Endoglycosidase

Author(s): Alba Nin-Hill, Albert Ardevol, Xevi Biarnés, Antoni Planas, Carme Rovira
Published in: Chemistry—A European Journal, Issue 29, 2023, Page(s) e202302555, ISSN 1521-3765
Publisher: Wiley-VCH GmbH
DOI: 10.1002/chem.202302555

Reaction Mechanism of Glycoside Hydrolase Family 116 UtilizesPerpendicular Protonation

Author(s): Salila Pengthaisong, Beatriz Piniello, Gideon J. Davies, Carme Rovira, and James R. Ketudat Cairns
Published in: ACS Catalysis, Issue 13, 9, 2023, Page(s) 5850–5863, ISSN 2155-5435
Publisher: American Chemical Society
DOI: 10.1021/acscatal.3c00620

Human O-GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics

Author(s): Martín Calvelo, Alexandra Males, Matthew G. Alteen, Lianne I. Willems, David J. Vocadlo, Gideon J. Davies and Carme Rovira
Published in: ACS Catalysis, Issue 13, 20, 2023, Page(s) 13151-13845, ISSN 2155-5435
Publisher: American Chemical Society
DOI: 10.1021/acscatal.3c02378

Constrained Catalytic Itinerary of a Retaining 3,6‐Anhydro‐D‐Galactosidase, a Key Enzyme in Red Algal Cell Wall Degradation

Author(s): Michael D. Wallace, Irene Cuxart, Thomas Roret, Laura Guée, Aleksandra W. Debowski, Mirjam Czjzek, Carme Rovira, Keith A. Stubbs, Elizabeth Ficko‐Blean
Published in: Angewandte Chemie International Edition, 2024, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.202411171

Trans-cyclosulfamidate mannose-configured cyclitol allows isoform-dependent inhibition of GH47 α-d-mannosidases through a bump–hole strategy

Author(s): Alexandra Males, Ken Kok, Alba Nin-Hill, Nicky de Koster, Sija van den Beukel, Thomas J. M. Beenakker, Gijsbert A. van der Marel, Jeroen D. C. Codée, Johannes M. F. G. Aerts, Herman S. Overkleeft, Carme Rovira, Gideon J. Davies, and Marta Artola
Published in: Chemical Science, Issue 14, 2023, Page(s) 13581–13586, ISSN 1478-6524
Publisher: Royal Society of Chemistry
DOI: 10.1039/d3sc05016e

An Orthogonally Protected Cyclitol for the Construction of Nigerose- and Dextran-Mimetic Cyclophellitols.

Author(s): Tim P Ofman; Florian Küllmer; Gijsbert A. van der Marel; Jeroen D. C. Codée; Herman S. Overkleeft
Published in: Organic Letters, 23(24), 9516 - 9519, Issue 23 (24), 2021, Page(s) 9516-9519, ISSN 1523-7060
Publisher: American Chemical Society
DOI: 10.1021/acs.orglett.1c03723

Design and Synthesis of Exocyclic Cyclitol Aziridines as Potential Mechanism-Based Glycosidase Inactivators

Author(s): Tim P. Ofman, Prof. Dr. Gijsbert A. van der Marel, Prof. Dr. Jeroen D. C. Codée, Prof. Dr. Hermen S. Overkleeft
Published in: European Journal of Organic Chemistry, Issue 26,16, 2023, Page(s) e202300186, ISSN 1099-0690
Publisher: Wiley-VCH GmbH
DOI: 10.1002/ejoc.202300186

Bespoke Activity-Based Probes Reveal that the <i>Pseudomonas aeruginosa</i> Endoglycosidase, PslG, Is an Endo-β-glucanase

Author(s): Gijs Ruijgrok, Wendy A. Offen, Isabelle B. Pickles, Deepa Raju, Thanasis Patsos, Casper de Boer, Tim Ofman, Joep Rompa, Daan van Oord, Eleanor J. Dodson, Alexander Beekers, Thijs Voskuilen, Michela Ferrari, Liang Wu, Antonius P. A. Janssen, Jeroen D. C. Codée, P. Lynne Howell, Gideon J. Davies, Herman S. Overkleeft
Published in: Journal of the American Chemical Society, Issue 147, 2025, Page(s) 8578-8586, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.4c16806

Activity-based protein profiling reveals dynamic substrate-specific cellulase secretion by saprotrophic basidiomycetes

Author(s): Nicholas G. S. McGregor; Casper de Boer; Mikhaaeel Santos; Mireille Haon; David Navarro; Sybrin Schroder; Jean-Guy Berrin; Herman S. Overkleeft; Gideon J. Davies
Published in: Biotechnology for Biofuels and Bioproducts, Issue 15, 2022, ISSN 2731-3654
Publisher: BioMed Central Ltd.
DOI: 10.1186/s13068-022-02107-z

Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase

Author(s): Beatriz Piniello; Javier Macías-León; Shun Miyazaki; Ana García-García; Ismael Compañón; Mattia Ghirardello; Víctor Taleb; Billy Veloz; Francisco Corzana; Atsushi Miyagawa; Carme Rovira; Ramon Hurtado-Guerrero
Published in: Nature Communications, Issue 14, 2023, Page(s) 5785, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-023-41238-1

From Mechanism-Based Retaining Glycosidase Inhibitors to Activity-Based Glycosidase Profiling

Author(s): Marta Artola, Johannes M. F. G. Aerts, Gijsbert A. van der Marel, Carme Rovira, Jeroen D. C. Codée, Gideon J. Davies, Herman S. Overkleeft
Published in: Journal of the American Chemical Society, Issue 146, 2024, Page(s) 24729-24741, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.4c08840

An Unusual His/Asp Dyad Operates Catalysis in Agar-Degrading Glycosidases

Author(s): Mert Sagiroglugil, Alba Nin-Hill, Elizabeth Ficko-Blean, Carme Rovira
Published in: ACS Catalysis, Issue 14, 2024, Page(s) 16897-16904, ISSN 2155-5435
Publisher: American Chemical Society
DOI: 10.1021/acscatal.4c04139

Conformational Free Energy Landscape of β-Glucose in the Gas Phase and Aqueous Solution: Energetic, Structural, and Electronic Changes

Author(s): Qinghua Liao, Mariana A. B. Morais, Carme Rovira, Alba Nin-Hill
Published in: ACS Omega, Issue 10, 2025, Page(s) 19903-19911, ISSN 2470-1343
Publisher: American Chemical Society (ACS)
DOI: 10.1021/acsomega.5c01543

Computer Simulation to Rationalize “Rational” Engineering of Glycoside Hydrolases and Glycosyltransferases

Author(s): Joan Coines, Irene Cuxart, David Teze, and Carme Rovira
Published in: The Journal of Physical Chemistry B, Issue 126 (4), 2022, Page(s) 802–812, ISSN 1520-6106
Publisher: American Chemical Society
DOI: 10.1021/acs.jpcb.1c09536

Rational tuning of the reactivity of three-memberet heterocycle ring openings via SN2 reactions

Author(s): T. Hansen, A. Nin-Hill, J. D. Codée, T. A. Hamlin, C. Rovira
Published in: Chemistry European Journal, Issue 28, 2022, ISSN 0947-6539
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/chem.202201649

Conformational and Electronic Variations in 1,2- and 1,5a-Cyclophellitols and their Impact on Retaining α-Glucosidase Inhibition

Author(s): Tim P. Ofman, Jurriaan J. A. Heming, Alba Nin-Hill, Florian Küllmer, Elisha Moran, Megan Bennett, Roy Steneker, Anne-Mei Klein, Gijs Ruijgrok, Ken Kok, Zach W. B. Armstrong, Johannes M. F. G. Aerts, Gijsbert A. Marel, Carme Rovira, Gideon J. Davies, Marta Artola, Jeroen D. C. Codée, Herman S. Overkleeft
Published in: Chemistry—A European Journal, Issue 30, 2024, Page(s) e202400723, ISSN 1521-3765
Publisher: Wiley-VCH GmbH
DOI: 10.1002/chem.202400723

Unraveling the molecular mechanism of polysaccharide lyases for efficient alginate degradation

Author(s): José Pablo Rivas-Fernández, Marlene Vuillemin, Bo Pilgaard, Leesa J. Klau, Folmer Fredslund, Charlotte Lund-Hanssen, Ditte H. Welner, Anne S. Meyer, J. Preben Morth, Flora Meilleur, Finn L. Aachmann, Carme Rovira, Casper Wilkens
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-025-56754-5

A Bioorthogonal Precision Tool for Human <i>N</i>-Acetylglucosaminyltransferase V

Author(s): Yu Liu, Ganka Bineva-Todd, Richard W. Meek, Laura Mazo, Beatriz Piniello, Olga Moroz, Sean A. Burnap, Nadima Begum, André Ohara, Chloe Roustan, Sara Tomita, Svend Kjaer, Karen Polizzi, Weston B. Struwe, Carme Rovira, Gideon J. Davies, Benjamin Schumann
Published in: Journal of the American Chemical Society, Issue 146, 2024, Page(s) 26707-26718, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.4c05955

A multiplexing activity-based protein profiling platform for dissection of a native bacterial xyloglucan-degrading system

Author(s): Nicholas McGregor ,Casper de Boer ,Quentin Foucart ,Thomas Beenakker ,Wendy Offen ,Jeroen Codee ,Lianne Willems ,Herman Overkleeft ,Gideon Davies
Published in: ACS Central Science, Issue 9, 12, 2023, Page(s) 2306–2314, ISSN 2374-7943
Publisher: American Chemical Society
DOI: 10.1021/acscentsci.3c00831

Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo

Author(s): Casper de Boer; Zachary Armstrong; Vincent A. J. Lit; Uri Barash; Gijs Ruijgrok; Ilanit Boyango; Merle M. Weitzenberg; Sybrin P. Schröder; Alexi J. C. Sarris; Nico J. Meeuwenoord; Pedro Bule; Yasmine Kayal; Neta Ilan; Jeroen D. C. Codée; Israel Vlodavsky; Herman S. Overkleeft; Gideon J. Davies; Liang Wu
Published in: Proceedings of the National Academy of Sciences, Issue 119, 31, 2022, Page(s) e2203167119, ISSN 1091-6490
Publisher: National Academy of Sciences
DOI: 10.1073/pnas.2203167119

Selective labelling of GBA2 in cells with fluorescent β-<scp>d</scp>-arabinofuranosyl cyclitol aziridines

Author(s): Qin Su, Max Louwerse, Rob F. Lammers, Elmer Maurits, Max Janssen, Rolf G. Boot, Valentina Borlandelli, Wendy A. Offen, Daniël Linzel, Sybrin P. Schröder, Gideon J. Davies, Herman S. Overkleeft, Marta Artola, Johannes M. F. G. Aerts
Published in: Chemical Science, Issue 15, 2024, Page(s) 15212-15220, ISSN 2041-6520
Publisher: Royal Society of Chemistry
DOI: 10.1039/d3sc06146a

Formation of a Covalent Adduct in Retaining β‐Kdo Glycosyl‐Transferase WbbB via Substrate‐Mediated Proton Relay

Author(s): Mert Sagiroglugil, Qinghua Liao, Antoni Planas, Carme Rovira
Published in: ChemCatChem, Issue 16, 2025, ISSN 1867-3880
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/cctc.202400769

<i>Epi</i>-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses

Author(s): Melissa Thaler, Tim P. Ofman, Ken Kok, Jurriaan J. A. Heming, Elisha Moran, Isabelle Pickles, Anouk A. Leijs, Adrianus M. C. H. van den Nieuwendijk, Richard J. B. H. N. van den Berg, Gijs Ruijgrok, Zachary Armstrong, Clarisse Salgado-Benvindo, Dennis K. Ninaber, Eric J. Snijder, Constant A. A. van Boeckel, Marta Artola, Gideon J. Davies, Herman S. Overkleeft, Martijn J. van Hemert
Published in: ACS Central Science, Issue 10, 2024, Page(s) 1594-1608, ISSN 2374-7943
Publisher: American Chemical Society (ACS)
DOI: 10.1021/acscentsci.4c00506

Enzymatic Hydrolysis of Human Milk Oligosaccharides. The Molecular Mechanism of Bifidobacterium Bifidum Lacto-N-biosidase

Author(s): Irene Cuxart, Joan Coines, Oriol Esquivias, Magda Faijes, Antoni Planas, Xevi Biarnés, and Carme Rovira
Published in: ACS Catalysis, Issue 12,8, 2022, Page(s) 4737-4743
Publisher: American Chemical Society
DOI: 10.1021/acscatal.2c00309

Synthesis of broad-specificity activity-based probes for exo-beta-mannosidases

Author(s): Nicholas G. S. McGregor; Chi-Lin Kuo; Thomas J. M. Beenakker; Chun-Sing Wong; Wendy A. Offen; Zachary Armstrong; Bogdan I. Florea; Jeroen D. C. Codée; Herman S. Overkleeft; Johannes M. F. G. Aerts; Gideon J. Davies
Published in: Organic & Biomolecular Chemistry, Issue 20, 2022, Page(s) 877-886, ISSN 1477-0520
Publisher: Royal Society of Chemistry
DOI: 10.1039/d1ob02287c

<i>Parascedosporium putredinis</i> NO1 tailors its secretome for different lignocellulosic substrates

Author(s): Conor J. R. Scott, Nicholas G. S. McGregor, Daniel R. Leadbeater, Nicola C. Oates, Janina Hoßbach, Amira Abood, Alexander Setchfield, Adam Dowle, Herman S. Overkleeft, Gideon J. Davies, Neil C. Bruce
Published in: Microbiology Spectrum, Issue 12, 2024, ISSN 2165-0497
Publisher: American Society for Microbiology
DOI: 10.1128/spectrum.03943-23

Molecular Basis for Inhibition of Heparanases and β‑Glucuronidasesby Siastatin B

Author(s): Yurong Chen, Adrianus M. C. H. van den Nieuwendijk, Liang Wu, Elisha Moran, Foteini Skoulikopoulou, Vera van Riet, Hermen S. Overkleeft, Gideon J. Davies and Zachary Armstrong
Published in: Journal of the American Chemical Society, Issue 146, 1, 2024, Page(s) 125-133, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.3c04162

Combinatorial assembly and design of enzymes

Author(s): R. Lipsh-Sokolik, O. Khersonsky, S. P. Schröder, C. de Boer, S.-Y. Hoch, G. J. Davies, H. S. Overkleeft and S. J. Fleishman
Published in: Science, Issue 379, 6628, 2023, Page(s) 195-201, ISSN 1095-9203
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.ade9434

The development of a broad-spectrum retaining β-exo-galactosidase activity-based probe

Author(s): Kuo, C.L.; Su, Q.; Nieuwendijk, A.M.C.H. van den; Beenakker, T.J.M.; Offen, W.A.; Willems, L.I.; Boot, R.G.; Sarris, A.J.C.; Rosa Alcalde Marques, A.R.A.; Codée, J.D.C.; Marel, G.A. van der; Florea, B.I.; Davies, G.J.; Overkleeft, H.S.; Aerts, J.M.F.G.
Published in: Organic & Biomolecular Chemistry, Issue 21, 2023, Page(s) 7813-7820, ISSN 1477-0520
Publisher: Royal Society of Chemistry
DOI: 10.1039/d3ob01261a

Xylose-Configured Cyclophellitols as Selective Inhibitors for Glucocerebrosidase

Author(s): Qin Su; Sybrin P. Schröder; Lindsey T. Lelieveld; Maria J. Ferraz; Marri Verhoek; Rolf G. Boot; Herman S. Overkleeft; Johannes M. F. G. Aerts; Marta Artola; Chi-Lin Kuo
Published in: Chembiochem, Issue 22 (21), 2021, Page(s) 3090-3098, ISSN 1439-4227
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.202100396

Evolution of Phosphorylase Activity in an Ancestral Glycosyltransferase

Author(s): Jorick Franceus, José Pablo Rivas-Fernández, Jolien Lormans, Carme Rovira and Tom Desmet
Published in: ACS Catalysis, Issue 14, 5, 2024, Page(s) 3103−3114, ISSN 2155-5435
Publisher: American Chemical Society
DOI: 10.1021/acscatal.3c05819

β-l- Arabino furano-cyclitol Aziridines Are Covalent Broad-Spectrum Inhibitors and Activity-Based Probes for Retaining β-l-Arabinofuranosidases

Author(s): Borlandelli V, Offen W, Moroz O, Nin-Hill A, McGregor N, Binkhorst L, Ishiwata A, Armstrong Z, Artola M, Rovira C, Davies GJ, Overkleeft HS.
Published in: ACS Chemical Biology, Issue 18 (12), 2023, Page(s) 2564–2573, ISSN 1554-8937
Publisher: American Chemical Society
DOI: 10.1021/acschembio.3c00558

Synthesis and Biological Evaluation of Deoxycyclophellitols as Human Retaining β‐Glucosidase Inhibitors

Author(s): Yevhenii Radchenko, Qin Su, Sybrin S. Schröder, Luke van Gijlswijk, Marta Artola, Johannes M. F. G. Aerts, Jeroen D. C. Codée, Herman S. Overkleeft
Published in: Chemistry – A European Journal, Issue 30, 2024, ISSN 0947-6539
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/chem.202402988

Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases

Author(s): Daniël van der Gracht; Rhianna J. Rowland; Véronique Roig-Zamboni; Maria J. Ferraz; Max Louwerse; Paul P. Geurink; Johannes M. F. G. Aerts; Gerlind Sulzenbacher; Gideon J. Davies; Herman S. Overkleeft; Marta Artola
Published in: Chemical Science, Issue 14, 2023, Page(s) 9136–9144, ISSN 2041-6539
Publisher: Royal Society of Chemistry
DOI: 10.1039/d3sc01021j

In silico modelling of the function of disease-related CAZymes

Author(s): Alba Nin-Hill, Beatriz Piniello, Carme Rovira
Published in: Essays in Biochemistry, Issue 67 (3), 2023, Page(s) 355–372, ISSN 0071-1365
Publisher: Portland Press, Ltd.
DOI: 10.1042/ebc20220218

Detection of Sulfoquinovosidase Activity in Cell Lysates Using Activity‐Based Probes

Author(s): Zirui Li, Isabelle B. Pickles, Mahima Sharma, Benjamin Melling, Luise Pallasdies, Jeroen D. C. Codée, Spencer J. Williams, Herman S. Overkleeft, Gideon J. Davies
Published in: Angewandte Chemie International Edition, Issue 63, 2024, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.202401358

1,6-epi-Cyclophellitol cyclosulfamidate is a bona fide lysosomal α-glucosidase stabilizer for the treatment of Pompe disease

Author(s): Ken Kok; Chi-Lin Kuo; Rebecca E. Katzy; Lindsey T. Lelieveld; Liang Wu; Véronique Roig-Zamboni; Gijsbert A. van der Marel; Jeroen D. C. Codée; Gerlind Sulzenbacher; Gideon J. Davies; Herman S. Overkleeft; Johannes M. F. G. Aerts; Marta Artola
Published in: Journal of the American Chemical Society, Issue 144, 2022, Page(s) 14819-14827, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.2c05666

4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors

Author(s): V. Borlandelli, Z. Armstrong, A. Nin-Hill, J. Codée, Ll. Raich, M. Artola, C. Rovira, G. Davies, H. S. Overkleeft
Published in: ChemMedChem, 2022, ISSN 1860-7179
Publisher: Wiley - V C H Verlag GmbbH & Co.
DOI: 10.1002/cmdc.202200580

Glycosidase mechanisms: Sugar conformations and reactivity in endo- and exo-acting enzymes

Author(s): Mariana Abrahão Bueno Morais, Alba Nin-Hill, Carme Rovira
Published in: Current Opinion in Chemical Biology, Issue 74, 2023, Page(s) 102282, ISSN 1879-0402
Publisher: Elsevier B.V.
DOI: 10.1016/j.cbpa.2023.102282

Intellectual Property Rights

Patent (2)

PSEUDO-DISACCHARIDE COMPOUNDS

Application/Publication number: 20 23050231
Date: 2023-04-28
Applicant(s): UNIVERSITY OF YORK

PSEUDO-DISACCHARIDE COMPOUNDS

Application/Publication number: 20 23050231
Date: 2023-04-28
Applicant(s): UNIVERSITEIT LEIDEN