Exploring multivalent carbohydrate-protein interactions by NMR
Nuclear Magnetic Resonance (NMR) has been widely employed to assess diverse features of glycan-protein molecular recognition events. Different types of qualitative and quantitative information at different degrees of resolution and complexity can be extracted from the proper application of the avail...
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| Published in | Chemical Society reviews Vol. 52; no. 5; pp. 1591 - 1613 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
06.03.2023
The Royal Society of Chemistry |
| Subjects | |
| Online Access | Get full text |
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| Summary: | Nuclear Magnetic Resonance (NMR) has been widely employed to assess diverse features of glycan-protein molecular recognition events. Different types of qualitative and quantitative information at different degrees of resolution and complexity can be extracted from the proper application of the available NMR-techniques. In fact, affinity, structural, kinetic, conformational, and dynamic characteristics of the binding process are available. Nevertheless, except in particular cases, the affinity of lectin-sugar interactions is weak, mostly at the low mM range. This feature is overcome in biological processes by using multivalency, thus augmenting the strength of the binding. However, the application of NMR methods to monitor multivalent lectin-glycan interactions is intrinsically challenging. It is well known that when large macromolecular complexes are formed, the NMR signals disappear from the NMR spectrum, due to the existence of fast transverse relaxation, related to the large size and exchange features. Indeed, at the heart of the molecular recognition event, the associated free-bound chemical exchange process for both partners takes place in a particular timescale. Thus, these factors have to be considered and overcome. In this review article, we have distinguished, in a subjective manner, the existence of multivalent presentations in the glycan or in the lectin. From the glycan perspective, we have also considered whether multiple epitopes of a given ligand are presented in the same linear chain of a saccharide (
i.e.
, poly-LacNAc oligosaccharides) or decorating different arms of a multiantennae scaffold, either natural (as in multiantennae
N
-glycans) or synthetic (of dendrimer or polymer nature). From the lectin perspective, the presence of an individual binding site at every monomer of a multimeric lectin may also have key consequences for the binding event at different levels of complexity.
Nuclear Magnetic Resonance (NMR) has been widely employed to assess diverse features of glycan-protein molecular recognition events. |
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| Bibliography: | Unai Atxabal studied Biochemistry at the University of the Basque Country (Spain) and completed a MSc in Medicinal Chemistry focusing in drug development and organic synthesis at the University of Copenhagen (Denmark). He is currently working on his PhD within the Marie-Sk odowska-Curie Innovative Training Network "BactiVax" under the supervision of Prof. Jesús Jiménez-Barbero and Dr June Ereño-Orbea. The PhD project is focused on studying molecular recognition processes of antigens by key receptors using state-of-the-art NMR techniques combined with molecular dynamics and other biophysical techniques. The goal is to understand these processes to design and synthesize novel drug-like compounds. Jesús Jiménez-Barbero is Ikerbasque Research Professor and Scientific Director of CIC bioGUNE since 2014. He received his PhD in 1987 at Madrid. After postdoctoral stays at Zürich, Mill Hill, and Pittsburgh, he returned to Madrid (CSIC) and started to work on protein-carbohydrate interactions. In 2002 he was promoted to CSIC Research Professor at CIB-CSIC, where he developed his scientific activity until he moved to Bilbao. His scientific interest is focused in the field of molecular recognition and Chemical Glycobiology, employing a multidisciplinary approach that combines synthesis, biochemistry, molecular biology, molecular modeling, and especially NMR, enjoying a wide network of scientific collaborations worldwide. Jon I. Quintana studied chemistry at the University of the Basque Country. In 2017, he joined the chemical glycobiology lab at CIC bioGUNE, where he employed different NMR techniques to characterize the binding of a monoclonal antibody to different oligosaccharides. In 2018, he started his PhD under the supervision of Prof. Jesús Jiménez-Barbero and Dr Ana Ardá, studying molecular recognition events between lectins and sugar by means of NMR, ITC, and MD simulations. In 2021, he performed a secondment with Dr Martina Delbianco (MPIKI, Potsdam), where he worked on the synthesis of glycans using a solid phase synthesizer. He obtained his PhD in 2022 and his research focuses on understanding host-pathogen interactions mediated through glycans. Ana Ardá studied Chemistry at the University of A Coruña, from where she received her doctorate in Chemistry in 2006. Between 2006 and 2008 she carried out a postdoctoral stay in at Utrecht University, with Prof. Hans Kamerling where she started to work with carbohydrates. In 2008 she moved to Centro de Investigaciones Biológicas (CIB-CSIC) in Madrid to join Prof. Jiménez-Barbero's group. In 2014 she moved to CIC bioGUNE where she is Ikerbasque Research Associate and Associated Principal Investigator. Her research interests are focused on the study of glycan-protein interactions through a multidisciplinary approach, with a special focus on NMR techniques. Luca Unione studied Chemistry at the University of Napoli Federico II (Italy). He received the PhD in 2016 in Madrid (Spain), in the framework of a ITN-Marie Sk odowska-Curie Action, working in the field of structural characterization of carbohydrates, glycomimetics, and their interactions with glycan binding proteins. After carrying out a postdoctoral stay in the company Atlas molecular Pharma in Biscay (Spain, he moved to Utrecht University (The Netherlands) as postdoctoral fellow (2019-2021) under the International Human Frontier Science Program (HFSP). Since 2022 he is Ikerbasque Research Fellow (tenure track) at CIC bioGUNE. His research interest is focused on the understanding of the role of glycans as regulators in biomedical processes, with a special focus on chemo-enzymatic synthesis of glycans and the study of glycan-protein interactions through a multidisciplinary approach. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 Equal contribution. |
| ISSN: | 0306-0012 1460-4744 1460-4744 |
| DOI: | 10.1039/d2cs00983h |