Multivalent glycan arrays

Mende, Marco; Bordoni, Vittorio; Tsouka, Alexandra; Loeffler, Felix F.; Delbianco, Martina; Seeberger, Peter H.

doi:10.1039/c9fd00080a

Cited by 26 publications

(25 citation statements)

References 196 publications

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“…Considering the broad structural diversity of glycoconjugates, techniques enabling the parallel and quantitative analysis of a wide range of carbohydrate structures are likely to yield the most reliable information about the specificity and affinity of antibodies recognizing glycan antigens. Accordingly, large-scale glycan arrays have turned out as being valuable resources for the quantitative analysis of carbohydrate-protein interactions [199].…”

Section: Analytical Toolsmentioning

confidence: 99%

Emergence and significance of carbohydrate-specific antibodies

Kappler

Hennet

2020

Genes Immun

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Carbohydrate-specific antibodies are widespread among all classes of immunoglobulins. Despite their broad occurrence, little is known about their formation and biological significance. Carbohydrate-specific antibodies are often classified as natural antibodies under the assumption that they arise without prior exposure to exogenous antigens. On the other hand, various carbohydrate-specific antibodies, including antibodies to ABO blood group antigens, emerge after the contact of immune cells with the intestinal microbiota, which expresses a vast diversity of carbohydrate antigens. Here we explore the development of carbohydrate-specific antibodies in humans, addressing the definition of natural antibodies and the production of carbohydrate-specific antibodies upon antigen stimulation. We focus on the significance of the intestinal microbiota in shaping carbohydrate-specific antibodies not just in the gut, but also in the blood circulation. The structural similarity between bacterial carbohydrate antigens and surface glycoconjugates of protists, fungi and animals leads to the production of carbohydrate-specific antibodies protective against a broad range of pathogens. Mimicry between bacterial and human glycoconjugates, however, can also lead to the generation of carbohydrate-specific antibodies that cross-react with human antigens, thereby contributing to the development of autoimmune disorders.

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Section: Analytical Toolsmentioning

confidence: 99%

Emergence and significance of carbohydrate-specific antibodies

Kappler

Hennet

2020

Genes Immun

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“…In the natural state, the glycan-GBP interaction often occurs in a multivalent fashion, accomplished by clustered presentation of ligands and/or carbohydrate recognition domains. Many labs have, thus, developed natural protein or synthetic polymers to generate glycan microarrays (Maierhofer et al, 2007;Jayaraman, 2009;Huang et al, 2015;Mende et al, 2019). It would be beneficial to have easily accessible and facile technologies to generate linker-bearing scaffolds to achieve higher binding avidity in the future.…”

Section: Future Directions In Linker Developmentmentioning

confidence: 99%

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

et al. 2019

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Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool. A variety of methods have been developed to better present the glycans so that they mimic natural presentations. Breakthroughs in chemical biology approaches have also made available glycans with sophisticated structures that were considered practically impossible just a few decade ago. Glycan microarrays provide a wealth of valuable information in immunological studies. They allow for discovery of detailed glycan binding preferences or novel binding epitopes of known endogenous immune receptors, which can potentially lead to the discovery of natural ligands that carry the glycans. Glycan microarrays also serve as a platform to discover new GBPs that are vital to the process of infection and invasion by microorganisms. This review summarizes the construction strategies and the immunological applications of glycan microarrays, particularly focused on those with the most comprehensive sets of glycan structures. We also review new methods and technologies that have evolved. We believe that glycan microarrays will continue to benefit the growing research community with various interests in the field of immunology.

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“…However, structural conformations of glycans are not easy to determine due to their intrinsic mobility and the scarce capability of some structural techniques, like X‐ray diffraction, to solve their conformations (Fadda and Woods, 2010; Gimeno et al ., 2020). Moreover, protein–glycan interactions are weak, with affinities ranging from the µ m to the m m range, due to the formation of transient structural states that result in more dynamic interactions than protein–peptide ones (Otto et al ., 2011; Sapay et al ., 2013; Isaacson and Díaz‐Moreno, 2019; Mende et al ., 2019; Gimeno et al ., 2020; Haab and Klamer, 2020). In silico approaches, particularly molecular dynamics, can aid to solve complex protein–glycan interactions, but simulation of carbohydrate‐based structures can also be challenging since the initial protein–glycan conformation and the force field employed during the simulation might be critical steps to obtain reliable results.…”

Section: Introductionmentioning

confidence: 99%

Computational prediction method to decipher receptor–glycoligand interactions in plant immunity

et al. 2021

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Microbial and plant cell walls have been selected by the plant immune system as a source of microbe-and plant damage-associated molecular patterns (MAMPs/DAMPs) that are perceived by extracellular ectodomains (ECDs) of plant pattern recognition receptors (PRRs) triggering immune responses. From the vast number of ligands that PRRs can bind, those composed of carbohydrate moieties are poorly studied, and only a handful of PRR/glycan pairs have been determined. Here we present a computational screening method, based on the first step of molecular dynamics simulation, that is able to predict putative ECD-PRR/ glycan interactions. This method has been developed and optimized with Arabidopsis LysM-PRR members CERK1 and LYK4, which are involved in the perception of fungal MAMPs, chitohexaose (1,4-b-D-(GlcNAc) 6) and laminarihexaose (1,3-b-D-(Glc) 6). Our in silico results predicted CERK1 interactions with 1,4-b-D-(GlcNAc) 6 whilst discarding its direct binding by LYK4. In contrast, no direct interaction between CERK1/laminarihexaose was predicted by the model despite CERK1 being required for laminarihexaose immune activation, suggesting that CERK1 may act as a co-receptor for its recognition. These in silico results were validated by isothermal titration calorimetry binding assays between these MAMPs and recombinant ECDs-LysM-PRRs. The robustness of the developed computational screening method was further validated by predicting that CERK1 does not bind the DAMP 1,4-b-D-(Glc) 6 (cellohexaose), and then probing that immune responses triggered by this DAMP were not impaired in the Arabidopsis cerk1 mutant. The computational predictive glycan/PRR binding method developed here might accelerate the discovery of protein-glycan interactions and provide information on immune responses activated by glycoligands.

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Multivalent glycan arrays

Abstract: In this introductory lecture we discuss the state-of-the-art glycan microarray technology, with emphasis on novel approaches to immobilize collections of glycans in a defined, multivalent manner.

Cited by 26 publications

References 196 publications

Emergence and significance of carbohydrate-specific antibodies

Emergence and significance of carbohydrate-specific antibodies

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

Computational prediction method to decipher receptor–glycoligand interactions in plant immunity

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