Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(10), P. 1101 - 1113

Published: Aug. 15, 2023

Abstract The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous exogenous insults. Disruption these safeguard homeostatic mechanisms can lead to unpredictable inflammatory autoimmune responses, whereas deficiency pathways may orchestrate immunosuppressive programs contribute perpetuate chronic infections, but also influence cancer development progression. Glycans have emerged as essential components circuits, acting fine-tuners immunological potential molecular targets for manipulation tolerance activation in a wide range pathologic settings. Cell surface glycans, present cells, tissues the extracellular matrix, been proposed serve “self-associated patterns” store structurally relevant biological data. responsibility deciphering this information relies on different families glycan-binding proteins (including galectins, siglecs C-type lectins) which, upon recognition specific carbohydrate structures, recalibrate magnitude, nature fate responses. This process tightly regulated diversity glycan structures establishment multivalent interactions cell receptors matrix. Here we review spatiotemporal regulation selected glycan-modifying processes including mannosylation, complex N -glycan branching, core 2 O elongation, LacNAc extension, well terminal sialylation fucosylation. Moreover, illustrate examples highlight contribution control their integration with canonical tolerogenic pathways. Finally, discuss power glycans source immunomodulatory signals could be leveraged treatment inflammation infection.

Language: Английский

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Dissecting the Conformational Stability of a Glycan Hairpin

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(9), P. 6369 - 6376

Published: Feb. 20, 2024

Systematic structural studies of model oligopeptides revealed important aspects protein folding and offered design principles to access non-natural materials. In the same way, rules that regulate glycan could be established by studying synthetic oligosaccharide models. However, their analysis is often limited due analytical complexity. By utilizing a capable spontaneously into hairpin conformation as system, we investigated factors contribute its conformational stability in aqueous solution. The modular featured trisaccharide turn unit two β-1,4-oligoglucoside stacking strands allowed for systematic chemical modifications sequence, including introduction NMR labels staples. Nuclear magnetic resonance assisted molecular dynamics simulations stereoelectronic effects multiple glycan–glycan interactions are major determinants stabilization. Chemical primary sequence (e.g., strand elongation) can employed fine-tune rigidity motifs distant from modification sites. These results inspire other architectures, with implications glycobiology material sciences.

Language: Английский

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Speeding-up the Determination of Protein–Ligand Affinities by STD NMR: The Reduced Data Set STD NMR Approach (rd-STD NMR)

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(2), P. 615 - 619

Published: Jan. 2, 2024

STD NMR spectroscopy is a powerful ligand-observed tool for screening and characterizing the interactions of small molecules low molecular weight fragments with given macromolecule, identifying main intermolecular contacts in bound state. It also analytical technique accurate determination protein–ligand dissociation constants (KD) medium-to-weak affinity, interest pharmaceutical industry. However, KD epitope mapping requires long series experiments at increasing saturation times to carry out full analysis using so-called build-up curve approach apply "initial slopes approximation". Here, we have developed new protocol bypass this important limitation, which allows us obtain initial by just two and, hence, very quickly determine precise NMR.

Language: Английский

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Invasive plant-derived biochar for sustainable bioremediation of pesticide contaminated soil

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 481, P. 148689 - 148689

Published: Jan. 11, 2024

Language: Английский

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Quantifying Siglec-sialylated ligand interactions: a versatile ¹⁹F-T₂ CPMG filtered competitive NMR displacement assay

Chemical Science, Journal Year: 2024, Volume and Issue: 15(27), P. 10612 - 10624

Published: Jan. 1, 2024

Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are integral cell surface proteins crucial for the regulation of immune responses and maintenance tolerance through interactions with sialic acids.

Language: Английский

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Nuclear magnetic resonance revealed the structural unit difference and polymerization process of pre-humic acid from different organic waste sources

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140457 - 140457

Published: Feb. 1, 2025

Language: Английский

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ProtCB-Bind: Protein-carbohydrate binding site prediction using an ensemble of classifiers

Carbohydrate Research, Journal Year: 2025, Volume and Issue: 552, P. 109453 - 109453

Published: March 5, 2025

Language: Английский

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Structural characterization and physicochemical properties of wine and yeast mannans and evaluation of their interactions with catechin and epicatechin

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 306, P. 141798 - 141798

Published: March 5, 2025

Language: Английский

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Investigation of N-Glycan Functions in Receptor for Advanced Glycation End Products V Domain through Chemical Glycoprotein Synthesis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18270 - 18280

Published: June 25, 2024

The receptor for advanced glycation end products (RAGE) plays a crucial role in inflammation-related pathways and various chronic diseases. Despite the recognized significance of N-glycosylation ligand-binding V domain (VD) RAGE, comprehensive understanding site-activity structure-activity relationships is lacking due to challenges obtaining homogeneous glycoprotein samples through biological expression. Here, we combined chemical chemoenzymatic approaches synthesize RAGE-VD its congeners with Asn3-glycosylation by incorporating precise N-glycan structures. Evaluation these revealed that, comparison other forms, α2,6-sialylated at Asn3 site results more potent inhibition HMGB1-induced nuclear factor-κB (NF-κB) expression RAGE-overexpressing cells. Hydrogen/deuterium exchange-mass spectrum analysis sialylated RAGE-VD-induced interaction region within HMGB1. Conversely, VD has negligible effects on RAGE-VD/S100B interactions. This study established an approach accessing homogeneously glycosylated explored modulatory interactions between ligand proteins.

Language: Английский

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Clustering Zwitterionic Amino Acids at the Upper Rim of Cone Calix[4]arene Triggers the Selective Recognition of Gram‐Negative Bacterial Envelope

Small Structures, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Eleven calix[4]arene ligands, bearing zwitterionic α‐amino acids or charged ammonium sulfonate/carboxylate groups, are synthesized and screened for the binding to envelopes of three bacterial strain representatives Gram‐positive, Gram‐negative, mycobacteria. The is followed by on‐cell Saturation Transfer Difference Nuclear Magnetic Resonance (NMR) experiments directly on alive cells. While anionic tetrasulfonatocalixarene does not bind any strains significantly cationic calixarenes strongly both Gram‐positive Gram‐negative bacteria, tetraprolino‐ tetraphenylalaninocalix[4]arene show a remarkable selectivity Gram‐negatives over Gram‐positives tetraprolinocalixarene binds lipopolysaccharides extracted from two bacteria ( Pseudomonas putida Escherichia coli ), suggesting these biomacromolecules as possible targets in recognition their cell walls. ligand epitope map demonstrates deep involvement amino calixarene aromatic nuclei interaction. In this study, first time, ability synthetic macrocycles selectively recognize envelope highlighted, way chemical modifications structure paved develop devices detection treatment infections, thus allowing add another string bow fight against antimicrobial resistance.

Language: Английский

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