Carbohydrate-carbohydrate Interactions Research Articles

Self-Assembly of Glycolipid Epimers: Their Supramolecular Morphology Control and Immunoactivation Function.

Although advances have been made in carbohydrate-based macromolecular self-assembly, harnessing epimers of carbohydrates to perform molecular assembly and further investigating the properties of supramolecular materials remain little explored. Herein, two classes of stereoisomeric glycolipid amphiphiles based on d-N-acetylgalactosamine (GalNAc) are reported, and they can aggregate into ribbon-like structures in the aqueous solution due to amphiphilic property, which allow to obtain glycocalyx-mimicking supramolecular materials. The subtle distinction in glycoside configuration of GalNAc-α-SSA and GalNAc-β-SSA dictates the different molecular packing in self-assembled structures. Since driven by the distinguishing carbohydrate-carbohydrate interactions, the ribbon-like architectures transform into spherical nanostructures via mixing GalNAc-α-SSA and GalNAc-β-SSA. The resulting spherical micelles fabricated by blending glycolipid epimers can potentiate the macrophage- and dendritic cell-mediated immune responses in vitro. Such glycolipid epimers will pave the way to create glycocalyx-mimicking immune modulators by incorporating stereochemistry into supramolecular self-assembly.

Measuring pico-Newton Forces with Lipid Anchors as Force Sensors in Molecular Dynamics Simulations.

Binding forces between biomolecules are ubiquitous in nature but sometimes as weak as a few pico-Newtons (pN). In many cases, the binding partners are attached to biomembranes with the help of a lipid anchor. One important example are glycolipids that promote membrane adhesion through weak carbohydrate-carbohydrate binding between adjacent membranes. Here, we use molecular dynamics (MD) simulations to quantify the forces generated by bonds involving membrane-anchored molecules. We introduce a method in which the protrusion of the lipid anchors from the membrane acts as the force sensor. Our results with two different glycolipids reveal binding forces of up to 20 pN and corroborate the recent notion that carbohydrate-carbohydrate interactions are generic rather than specific.

Antibodies to Glycolipids in Guillain-Barré Syndrome, Miller Fisher Syndrome and Related Autoimmune Neurological Diseases.

Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are acute immune-mediated neuropathies, often preceded by an infection. Anti-glycolipid antibodies are frequently detected in patients' sera in the acute-phase. In particular, IgG anti-GQ1b antibodies are positive in as high as 90% of MFS cases. Anti-glycolipid antibodies are useful for the diagnosis of GBS and MFS. In addition, those antibodies may be directly involved in the pathogenetic mechanisms by binding specifically to the regions where the target glycolipid antigen is densely localized. This was proven by the development of animal models of anti-glycolipid antibody-mediated neuropathies. The presence of antibodies that specifically recognize a new conformational epitope formed by two gangliosides (ganglioside complex) in the acute-phase sera of some GBS patients suggested existence of a carbohydrate-carbohydrate interaction between glycolipids. Further intensive research is needed to clarify this point.

Multifaceted Computational Modeling in Glycoscience

Glycoscience assembles all the scientific disciplines involved in studying various molecules and macromolecules containing carbohydrates and complex glycans. Such an ensemble involves one of the most extensive sets of molecules in quantity and occurrence since they occur in all microorganisms and higher organisms. Once the compositions and sequences of these molecules are established, the determination of their three-dimensional structural and dynamical features is a step toward understanding the molecular basis underlying their properties and functions. The range of the relevant computational methods capable of addressing such issues is anchored by the specificity of stereoelectronic effects from quantum chemistry to mesoscale modeling throughout molecular dynamics and mechanics and coarse-grained and docking calculations. The Review leads the reader through the detailed presentations of the applications of computational modeling. The illustrations cover carbohydrate-carbohydrate interactions, glycolipids, and N- and O-linked glycans, emphasizing their role in SARS-CoV-2. The presentation continues with the structure of polysaccharides in solution and solid-state and lipopolysaccharides in membranes. The full range of protein-carbohydrate interactions is presented, as exemplified by carbohydrate-active enzymes, transporters, lectins, antibodies, and glycosaminoglycan binding proteins. A final section features a list of 150 tools and databases to help address the many issues of structural glycobioinformatics.

Examination of the Relationship between the ABO Blood Group and Susceptibility to SARS-CoV-2 Infection Risk

The ABO blood group system has been linked with multiple infectious and non-infectious diseases and disorders such as, hepatitis B, dengue haemorrhagic fever, cancer, cardiovascular diseases, hematologic disorders, metabolic diseases, malaria, etc. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the virus that causes COVID-19 (Coronavirus disease 2019), a respiratory infectious disease that has become a global pandemic. Several reports have investigated the role of ABO blood groups in susceptibility/resistance to various infectious Diseases, and have proposed that ABO blood group polymorphism may be linked with COVID-19 susceptibility and clinical outcomes, however, the results were questionable. It has been suggested that blood type O may have a protective role against COVID-19 infection, as blood group O individuals were found COVID-19 positive in lower levels. This could emonstrate that those Individuals are less susceptible to infection, or are asymptomatic in higher proportions, or may be associated with a slightly lower risk for severe COVID-19 disease. It has been hypothesized that the mentioned association can be probably explained by the configuration of distribution of the sialic acid-containing receptors on host cell surfaces induced by ABO antigens through carbohydrate-carbohydrate interactions, that could maximize or minimize the SARS-CoV-2 virus spike protein (S) binding to the host cell. The classical viral entry through the ACE-2 receptors can be prevented by the anti-A antibodies that are produced from O and B blood group individuals. Experimental models based on cellular lines suggested a possible explanation for blood type configuration of infection showing that S protein/ACE-2-dependent adhesion to ACE 2-expressing cells was especially inhibited by natural or monoclonal human anti-A antibodies. Consequently, non-A blood groups individuals, mainly O, or B blood group, that produce anti-A antibodies, may have a lesser degree of susceptible to SARS-CoV-2 infection due to the inhibitory effects of anti-A antibodies. Therefore, it is possible that individuals with group A are more susceptible to SARS-CoV-2 infection and/or manifestation of a severe status.

Sensitive chemoselectivity of cellulose nanocrystal films

Cellulose nanocrystals (CNCs), self-assembled into a chiral nematic structure film, create an advanced platform for the fabrication of remarkable sensing, photonic and chiral nematic materials. Despite extensive progress in the knowledge of functions of CNCs, their chemoselectivity has rarely been reported. Here, we report a brand-new perspective of CNCs in chemoselectivity, which shows sensitive selectivity even between isomers of monosaccharides and disaccharides by generating discernible crystal patterns. This sensitive selectivity of glucose homologs is attributed to the selective carbohydrate–carbohydrate interactions (CCIs) through generating hydrogen bonds between CNC units and the glucose homologs, endowing a remarkable color variation of the CNC films. Moreover, the CCIs are distinct for different immersion times and concentrations of glucose homologs, verified through Fourier Transform Infrared Spectroscopy (FTIR) spectra. Based on the sensitive CCIs, pristine CNC films are then used as templates to generate chiral mesoporous carbon films with tunable specific surface areas by assembly of CNC suspensions and the glucose homologs. We envision that the sensitive chemoselectivity of CNC films as well as precise structure modulation could provide insights into the recognition of carbohydrates and the preparation of mesoporous carbon in numerous practical applications. A pristine chiral nematic cellulose nanocrystal film with sensitive chemoselectivity to glucose homologues and even isomers of monosaccharides and disaccharide are prepared through self-assembly. For different kinds of glucose homologs, distinct crystal morphologies are formed due to the selective carbohydrate–carbohydrate interactions. Besides, the highly ordered left-helical layered structure of pristine cellulose nanocrystal film could be used as templates for the precise construction of delicate nanostructures.

Lactosylceramide-enriched microdomains mediate human neutrophil immunological functions via carbohydrate-carbohydrate interaction

The innate immune system of mammalian cells is the first line of defense against pathogenic microorganisms. Phagocytes, which play the central role in this system, engulf microorganisms by a mechanism that involves pattern recognition receptors on their own surface and pathogen-associated molecular patterns (PAMPs) expressed by the microorganism. Components of PAMPs include glycans (polysaccharides) and glycoconjugates (carbohydrates covalently linked to other biological molecules). Pathogenic microorganisms display specific binding affinity to various types of glycosphingolipids (sphingosine-containing glycolipids; GSLs), and GSLs are involved in host-pathogen interactions. We observed that lactosylceramide (LacCer), a neutral GSL, binds directly to certain pathogen-specific molecules (e.g., Candida albicans-derived β-glucans, mycobacterial lipoarabinomannan) via carbohydrate-carbohydrate interaction. LacCer is expressed highly on human neutrophils, and forms membrane microdomains. Such LacCer-enriched microdomains mediate several important neutrophil functions, including chemotaxis, phagocytosis, and superoxide generation. Human neutrophils phagocytose pathogenic mycobacteria (including Mycobacterium tuberculosis) through carbohydrate-carbohydrate interaction between LacCer on their own surface and mannose-capped lipoarabinomannan on the bacterium. During recognition of pathogen-specific glycans, direct association of LacCer-containing C24 fatty acid chain with Lyn (a Src family kinase) is necessary for signal transduction from the neutrophil exterior to interior. Pathogenic mycobacteria utilize a similar interaction to avoid killing by neutrophils. We describe here the mechanisms whereby LacCer mediates neutrophil immune systems via carbohydrate-carbohydrate interaction.

Experimental and computational characterization of dynamic biomolecular interaction systems involving glycolipid glycans.

On cell surfaces, carbohydrate chains that modify proteins and lipids mediate various biological functions, which are exerted not only through carbohydrate-protein interactions but also through carbohydrate-carbohydrate interactions. These glycans exhibit considerable degrees of conformational variability and often form clusters providing multiple binding sites. The integration of nuclear magnetic resonance spectroscopy and molecular dynamics simulation has made it possible to delineate the dynamical structures of carbohydrate chains. This approach has facilitated the remodeling of oligosaccharide conformational space in the prebound state to improve protein-binding affinity and has been applied to visualize dynamic carbohydrate-carbohydrate interactions that control glycoprotein-glycoprotein complex formation. Functional glycoclusters have been characterized by experimental and computational approaches applied to various model membranes and artificial self-assembling systems. This line of investigation has provided dynamic views of molecular assembling on glycoclusters, giving mechanistic insights into physiological and pathological molecular events on cell surfaces as well as clues for the design and creation of molecular systems exerting improved glycofunctions. Further development and accumulation of such studies will allow detailed understanding and artificial control of the "glycosynapse" foreseen by Dr. Sen-itiroh Hakomori.

Carbohydrate-carbohydrate interaction drives the preferential insertion of dirhamnolipid into glycosphingolipid enriched membranes

Rhamnolipids (RLs) are among the most important biosurfactants produced by microorganisms, and have been widely investigated because of their multiple biological activities. Their action appears to depend on their structural interference with lipid membranes, therefore several studies have been performed to investigate this aspect. We studied by X-ray scattering, neutron reflectometry and molecular dynamic simulations the insertion of dirhamnolipid (diRL), the most abundant RL, in model cellular membranes made of phospholipids and glycosphingolipids. In our model systems the affinity of diRL to the membrane is highly promoted by the presence of the glycosphingolipids and molecular dynamics simulations unveil that this evidence is related to sugar-sugar attractive interactions at the membrane surface. Our results improve the understanding of the plethora of activities associated with RLs, also opening new perspectives in their selective use for pharmaceutical and cosmetics formulations. Additionally, they shed light on the still debated role of carbohydrate-carbohydrate interactions as driving force for molecular contacts at membrane surface.

Development of a pulse-induced electrochemical biosensor based on gluconamide for Gram-negative bacteria detection.

Pathogenic bacteria can cause the outbreaks of disease and threaten human health, which stimulates the development of advanced detection techniques. Herein, a specific and sensitive electrochemical biosensor for Gram-negative bacteria was established based on the conductive polymer with artificial muscle properties. Theeffective recognition was achieved through the specific carbohydrate-carbohydrate interaction between gluconamide and lipopolysaccharide. Theapplication of impulse voltage enhances the efficiency of recognition and shortens the detection time through the temporary deformation of the electrode surface, with a limit of detection (LOD) of1 × 100CFU/mL anda linear range of 1 × 100 - 1 × 106CFU/mL for Escherichia coli (E. coli). In addition tothe merits of low cost, high efficiency, and rapidity, the developedlabel-free electrochemical biosensor can also be applicable for other Gram-negative bacteria, owning promising potential in the application of portable devices and paving a potential way for the construction of electrochemical biosensors.

A brief insight to the role of glyconanotechnology in modern day diagnostics and therapeutics

Carbohydrate-protein and carbohydrate-carbohydrate interactions are very important for various biological processes. Although the magnitude of these interactions is low compared to that of protein-protein interaction, the magnitude can be boosted by multivalent approach known as glycocluster effect. Nanoparticle platform is one of the best ways to present diverse glycoforms in multivalent manner and thus, the field of glyconanotechnology has emerged as an important field of research considering their potential applications in diagnostics and therapeutics. Considerable advances in the field have been achieved through development of novel techniques, use of diverse metallic and non-metallic cores for better efficacy and application of ever-increasing number of carbohydrate ligands for site-specific interaction. The present review encompasses the recent developments in the area of glyconanotechnology and their future promise as diagnostic and therapeutic tools.

Hamiltonian Replica Exchange with Solute Tempering and Biasing Potentials (HREST-BP): Applications in Antibody Glycoengineering

The glycosylation of biomolecules is essential for cell recognition and immune regulation. Intermolecular carbohydrate-carbohydrate interactions between the antibody Fc fragment and Fc receptor (FcR) are required for immune-cell activation. Further, antibody Fc glycans can be glycoengineered to enhance these interactions for applications in cancer immunotherapy: e.g. the removal of core fucose in the antibody Fc glycan enhances binding of the Fc fragment to the FcR and, thereby, immune-cell activity.

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

The influence of ABO blood groups on COVID-19 susceptibility and severity: A molecular hypothesis based on carbohydrate-carbohydrate interactions

The world is experiencing one of the most difficult moments in history with the COVID-19 pandemic, a disease caused by SARS-CoV-2, a new type of coronavirus. Virus infectivity is mediated by the binding of Spike transmembrane glycoprotein to specific protein receptors present on cell host surface. Spike is a homotrimer that emerges from the virion, each monomer containing two subunits named S1 and S2, which are related to cell recognition and membrane fusion, respectively. S1 is subdivided in domains S1A (or NTD) and S1B (or RBD), with experimental and in silico studies suggesting that the former binds to sialic acid-containing glycoproteins, such as CD147, whereas the latter binds to ACE2 receptor. Recent findings indicate that the ABO blood system modulates susceptibility and progression of infection, with type-A individuals being more susceptible to infection and/or manifestation of a severe condition. Seeking to understand the molecular mechanisms underlying this susceptibility, we carried out an extensive bibliographic survey on the subject. Based on this survey, we hypothesize that the correlation between the ABO blood system and susceptibility to SARS-CoV-2 infection can be presumably explained by the modulation of sialic acid-containing receptors distribution on host cell surface induced by ABO antigens through carbohydrate-carbohydrate interactions, which could maximize or minimize the virus Spike protein binding to the host cell. This model could explain previous sparse observations on the molecular mechanism of infection and can direct future research to better understand of COVID-19 pathophysiology.

N-glycosylation of High Mobility Group Box 1 protein (HMGB1) modulates the interaction with glycyrrhizin: A molecular modeling study

High Mobility Group Box 1 protein (HMGB1) is an abundant protein with multiple functions in cells, acting as a DNA chaperone and damage-associated molecular pattern molecule. It represents an attractive target for the treatment of inflammatory diseases and cancers. The plant natural product glycyrrhizin (GLR) is a well-characterized ligand of HMGB1 and a drug used to treat diverse liver and skin diseases. The drug is known to bind to each of the two adjacent HMG boxes of the non-glycosylated protein. In cells, HMGB1 is N-glycosylated at three asparagine residues located in boxes A and B, and these N-glycans are essential for the nucleocytoplasmic transport of the protein. But the impact of the N-glycans on drug binding is unknown. Here we have investigated the effect of the N-glycosylation of HMGB1 on its interaction with GLR using molecular modelling, after incorporation of three N-glycans on a Human HMGB1 structure (PDB code 2YRQ). Sialylated bi-antennary N-glycans were introduced on the protein and exposed in a folded or an extended conformation for the drug binding study. The docking of the drug was performed using both 18α- and 18β-epimers of GLR and the conformations and potential energy of interaction (ΔE) of the different drug-protein complexes were compared. The N-glycans do not shield the drug binding sites on boxes A and B but can modulate the drug-protein interaction, via both direct and indirect effects. The calculations indicate that binding of 18α/β-GLR to the HMG box is generally reduced when the protein is N-glycosylated vs. the non-glycosylated protein. In particular, the N-glycans in an extended configuration significantly weaken the binding of GLR to box-B. The effects of the N-glycans are mostly indirect, but in one case a direct contact with the drug, via a carbohydrate-carbohydrate interaction, was observed with 18β-GLR bound to Box-B of glycosylated HMGB1. For the first time, it is shown (at least in silico) that N-glycosylation, one of the many post-translational modifications of HMGB1, can affect drug binding.

Assembly of Water‐Soluble Sugar‐Coated AIE‐Active Fluorescent Organic Nanoparticles for the Detection of Ginsenosides Based on Carbohydrate‐Carbohydrate Interactions

AbstractA series of water‐soluble turn–on fluorescent organic nanoparticles (FONs) were designed and assembled for the detection of ginsenosides based on carbohydrate‐carbohydrate interactions (CCIs) and aggregation‐induced emission mechanism. Especially, the tetraphenylethylene luminogen coated by four sialic acids (TPE4S) exhibited a considerably high fluorescence enhancement (32‐fold) upon addition of polyglycosylated protopanaxadiol (PPD) derivatives. It is the first time that CCIs were employed for probing amphiphilic ginsenosides effectively. Our current results provide a novel sensing strategy using water‐soluble FONs to detect widely existing saponins with important biological activities.

Diversiform and Transformable Glyco-Nanostructures Constructed from Amphiphilic Supramolecular Metallocarbohydrates through Hierarchical Self-Assembly: The Balance between Metallacycles and Saccharides.

During the past decade, self-assembly of saccharide-containing amphiphilic molecules toward bioinspired functional glycomaterials has attracted continuous attention due to their various applications in fundamental and practical areas. However, it still remains a great challenge to prepare hierarchical glycoassemblies with controllable and diversiform structures because of the complexity of saccharide structures and carbohydrate-carbohydrate interactions. Herein, through hierarchical self-assembly of modulated amphiphilic supramolecular metallocarbohydrates, we successfully prepared various well-defined glyco-nanostructures in aqueous solution, including vesicles, solid spheres, and opened vesicles depending on the molecular structures of metallocarbohydrates. More attractively, these glyco-nanostructures can further transform into other morphological structures in aqueous solutions such as worm-like micelles, tubules, and even tupanvirus-like vesicles (TVVs). It is worth mentioning that distinctive anisotropic structures including the opened vesicles (OVs) and TVVs were rarely reported in glycobased nano-objects. This intriguing diversity was mainly controlled by the subtle structural trade-off of the two major components of the amphiphiles, i.e., the saccharides and metallacycles. To further understand this precise structural control, molecular simulations provided deep physical insights on the morphology evolution and balancing of the contributions from saccharides and metallacycles. Moreover, the multivalency of glyco-nanostructures with different shapes and sizes was demonstrated by agglutination with a diversity of sugar-binding protein receptors such as the plant lectins Concanavalin A (ConA). This modular synthesis strategy provides access to systematic tuning of molecular structure and self-assembled architecture, which undoubtedly will broaden our horizons on the controllable fabrication of biomimetic glycomaterials such as biological membranes and supramolecular lectin inhibitors.

Water-soluble Glucosamine-coated AIE-Active Fluorescent Organic Nanoparticles: Design, Synthesis and Assembly for Specific Detection of Heparin Based on Carbohydrate-Carbohydrate Interactions.

Two water-soluble carbohydrate-coated AIE-activate fluorescent organic nanoparticles TPE3G and TPE4G were designed and synthesized for the detection of heparin. Different from the reported strategy, we not only utilized the general detection mechanism of electrostatic interactions, but also introduced the concept of carbohydrate-carbohydrate interactions (CCIs) to enrich the detection mechanism of heparin. TPE3G can serve as an efficient "turn-on" probe with higher selectivity towards heparin than TPE4G. TEM studies revealed that the micro-aggregated TPE3G was encapsulated with the heparin chain to form a complex self-assemblied composite and emits strong fluorescence. It is believed that the results illustrated in this study provide a novel strategy based on CCls to design water-soluble and more efficient bio-probes for various biological and clinical applications.

Chemoselectivity of Pristine Cellulose Nanocrystal Films Driven by Carbohydrate-Carbohydrate Interactions.

Biological photonic nanostructures comprising a hierarchically self-assembled cellulose nanocrystal (CNC) have been exploited for the development of sensing, optoelectronics, and energy materials. Although multiple techniques are used for controlling the optical response and chiral nematic structure of CNC-derived materials, the presence of external studies that pristine CNC has chemoselectivity is not yet reported to implement this destination. Here, we report that the CNC film without modification shows a high optical sensitivity for glucose through color variation from blue to red. Moreover, various glucose homologs or analogs that only differ in terms of the orientation of a hydroxyl group are selectively distinguished through the naked eye. The excellent chemoselectivity of CNC is attributed to carbohydrate-carbohydrate selective hydrogen-bonding interactions. Close binding with glucose induces the rearrangement of a CNC chain and strengthens the repulsive interaction, thus increasing the helical pitch of the chiral nematic structure of the CNC film and changing its macroscopic color. This CNC chemoselectivity presents an unprecedented control of chiral nematic mesoporous carbon through monosaccharide species. The results provide a simple but highly efficient method to tune the optical and structural properties of CNC nanomaterials and to apply them for practical biosensors, chiral separation, and energy applications.

Blood Type Diets (BTD) and Aging: An Overview

It has recently been proposed that glycans, being the third alphabet of life, interact intricately with endogenous biomolecules to modulate tolerance, immune and inflammatory responses. Specifically, food glycans could impact health and be a source of inflammation and age-related diseases. These special carbohydrates are present as glycoconjugates (glycoproteins or glycolipids) in and on the surface of all the cells (glycocalyx) of all organisms or are found in free form in biological fluids. Recent advances in glycobiology and glycochemistry have shown how glycans bind with naturally present human proteins (lectins), through protein-carbohydrate interactions (or PCI), but also how oligosaccharides can interact with other glycans, present throughout the human body (through carbohydrate-carbohydrate interactions, or CCI). Oligosaccharides present in food sources, which go beyond the definition of normal fibers, once ingested are then either absorbed in the bloodstream, where they are recognized by the immune system, or interact with the surface of GI epithelial cells, thus generating appropriate biochemical cascades that induce a tolerance or immune/inflammatory response. Because the ABO epitopes have been encountered on all human cells, not just erythrocytes and based on the different biotypology (A, AB, B, and O) impose morphic changes in the distribution of the glycans on the glycocalyx (lipid rafts and clustered saccharide patches), their CCI with food and microbe glycans will be different, thus, eliciting contrasting responses. This can explain the epidemiological data for blood type diets (BTD). Through continuous consumption of the wrong types of glycans, processes of chronic inflammation could be initiated and progress to accelerated aging. Four basic modes of action have been identified showing how glycans can trigger inflamm-aging. Since glycobiology is a young science, further studies with newer technologies are warranted for advancement in this field.