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Current Medicinal Chemistry Nov 2017Lectins are a large group of proteins found in animals, plants, fungi, and bacteria that recognize specific carbohydrate targets and play an important role in cell... (Review)
Review
Lectins are a large group of proteins found in animals, plants, fungi, and bacteria that recognize specific carbohydrate targets and play an important role in cell recognition and communication, host-pathogen interactions, embryogenesis, and tissue development. Recently, lectins have emerged as important biomedical tools that have been used in the development of immunomodulatory, antipathogenic, and anticancer agents. Several lectins have been shown to have the ability to discriminate between normal cells and tumor cells as a result of their different glycosylation patterns. Furthermore, the specific binding of lectins to cancer cells has been shown to trigger mechanisms that can promote the death of these abnormal cells. Here, we review the importance of lectins-carbohydrates interactions in cancer therapy and diagnosis. We examine the use of lectins in the modification of nanoparticles (liposomes, solid lipid nanoparticles and other polymers) for anticancer drug delivery. The development of drug delivery systems (liposomes, alginate/chitosan microcapsules, alginate beads) carrying some antitumor lectins is also discussed. In these cases, the processes of cell death induced by these antitumor lectins were also showed (if available). In both cases (lectin-conjugated polymers or encapsulated lectins), these new pharmaceutical preparations showed improved intracellular delivery, bioavailability and targetability leading to enhanced therapeutic index and significantly less side effects.
Topics: Amino Sugars; Antineoplastic Agents; Apoptosis; Biosensing Techniques; Drug Carriers; Glycosylation; Humans; Lectins; Nanoparticles; Neoplasms
PubMed: 28545372
DOI: 10.2174/0929867324666170523110400 -
Cancer Letters Nov 2022Immunoglobulin G (IgG) is the predominant component in humoral immunity and the major effector of neutralizing heterogeneous antigens. Glycosylation, as excessive... (Review)
Review
Immunoglobulin G (IgG) is the predominant component in humoral immunity and the major effector of neutralizing heterogeneous antigens. Glycosylation, as excessive posttranscriptional modification, can modulate IgG immune function. Glycosylated IgG has been reported to correlate with tumor progression, presenting several characteristic modifications, including the core fucose, galactose, sialic acid, and the bisect N-acetylglucosamine (GlcNAc). Meanwhile, IgG glycosylation regulates tumor immunity involved in tumor progression and is thus a potential target. Herein, we summarized the research progression to provide novel insight into the application of IgG glycosylation in tumor diagnosis and treatment.
Topics: Acetylglucosamine; Fucose; Galactose; Glycosylation; Humans; Immunoglobulin G; N-Acetylneuraminic Acid; Neoplasms
PubMed: 36096412
DOI: 10.1016/j.canlet.2022.215902 -
Trends in Microbiology Dec 2016Sialic acids (Sias) are abundantly displayed on the surfaces of vertebrate cells, and particularly on all mucosal surfaces. Sias interact with microbes of many types,... (Review)
Review
Sialic acids (Sias) are abundantly displayed on the surfaces of vertebrate cells, and particularly on all mucosal surfaces. Sias interact with microbes of many types, and are the targets of specific recognition by many different viruses. They may mediate virus binding and infection of cells, or alternatively can act as decoy receptors that bind virions and block virus infection. These nine-carbon backbone monosaccharides naturally occur in many different modified forms, and are attached to underlying glycans through varied linkages, creating significant diversity in the pathogen receptor forms. Here we review the current knowledge regarding the distribution of modified Sias in different vertebrate hosts, tissues, and cells, their effects on viral pathogens where those have been examined, and outline unresolved questions.
Topics: Animals; Avulavirus; Host-Pathogen Interactions; Humans; N-Acetylneuraminic Acid; Polysaccharides; Receptors, Virus; Sialic Acids; Viral Tropism; Virion; Virus Attachment
PubMed: 27491885
DOI: 10.1016/j.tim.2016.07.005 -
Applied and Environmental Microbiology May 2019-Acetylglucosamine (GlcNAc) and glucosamine (GlcN) enhance the competitiveness of the laboratory strain DL1 of against the caries pathogen Here, we examine how amino...
-Acetylglucosamine (GlcNAc) and glucosamine (GlcN) enhance the competitiveness of the laboratory strain DL1 of against the caries pathogen Here, we examine how amino sugars affect the interaction of five low-passage-number clinical isolates of abundant commensal streptococci with by utilizing a dual-species biofilm model. Compared to that for glucose, growth on GlcN or GlcNAc significantly reduced the viability of in cocultures with most commensals, shifting the proportions of species. Consistent with these results, production of HO was increased in most commensals when growing on amino sugars, and inhibition of by , , or was enhanced by amino sugars on agar plates. All commensals except had higher arginine deiminase activities when grown on GlcN and, in some cases, GlcNAc. In biofilms formed using pooled cell-containing saliva (CCS), the proportions of were drastically diminished when GlcNAc was the primary carbohydrate. Increased production of HO could account in large part for the inhibitory effects of CCS biofilms. Surprisingly, amino sugars appeared to improve mutacin production by on agar plates, suggesting that the commensals have mechanisms to actively subvert antagonism by in cocultures. Collectively, these findings demonstrate that amino sugars can enhance the beneficial properties of low-passage-number commensal oral streptococci and highlight their potential for moderating the cariogenicity of oral biofilms. Dental caries is driven by dysbiosis of oral biofilms in which dominance by acid-producing and acid-tolerant bacteria results in loss of tooth mineral. Our previous work demonstrated the beneficial effects of amino sugars GlcNAc and GlcN in promoting the antagonistic properties of a health-associated oral bacterium, , in competition with the major caries pathogen Here, we investigated 5 low-passage-number clinical isolates of the most common streptococcal species to establish how amino sugars may influence the ecology and virulence of oral biofilms. Using multiple models, including a human saliva-derived microcosm biofilm, experiments showed significant enhancement by at least one amino sugar in the ability of most of these bacteria to suppress the caries pathogen. Therefore, our findings demonstrated the mechanism of action by which amino sugars may affect human oral biofilms to promote health.
Topics: Amino Sugars; Biofilms; Dental Caries; Dental Plaque; Saliva; Streptococcal Infections; Streptococcus gordonii; Streptococcus mutans; Symbiosis
PubMed: 30877119
DOI: 10.1128/AEM.00370-19 -
Chemical Record (New York, N.Y.) Oct 2021Carbohydrate-protein interactions are involved in a myriad of biological processes. Thus, glycomimetics have arisen as one of the most promising synthetic targets to... (Review)
Review
Carbohydrate-protein interactions are involved in a myriad of biological processes. Thus, glycomimetics have arisen as one of the most promising synthetic targets to that end. Within the broad variety of glycomimetics, thiodisaccharides have proven to be excellent tools to study these processes, and even more, some of them unveiled interesting biological activities. This review brings together research made on the introduction of N-acetylhexosamine residues into thiodisaccharides to date, passing through classic substitution (as S 2, thioglycosylation and ring-opening reactions) and addition (as thiol-ene coupling and Michael-type additions) reactions. Recent and interesting developments regarding addition reactions to vinyl azides, cross-coupling reactions and novel chemoenzymatic methods are also discussed.
Topics: Hexosamines
PubMed: 34170606
DOI: 10.1002/tcr.202100146 -
Journal of Immunology (Baltimore, Md. :... Nov 2023Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus...
Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic β cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated β cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Glucosamine; Acetylglucosamine; Pancreas
PubMed: 37747293
DOI: 10.4049/jimmunol.2300264 -
The Science of the Total Environment Jan 2024Soil microbial necromass is an important contributor to soil organic matter (>50%) and it is largely composed of microbial residues. In soils, fragmented cell wall...
Soil microbial necromass is an important contributor to soil organic matter (>50%) and it is largely composed of microbial residues. In soils, fragmented cell wall residues are mostly found in their polysaccharide forms of fungal chitin and bacterial peptidoglycan. Microbial necromass biomarkers, particularly amino sugars (AS) such as glucosamine (GlcN) and muramic acid (MurA) have been used to trace fungal and bacterial residues in soils, and to distinguish carbon (C) found in microbial residues from non-microbial organic C. Neutral sugars (NS), particularly the hexose/pentose ratio, have also been proposed as tracers of plant polysaccharides in soils. In our study, we extended the range of biomarkers to include AS and NS compounds in the biomass of 120 species belonging to archaea, bacteria, fungi, or plants. GlcN was the most common AS found in all taxa, contributing 42-91% to total AS content, while glucose was the most common NS found, contributing 56-79% to total NS. We identified talosaminuronic acid, found in archaeal pseudopeptidoglycan, as a new potential biomarker specific for Euryarchaeota. We compared the variability of these compounds between the different taxonomic groups using multivariate approaches, such as non-metric multidimensional scaling (NMDS) and partial least squares discriminant analysis (PLS-DA) and statistically evaluated their biomarker potential via indicator species analysis. Both NMDS and PLS-DA showcased the variability in the AS and NS contents between the different taxonomic groups, highlighting their potential as necromass residue biomarkers and allowing their extension from separating bacterial and fungal necromass to separating microbes from plants. Finally, we estimated new conversion factors where fungal GlcN is converted to fungal C by multiplying by 10 and MurA is converted to bacterial C by multiplying by 54. Conversion factors for talosaminuronic acid and galactosamine are also proposed to allow estimation of archaeal or all-microbial necromass residue C, respectively.
Topics: Archaea; Sugars; Carbohydrates; Amino Sugars; Bacteria; Carbon; Fungi; Soil; Biomarkers; Soil Microbiology
PubMed: 37793447
DOI: 10.1016/j.scitotenv.2023.167463 -
Scientific Reports Sep 2016The nitrogen-metabolic phosphotransferase system, PTS(Ntr), consists of the enzymes I(Ntr), NPr and IIA(Ntr) that are encoded by ptsP, ptsO, and ptsN, respectively. Due...
The nitrogen-metabolic phosphotransferase system, PTS(Ntr), consists of the enzymes I(Ntr), NPr and IIA(Ntr) that are encoded by ptsP, ptsO, and ptsN, respectively. Due to the proximity of ptsO and ptsN to rpoN, the PTS(Ntr) system has been postulated to be closely related with nitrogen metabolism. To define the correlation between PTS(Ntr) and nitrogen metabolism, we performed ligand fishing with EIIA(Ntr) as a bait and revealed that D-glucosamine-6-phosphate synthase (GlmS) directly interacted with EIIA(Ntr). GlmS, which converts D-fructose-6-phosphate (Fru6P) into D-glucosamine-6-phosphate (GlcN6P), is a key enzyme producing amino sugars through glutamine hydrolysis. Amino sugar is an essential structural building block for bacterial peptidoglycan and LPS. We further verified that EIIA(Ntr) inhibited GlmS activity by direct interaction in a phosphorylation-state-dependent manner. EIIA(Ntr) was dephosphorylated in response to excessive nitrogen sources and was rapidly degraded by Lon protease upon amino sugar depletion. The regulation of GlmS activity by EIIA(Ntr) and the modulation of glmS translation by RapZ suggest that the genes comprising the rpoN operon play a key role in maintaining amino sugar homeostasis in response to nitrogen availability and the amino sugar concentration in the bacterial cytoplasm.
Topics: Amino Sugars; Bacterial Proteins; Cytoplasm; Fructosephosphates; Glucosamine; Glucose-6-Phosphate; Homeostasis; Nitrogen; Phosphoenolpyruvate Sugar Phosphotransferase System; Phosphorylation; Salmonella typhimurium
PubMed: 27628932
DOI: 10.1038/srep33055 -
Proceedings of the National Academy of... Feb 2019Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of...
Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with ,'-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.
Topics: Amino Sugars; Binding Sites; Blood Proteins; Cell Adhesion; Cell Proliferation; Galectin 1; Galectin 3; Galectins; Glycoconjugates; Humans; Lactose; Ligands; Nanoparticles; Polysaccharides
PubMed: 30718416
DOI: 10.1073/pnas.1813515116 -
Analytical Chemistry Sep 2017Soil fluxomics analysis can provide pivotal information for understanding soil biochemical pathways and their regulation, but direct measurement methods are rare. Here,...
Soil fluxomics analysis can provide pivotal information for understanding soil biochemical pathways and their regulation, but direct measurement methods are rare. Here, we describe an approach to measure soil extracellular metabolite (amino sugar and amino acid) concentrations and fluxes based on a N isotope pool dilution technique via liquid chromatography and high-resolution mass spectrometry. We produced commercially unavailable N and C labeled amino sugars and amino acids by hydrolyzing peptidoglycan isolated from isotopically labeled bacterial biomass and used them as tracers (N) and internal standards (C). High-resolution (Orbitrap Exactive) MS with a resolution of 50 000 allowed us to separate different stable isotope labeled analogues across a large range of metabolites. The utilization of C internal standards greatly improved the accuracy and reliability of absolute quantification. We successfully applied this method to two types of soils and quantified the extracellular gross fluxes of 2 amino sugars, 18 amino acids, and 4 amino acid enantiomers. Compared to the influx and efflux rates of most amino acids, similar ones were found for glucosamine, indicating that this amino sugar is released through peptidoglycan and chitin decomposition and serves as an important nitrogen source for soil microorganisms. d-Alanine and d-glutamic acid derived from peptidoglycan decomposition exhibited similar turnover rates as their l-enantiomers. This novel approach offers new strategies to advance our understanding of the production and transformation pathways of soil organic N metabolites, including the unknown contributions of peptidoglycan and chitin decomposition to soil organic N cycling.
PubMed: 28776982
DOI: 10.1021/acs.analchem.7b01938