ABSTRACT
Tuberculosis (TB) continues to pose a grave threat to global health, despite relentless eradication efforts. In 1882, Robert Koch discovered that Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing tuberculosis. It is a fact that tuberculosis has claimed the lives of more than one billion people in the last few decades. It is imperative that we must take immediate and effective action to increase resources for TB research and treatment. Effective TB treatments demand an extensive investment of both time and finances, often requiring 6-9 months of rigorous antibiotic therapy. The most efficient way to control tuberculosis is by receiving a childhood Bacillus Calmette-Guérin (BCG) vaccination. Despite years of research on vaccine development, we still do not have any new approved vaccine for tuberculosis, except BCG, which is partially effective in young children. This review discusses briefly the available treatment for tuberculosis and remarkable advancements in glycoconjugate-based TB vaccine developments in recent years (2013-2024) and offers valuable direction for future research priorities.
Subject(s)
Antitubercular Agents , Glycoconjugates , Mycobacterium tuberculosis , Tuberculosis , Humans , Tuberculosis/prevention & control , Tuberculosis/drug therapy , Glycoconjugates/chemistry , Glycoconjugates/chemical synthesis , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Tuberculosis Vaccines/therapeutic use , Vaccine Development , Molecular Structure , AnimalsABSTRACT
Carbohydrate-based self-assembling systems are essential for the formation of advanced biocompatible materials via a bottom-up approach. The self-assembling of sugar-based small molecules has applications encompassing many research fields and has been studied extensively. In this focused review, we will discuss the synthetic approaches for carbohydrate-based self-assembling (SA) systems, the mechanisms of the assembly, as well as the main properties and applications. This review will mainly cover recent publications in the last four years from January 2020 to December 2023. We will essentially focus on small molecule self-assembly, excluding polymer-based systems, which include various derivatives of monosaccharides, disaccharides, and oligosaccharides. Glycolipids, glycopeptides, and some glycoconjugate-based systems are discussed. Typically, in each category of systems, the system that can function as low molecular weight gelators (LMWGs) will be discussed first, followed by self-assembling systems that produce micelles and aggregates. The last section of the review discusses stimulus-responsive self-assembling systems, especially those forming gels, including dynamic covalent assemblies, chemical-triggered systems, and photoresponsive systems. The review will be organized based on the sugar structures, and in each category, the synthesis of representative molecular systems will be discussed next, followed by the properties of the resulting molecular assemblies.
Subject(s)
Carbohydrates , Carbohydrates/chemistry , Carbohydrates/chemical synthesis , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Glycolipids/chemistry , Glycolipids/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesisABSTRACT
As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis and early bactericidal tests of two luminescent glycoconjugates whose basic structure is characterized by two boron dipyrromethene difluoride (BODIPY) moieties and three galactoside rings mounted on an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches of biology in the last few decades. In particular, molecular platforms showing two different BODIPY groups have unique photophysical behavior useful in fluorescence imaging. Construction of the complex architecture of the new probes is accomplished through a convergent route that exploits a series of copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to the proliferation of bacterial infections, in conjunction with growing antibiotic resistance, requires the production of new multifunctional drugs and efficient methods for their targeted delivery to control bacteria-associated diseases. Preliminary studies of the glycoconjugate properties as antibacterial agents against representatives of Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) pathogens, which are associated with chronic infections, indicated significant bactericidal activity ascribable to their structural features.
Subject(s)
Anti-Bacterial Agents , Boron Compounds , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Boron Compounds/chemistry , Boron Compounds/pharmacology , Boron Compounds/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Glycoconjugates/chemical synthesis , Molecular Structure , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesisABSTRACT
Introducing glycans represents an efficient chemical approach to improve the pharmacological properties of therapeutic biomolecules. Herein, we report an efficient synthesis of glycoconjugates through chlorooxime-thiol conjugation. The reactive glycosyl chlorooximes, derived from pyranoses or furanoses, readily couple to a wide range of thiol-containing substrates, including peptides, sugars, and thiophenols. This method features mild reaction conditions and fast kinetics. Capability for aqueous media and gram-scale synthesis demonstrates the potential of this method in the bioconjugation of saccharides with biologically active molecules.
Subject(s)
Glycoconjugates , Oximes , Sulfhydryl Compounds , Oximes/chemistry , Glycoconjugates/chemistry , Glycoconjugates/chemical synthesis , Sulfhydryl Compounds/chemistry , Molecular StructureABSTRACT
Neoglycoconjugates mimicking natural compounds and possessing a variety of biological functions are very successful tools for researchers to understand the general mechanisms of many biological processes in living organisms. These substances are characterized by high biotolerance and specificity, with low toxicity. Due to the difficult isolation of individual glycoclusters from biological objects, special interest has been directed toward synthetic analogs. This review is mainly focused on the one-pot, double-click methodology (containing alkyne-azide click cycloaddition with the following 6π-azaelectrocyclization reactions) used in the synthesis of N-glycoconjugates. Homogeneous (including one type of biantennary N-glycan fragments) and heterogeneous (containing two to four types of biantennary N-glycan fragments) glycoclusters on albumin were synthesized via this strategy. A series of cell-, tissue- and animal-based experiments proved glycoclusters to be a very promising class of targeted delivery systems. Depending on the oligosaccharide units combined in the cluster, their amount, and arrangement relative to one another, conjugates can recognize various cells, including cancer cells, with high selectivity. These results open new perspectives for affected tissue visualization and treatment.
Subject(s)
Glycoconjugates/chemical synthesis , Polysaccharides/chemistry , Serum Albumin, Human/chemistry , Animals , Catalysis , Chemistry Techniques, Synthetic , Click Chemistry , Glycoconjugates/chemistry , Humans , Lectins/chemistry , Mice , Models, Molecular , Molecular Conformation , Molecular Structure , Structure-Activity RelationshipABSTRACT
A series of new colchicine glycoconjugates as tubulin polymerization inhibitors were designed by targeting strategy based on Warburg effect. All of the colchicine glycoconjugates were synthesized and then evaluated for their antiproliferative activities against three human cancer lines HT-29, MCF-7 and Hep-3B. Among them, 1e exhibited greater than 10 times selectivity between GLUT1 highly expressed cells (HT-29 and MCF-7) and GLUT1 lowly expressed cells (Hep-3B), and also showed lower cytotoxicity against HUVECs compared with colchicine. Moreover, 1e significantly inhibited tubulin polymerization and disrupted microtubule networks. GLUT1 inhibitor-dependent cytotoxicity assay demonstrated that the uptake of 1e was regulated via GLUT1. Molecular docking studies showed that 1e could be a substrate of GLUT1 and bind to the colchicine site of tubulin.
Subject(s)
Antineoplastic Agents/pharmacology , Colchicine/pharmacology , Drug Design , Glycoconjugates/pharmacology , Tubulin Modulators/pharmacology , Tubulin/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Colchicine/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Humans , Molecular Docking Simulation , Molecular Structure , Polymerization/drug effects , Structure-Activity Relationship , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistryABSTRACT
The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy. Glycoconjugates consisting of three basic building blocks: a sugar unit, a linker containing a 1,2,3-triazole ring, and an 8-hydroxyquinoline fragment was described earlier. It is not known whether their cytotoxicity is due to whole glycoconjugates action or their metabolites. To check the biological activity of products that can be released from glycoconjugates under the action of hydrolytic enzymes, the synthetically obtained potential metabolites were tested in vitro for the inhibition of proliferation of HCT-116, MCF-7, and NHDF-Neo cell lines using the MTT assay. Research shows that for the full activity of glycoconjugates, the presence of all three building blocks in the structure of a potential drug is necessary. For selected derivatives, additional tests of targeted drug delivery to tumor cells were carried out using polymer nanocarriers in which they are encapsulated. This approach significantly lowered the determined IC50 values of the tested compounds and improved their selectivity and effectiveness.
Subject(s)
Antineoplastic Agents/pharmacology , Glycoconjugates/pharmacology , Prodrugs/pharmacology , Quinolines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Glycoconjugates/metabolism , Humans , MCF-7 Cells , Neoplasms/drug therapy , Neoplasms/metabolism , Prodrugs/chemical synthesis , Prodrugs/chemistry , Prodrugs/metabolism , Quinolines/chemical synthesis , Quinolines/chemistry , Quinolines/metabolism , Structure-Activity RelationshipABSTRACT
Insights into the differential binding characteristics of anti-Lea and anti-LeaLex monoclonal antibodies (mAbs) provide information to develop LeaLex-based cancer immunotherapeutics while avoiding anti-Lea autoimmune reactions. We characterized the epitope recognized by anti-Lea mAb SPM 522. We synthesized the Lea 6-aminohexyl glycoside and report experimental evidence of a minor conformation in solution. The Lea and three other 6-aminohexyl glycosides were conjugated to BSA and titration experiments with SPM 522 show that: 1. SPM 522 binds to LeaLex better than to Lea; 2. the non-reducing Lea galactosyl residue is essential to binding. Competitive ELISA experiments using a panel of tri- to pentasaccharide fragments of LeaLex as well as Lea analogues indicate that: 1. the Lea ß-d-galactosyl α hydrophobic patch is crucial to binding; 2. the Lea fucosyl residue contributes to binding; 3. the Lexd-galactosyl residue also contributes to binding. These results indicate that anti-Lea mAb SPM 522 recognizes the Lea[1,3]-ß-d-Gal tetrasaccharide. We propose that a major recognition element is the extended hydrophobic surface defined by the Lea-ß-d-Gal residue extending to the α faces of the ß-d-GlcNAc and ß-d-Gal residues.
Subject(s)
Antibodies, Monoclonal/immunology , Epitopes/immunology , Glycoconjugates/immunology , Antibodies, Monoclonal/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
Extraintestinal pathogenic Escherichia coli O1 is a frequently identified serotype that causes serious infections and is often refractory to antimicrobial therapy. Glycoconjugate vaccine represents a promising measure to reduce ExPEC infections. Herein, we designed an O1-specific glyco-optimized chassis strain for manufacture of O-polysaccharide (OPS) antigen and OPS-based bioconjugate. Specifically, OPS and OPS-based glycoprotein were synthesized in glyco-optimized chassis strain, when compared to the unmeasurable level of the parent strain. The optimal expression of oligosaccharyltransferase and carrier protein further improved the titer. MS analysis elucidated the correct structure of resulting bioconjugate at routine and unreported glycosylation sequons of carrier protein, with a higher glycosylation efficiency. Finally, purified bioconjugate stimulated mouse to generate specific IgG antibodies and protected them against virulent ExPEC O1 challenge. The plug-and-play glyco-optimized platform is suitable for bioconjugate synthesis, thus providing a potential platform for future medical applications.
Subject(s)
Anti-Bacterial Agents/pharmacology , Extraintestinal Pathogenic Escherichia coli/drug effects , Glycoconjugates/pharmacology , Polysaccharides/pharmacology , Protein Engineering , Vaccines, Conjugate/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Drug Development , Female , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Mice , Microbial Sensitivity Tests , Polysaccharides/chemical synthesis , Polysaccharides/chemistry , Vaccines, Conjugate/chemistryABSTRACT
While the improved treatment of human immunodeficiency virus type 1 (HIV-1) infection is available, the development of an effective and safe prophylactic vaccine against HIV-1 is still an unrealized goal. Encouragingly, the discovery of broadly neutralizing antibodies (bNAbs) from HIV-1 positive patients that are capable of neutralizing a broad spectrum of HIV-1 isolates of various clades has accelerated the progress of vaccine development in the past few years. Some of these bNAbs recognize the N-glycans on the viral surface gp120 glycoprotein. We have been interested in using the glycan epitopes recognized by bNAbs for the development of vaccines to elicit bNAb-like antibodies with broadly neutralizing activities. Toward this goal, we have identified novel hybrid-type structures with subnanomolar avidity toward several bNAbs including PG16, PGT121, PGT128-3C, 2G12, VRC13, VRC-PG05, VRC26.25, VRC26.09, PGDM1400, 35O22, and 10-1074. Here, we report the immunogenicity evaluation of a novel hybrid glycan conjugated to carrier DTCRM197, a nontoxic mutant of the diphtheria toxin, for immunization in mice. Our results indicated that the IgG response was mainly against the chitobiose motif with nonspecific binding to a panel of N-glycans with reducing end GlcNAc-GlcNAc (chitobiose) printed on the glass slides. However, the IgM response was mainly toward the reducing end GlcNAc moiety. We further used the glycoconjugates of Man3GlcNAc2, Man5GlcNAc2, and Man9GlcNAc2 glycans for immunization, and a similar specificity pattern was observed. These findings suggest that the immunogenicity of chitobiose may interfere with the outcome of N-glycan-based vaccines, and modification may be necessary to increase the immunogenicity of the entire N-glycan epitope.
Subject(s)
AIDS Vaccines/immunology , Broadly Neutralizing Antibodies/immunology , Glycoconjugates/immunology , HIV Antibodies/immunology , Polysaccharides/immunology , Acetylglucosamine/immunology , Animals , Bacterial Proteins/chemistry , Carbohydrate Sequence , Disaccharides/immunology , Epitopes , Female , Glycoconjugates/chemical synthesis , HIV-1/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Mice, Inbred C57BL , Polysaccharides/chemical synthesis , Vaccine DevelopmentABSTRACT
In this review, we discuss structural diversity, taxonomic distribution, biological activities, biogenesis, and synthesis of a rare group of terpenoids, the so-called malabaricane and isomalabaricane triterpenoids, as well as some compounds derived from them. Representatives of these groups were found in some higher and lower terrestrial plants, as well as in some fungi, and in a relatively small group of marine sponges. The skeletal systems of malabaricanes and isomalabaricanes are similar to each other, but differ principally in the stereochemistry of their tricyclic core fragments, consisting of two six-membered and one five-membered rings. Evolution of these triterpenoids provides variety of rearranged, oxidized, and glycoconjugated products. These natural compounds have attracted a lot of attention for their biosynthetic origin and biological activity, especially for their extremely high cytotoxicity against tumor cells as well as promising neuroprotective properties in nanomolar concentrations.
Subject(s)
Triterpenes , Animals , Biosynthetic Pathways , Fungi/chemistry , Fungi/metabolism , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Glycoconjugates/metabolism , Plants/chemistry , Plants/metabolism , Porifera/chemistry , Porifera/metabolism , Triterpenes/chemical synthesis , Triterpenes/chemistry , Triterpenes/metabolismABSTRACT
The C-type lectin receptor DC-SIGN mediates interactions with envelope glycoproteins of many viruses such as SARS-CoV-2, ebola, and HIV and contributes to virus internalization and dissemination. In the context of the recent SARS-CoV-2 pandemic, involvement of DC-SIGN has been linked to severe cases of COVID-19. Inhibition of the interaction between DC-SIGN and viral glycoproteins has the potential to generate broad spectrum antiviral agents. Here, we demonstrate that mannose-functionalized poly-l-lysine glycoconjugates efficiently inhibit the attachment of viral glycoproteins to DC-SIGN-presenting cells with picomolar affinity. Treatment of these cells leads to prolonged receptor internalization and inhibition of virus binding for up to 6â h. Furthermore, the polymers are fully bio-compatible and readily cleared by target cells. The thermodynamic analysis of the multivalent interactions reveals enhanced enthalpy-driven affinities and promising perspectives for the future development of multivalent therapeutics.
Subject(s)
Antiviral Agents/pharmacology , Cell Adhesion Molecules/antagonists & inhibitors , Glycoconjugates/pharmacology , Lectins, C-Type/antagonists & inhibitors , Receptors, Cell Surface/antagonists & inhibitors , Virus Attachment/drug effects , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Cell Adhesion Molecules/metabolism , Glycoconjugates/chemical synthesis , Glycoconjugates/metabolism , Humans , Lectins, C-Type/metabolism , Mannose/analogs & derivatives , Mannose/metabolism , Mannose/pharmacology , Microbial Sensitivity Tests , Polylysine/analogs & derivatives , Polylysine/metabolism , Polylysine/pharmacology , Protein Binding/drug effects , Receptors, Cell Surface/metabolism , SARS-CoV-2/drug effects , THP-1 Cells , Thermodynamics , Viral Envelope Proteins/antagonists & inhibitors , Viral Envelope Proteins/metabolismABSTRACT
A total of forty-three compounds were synthesized, including thirty-two new ones. Among those compounds, seventeen were selected and tested on human tumor cell lines: PC-3 (prostate adenocarcinoma), HCT-116 (colorectal tumor), NCIH-460 (lung carcinoma), SKMEL-103 (melanoma) and AGP-01 (gastric tumor). Alkynylated 1,2,4-oxadiazoles 2m, 3g and 3k exhibited antiproliferative activities against NCIH-460 in culture. Alkynylated N-cyclohexyl-1,2,4-oxadiazoles 3a-m and bis-heterocycle glucoglycero-1,2,3-triazole-N-cyclohexyl-1,2,4-oxadiazole derivatives 5a-k and 6-11 were evaluated for their in vitro efficacy towards Mycobacterium tuberculosis (Mtb) H37Ra and H37Rv strains. In general, glycerosugars conjugated to 1,2,4-oxadiazole via a 1,2,3-triazole linkage (5a, 5e, 5j, 5k, and 7) showed in vitro inhibitory activity against Mtb (H37Rv). The largest molecules bis-triazoles 10 and 11, proved inactive against TB. Probably, the absence of the N-cyclohexyl group in compound 8 and 1,2,4-oxadiazole nucleus in compound 9 were responsible for its low activity. Glucoglycero-triazole-oxadiazole derivatives 5e (10 µM) and 7 (23.9 µM) were the most promising antitubercular compounds, showing a better selective index than when tested against RAW 264.7 and HepG2 cells. Vero cell were used to investigate cytotoxicity of compounds 5a, 5h, 5j, 5k, and these compounds showed good cell viability. Further, in silico studies were performed for most active compounds (5e and 7) with potential drug targets, DprE1 and InhA of Mtb to understand possible interactions aided with molecular dynamic simulation (100ns).
Subject(s)
Antineoplastic Agents/pharmacology , Antitubercular Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Glycoconjugates/pharmacology , Lung Neoplasms/drug therapy , Mycobacterium tuberculosis/drug effects , Oxadiazoles/chemistry , Alkynes/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Discovery , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Triazoles/chemistryABSTRACT
A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural d-configuration. Thus, we were able to obtain the target molecules from the commercially available d-ribose via a shorter and convenient sequence of reactions.
Subject(s)
Antioxidants/chemical synthesis , Glycoconjugates/chemical synthesis , Organoselenium Compounds/chemical synthesis , Selenium/chemistry , Antioxidants/chemistry , Glycoconjugates/chemistry , Humans , Organoselenium Compounds/chemistryABSTRACT
Glycodendrimers have attracted considerable interest in the field of dendrimer sciences owing to their plethora of implications in biomedical applications. This is primarily due to the fact that cell surfaces expose a wide range of highly diversified glycan architectures varying by the nature of the sugars, their number, and their natural multiantennary structures. This particular situation has led to cancer cell metastasis, pathogen recognition and adhesion, and immune cell communications that are implicated in vaccine development. The diverse nature and complexity of multivalent carbohydrate-protein interactions have been the impetus toward the syntheses of glycodendrimers. Since their inception in 1993, chemical strategies toward glycodendrimers have constantly evolved into highly sophisticated methodologies. This review constitutes the first part of a series of papers dedicated to the design, synthesis, and biological applications of heterofunctional glycodendrimers. Herein, we highlight the most common synthetic approaches toward these complex molecular architectures and present modern applications in nanomolecular therapeutics and synthetic vaccines.
Subject(s)
Chemistry Techniques, Synthetic , Dendrimers/chemistry , Dendrimers/pharmacology , Drug Design , Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Carbohydrates/chemistry , Dendrimers/chemical synthesis , Drug Development , Glycoconjugates/chemical synthesis , Humans , Models, Molecular , Molecular Conformation , Molecular Structure , Molecular Targeted Therapy , Structure-Activity RelationshipABSTRACT
Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Nonspecific drug delivery shows limited clinical applications owing to high dosage, cytotoxicity, nonspecific action, high cost, etc. Therefore, targeted delivery of less cytotoxic drug candidates to hepatocytes through ASGPR-mediated endocytosis could be an efficient strategy to surmount the prevailing shortcomings. In the present work, the gene encoding ASGPR-H1-CRD was amplified from Huh7 cells, cloned into pET 11a vector, and the ASGPR-H1-CRD protein was expressed and purified from E. coli. A novel triantennary galactose-conjugated quinoline derivative 4 was synthesized that demonstrates 17-fold higher binding affinity to isolated ASGPR-H1-CRD protein receptor (Kd â¼54â µM) in comparison to D-galactose (Kd â¼900â µM). Moreover, micro-calorimetric studies for the interaction of glycoconjugate 4 with ASGPR protein on live hepatocytes showed notable thermal response in case of ASGPR-containing Huh7 cells, in comparison to non-ASGPR Chang cells. These results might serve as an approach towards targeted delivery of small glycoconjugates to hepatocytes.
Subject(s)
Asialoglycoprotein Receptor/metabolism , Glycoconjugates/pharmacology , Quinolines/pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Humans , Molecular Structure , Quinolines/chemical synthesis , Quinolines/chemistry , Structure-Activity RelationshipABSTRACT
Carbohydrates play important and diverse roles in the fundamental processes of life. We have established a method for accurately and a large-scale synthesis of functional carbohydrates with diverse properties using a unique enzymatic method. Furthermore, various artificial glycan-conjugated molecules have been developed by adding these synthetic carbohydrates to macromolecules and to middle- and low-molecular-weight molecules with different properties. These glycan-conjugated molecules have biological activities comparable to or higher than those of natural compounds and present unique functions. In this review, several synthetic glycan-conjugated molecules are taken as examples to show design, synthesis, and function.
Subject(s)
Antiviral Agents/chemical synthesis , Biological Factors/chemical synthesis , Glycoconjugates/chemical synthesis , Polysaccharides/chemistry , Sialoglycoproteins/chemical synthesis , Animals , Antiviral Agents/pharmacology , Biological Factors/pharmacology , Carbohydrate Conformation , Cheminformatics/methods , Cross-Linking Reagents/chemistry , Drug Design , Glycoconjugates/pharmacology , Glycosides/chemistry , Glycosylation , Humans , Nanoparticles/chemistry , Orthomyxoviridae/drug effects , Orthomyxoviridae/growth & development , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Sialoglycoproteins/pharmacologyABSTRACT
At the surface of many cells is a compendium of glycoconjugates that form an interface between the cell and its surroundings; the glycocalyx. The glycocalyx serves several functions that have captivated the interest of many groups. Given its privileged residence, this meshwork of sugar-rich biomolecules is poised to transmit signals across the cellular membrane, facilitating communication with the extracellular matrix and mediating important signalling cascades. As a product of the glycan biosynthetic machinery, the glycocalyx can serve as a partial mirror that reports on the cell's glycosylation status. The glycocalyx can also serve as an information-rich barrier, withholding the entry of pathogens into the underlying plasma membrane through glycan-rich molecular messages. In this review, we provide an overview of the different approaches devised to engineer glycans at the cell surface, highlighting considerations of each, as well as illuminating the grand challenges that face the next era of 'glyco-engineers'. While we have learned much from these techniques, it is evident that much is left to be unearthed.
Subject(s)
Genetic Engineering/methods , Glycocalyx/physiology , Glycoconjugates/chemistry , Animals , CRISPR-Cas Systems , Click Chemistry , Gene Knockout Techniques , Glycocalyx/chemistry , Glycoconjugates/chemical synthesis , Glycoproteins/metabolism , Glycosylation , Glycosyltransferases/genetics , Humans , Monosaccharides/chemistry , Mucins/metabolism , Oligosaccharides/chemistry , Polysaccharides/metabolism , Protein Engineering/methods , Protein Processing, Post-Translational , RNA, Small Interfering/genetics , Recombinant Proteins/metabolism , Surface PropertiesABSTRACT
Polyacrylamide conjugates of glycans have long been widely used in many research areas of glycobiology, mainly for immobilizing glycans in solid-phase assays and as multivalent inhibitors. Pending biotin tag allows immobilizing Glyc-PAA quantitatively on any surface, and acts as a tracer for detection of carbohydrate-binding proteins. However, the scope of already realized capabilities of these probes is immeasurably richer than those listed above. This review is not so much about routine as about less common, but not less significant applications. Also, the data on the glycopolymers themselves, their molecular weight, size and polymer chain flexibility are presented, as well as the methods of synthesis, clusterisation and entropy factor in their interaction with proteins.
Subject(s)
Acrylic Resins , Glycoconjugates/chemistry , Glycomics/methods , Orthomyxoviridae/metabolism , Acrylic Resins/chemistry , Biotin/chemistry , Biotin/metabolism , Glycoconjugates/chemical synthesis , Molecular Weight , Polysaccharides/chemistry , Polysaccharides/metabolism , Reproducibility of ResultsABSTRACT
In this study, cassava starch aldehyde was functionalized with catechin through acid catalyzed condensation reaction. The structural characterization, stability and antioxidant activity of starch aldehyde-catechin conjugates were investigated. Thin layer chromatography revealed the conjugates did not contain free catechin. UV-vis spectra of the conjugates exhibited an absorption band at 280 nm, attributing to the B-ring of catechin moiety. Fourier-transform infrared and proton nuclear magnetic resonance spectroscopy demonstrated the conjugation occurred between the H-6/H-8 of catechin A-ring and the aldehyde groups of starch aldehyde. X-ray diffraction pattern indicated that the conjugates had an amorphous structure. Scanning electron microscopy showed the conjugates were fragmentary slices with rough surfaces. Notably, the conjugates were more stable than catechin in phosphate buffered saline (pH 7.4). In addition, the conjugates could not be digested in simulated saliva, gastric and small intestinal juices. The reducing power and free radical scavenging activity of starch aldehyde were remarkably elevated by conjugating with catechin. Meanwhile, the conjugates were non-cytotoxic to RAW264.7 mouse macrophage cells and possessed higher resistant starch contents than starch. Our results suggest starch aldehyde-catechin conjugates can be used as antioxidants in food industry.