Explore the vast range of titles available.

The development of general synthetic strategies for the prepartion of oligonucleotides and peptides has enabled them to be made routinely — often using automated systems. Making complex oligosaccharides is much less straightforward, but advances in areas such as one-pot multi-step protecting-group manipulations, stereoselective glycosylation protocols and chemo-enzymatic methods are offering new opportunities for carbohydrate chemistry. Synthetic oligosaccharides and glycoconjugates are increasingly used as probes for biological research and as lead compounds for drug and vaccine discovery. These endeavours are, however, complicated by a lack of general methods for the routine preparation of these important compounds. Recent developments such as one-pot multistep protecting-group manipulations, the use of unified monosaccharide building blocks, the introduction of stereoselective glycosylation protocols, and convergent strategies for oligosaccharide assembly, are beginning to address these problems. Furthermore, oligosaccharide synthesis can be facilitated by chemo-enzymatic methods, which employ a range of glycosyl transferases to modify a synthetic oligosaccharide precursor. Glycosynthases, which are mutant glycosidases, that can readily form glycosidic linkages are addressing a lack of a wide range of glycosyltransferases. The power of carbohydrate chemistry is highlighted by an ability to synthesize glycoproteins.

Human milk not only has nutritional value, but also provides a wide range of biologically active molecules, which are adapted to meet the needs of newborns and infants. Mother’s milk is a source of sialylated oligosaccharides and glycans that are attached to proteins and lipids, whose concentrations and composition are unique. Sialylated human milk glycoconjugates and oligosaccharides enrich the newborn immature immune system and are crucial for their proper development and well-being. Some of the milk sialylated oligosaccharide structures can locally exert biologically active effects in the newborn’s and infant’s gut. Sialylated molecules of human milk can be recognized and bound by sialic acid-dependent pathogens and inhibit their adhesion to the epithelial cells of newborns and infants. A small amount of intact sialylated oligosaccharides can be absorbed from the intestine and remain in the newborn’s circulation in concentrations high enough to modulate the immunological system at the cellular level and facilitate proper brain development during infancy. Conclusion: The review summarizes the current state of knowledge on sialylated human milk oligosaccharides and glycoconjugates, discusses the significance of sialylated structures of human milk in newborn protection and development, and presents the advantages of human milk over infant formula.

Francisella tularensis is the causative agent of tularemia, a category A bioterrorism agent. The lipopolysaccharide (LPS) O antigen (OAg) of F. tularensis has been considered for use in a glycoconjugate vaccine, but conjugate vaccines tested so far have failed to confer protection necessary against aerosolized pulmonary bacterial challenge. When F. tularensis OAg was purified under standard conditions, the antigen had a small molecular size [25 kDa, low molecular weight (LMW)]. Using milder extraction conditions, we found the native OAg had a larger molecular size [80 kDa, high molecular weight (HMW)], and in a mouse model of tularemia, a glycoconjugate vaccine made with the HMW polysaccharide coupled to tetanus toxoid (HMW-TT) conferred better protection against intranasal challenge than a conjugate made with the LMW polysaccharide (LMW-TT). To further investigate the role of OAg size in protection, we created an F. tularensis live vaccine strain (LVS) mutant with a significantly increased OAg size [220 kDa, very high molecular weight (VHMW)] by expressing in F. tularensis a heterologous chain-length regulator gene (wzz) from the related species Francisella novicida. Immunization with VHMW-TT provided markedly increased protection over that obtained with TT glycoconjugates made using smaller OAgs. We found that protective antibodies recognize a length-dependent epitope better expressed on HMW and VHMW antigens, which bind with higher affinity to the organism.

Glycoconjugate vaccines are among the most effective interventions for preventing several serious infectious diseases. Covalent linkage of the bacterial capsular polysaccharide to a carrier protein provides CD4⁺ T cells with epitopes that facilitate a memory response to the polysaccharide. Classically, the mechanism responsible for antigen processing was thought to be similar to what was known for hapten-carrier conjugates: protease digestion of the carrier protein in the endosome and presentation of a resulting peptide to the T cell receptor on classical peptide-recognizing CD4⁺ T cells. Recently, an alternative mechanism has been shown to be responsible for the memory response to some glycoconjugates. Processing of both the protein and the polysaccharide creates glycopeptides in the endosome of antigen-presenting cells. For presentation, the peptide portion of the glycopeptide is bound to MHCII, allowing the covalently linked glycan to activate carbohydrate-specific helper CD4⁺ T cells (Tcarbs). Herein, we assessed whether this same mechanism applies to conjugates prepared from other capsular polysaccharides. All of the glycoconjugates tested induced Tcarb-dependent responses except that made with group C Neisseria meningitidis; in the latter case, only peptides generated from the carrier protein were critical for helper T cell recognition. Digestion of this acid-sensitive polysaccharide, a linear homopolymer of α(2 → 9)-linked sialic acid, to the size of the monomeric unit resulted in a dominant CD4⁺ T cell response to peptides in the context of MHCII. Our results show that different mechanisms of presentation, based on the structure of the carbohydrate, are operative in response to different glycoconjugate vaccines.

The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.

As a natural polysaccharide, chitosan possesses good biocompatibility, biodegradability and biosafety. Its hydroxyl and amino groups make it an ideal carrier material in the construction of polymer-drug conjugates. In recent years, various synthetic strategies have been used to couple chitosan with active substances to obtain conjugates with diverse structures and unique functions. In particular, chitosan conjugates with antimicrobial activity have shown great application prospects in the fields of medicine, food, and agriculture in recent years. Hence, we will place substantial emphasis on the synthetic approaches for preparing chitosan conjugates and their antimicrobial applications, which are not well summarized. Meanwhile, the challenges, limitations, and prospects of antimicrobial chitosan conjugates are described and discussed.

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.

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide–alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range. Tridecafullerenes with 120 peripheral carbohydrate groups have been made in one step from hexakis-adducts of [60]fullerene by using azide–alkyne click chemistry. This synthetic approach offers control over the size and multivalency of these ‘sugar superballs', which are shown to be potent inhibitors of cell infection by an artificial Ebola virus, with IC 50 values in the sub-nanomolar range.

Rapidly proliferating tumor cells exhibit elevated demands for nutrients and energy to support their uncontrolled growth, with glucose serving as a key metabolic substrate. Glucose is transported into cells via facilitated diffusion mediated by glucose transporters (GLUTs), after which it undergoes a series of enzymatic reactions to generate energy. To accommodate their heightened metabolic needs, cancer cells frequently overexpress GLUTs, thereby enhancing glucose uptake. Notably, aerobic glycolysis—commonly referred to as the “Warburg effect”—has been identified as the predominant pathway of glucose metabolism within tumor tissues, even in the presence of adequate oxygen levels. Consequently, the conjugation of chemotherapeutic agents, including metallodrugs, to glucose-mimicking substrates holds significant potential for achieving tumor-specific intracellular drug delivery by exploiting the elevated glucose uptake characteristic of cancer cells. Moreover, in recent years, glycosylation of metal scaffolds has been extended to the development of bioactive metallodrugs for applications other than cancer treatment, such as potential tumor imaging, antiviral, antimicrobial, antiparasitic and anti-neurodegenerative agents. Accordingly, major advancements in the design of metal-based glycoconjugates for medicinal applications are here summarized and critically discussed, focusing on related results and discoveries published subsequently to our previous (2015) review article on the topic.