Lectins, a distinct group of glycan-binding proteins, play a prominent role in the immune system ranging from pathogen recognition and tuning of inflammation to cell adhesion or cellular signalling. The possibilities of their detailed study expanded along with the rapid development of biomaterials in the last decade. The immense knowledge of all aspects of glycan-lectin interactions both in vitro and in vivo may be efficiently used in bioimaging, targeted drug delivery, diagnostic and analytic biological methods. Practically applicable examples comprise photoluminescence and optical biosensors, ingenious three-dimensional carbohydrate microarrays for high-throughput screening, matrices for magnetic resonance imaging, targeted hyperthermal treatment of cancer tissues, selective inhibitors of bacterial toxins and pathogen-recognising lectin receptors, and many others. This review aims to present an up-to-date systematic overview of glycan-decorated biomaterials promising for interactions with lectins, especially those applicable in biology, biotechnology or medicine. The lectins of interest include galectin-1, -3 and -7 participating in tumour progression, bacterial lectins from Pseudomonas aeruginosa (PA-IL), E. coli (Fim-H) and Clostridium botulinum (HA33) or DC-SIGN, receptors of macrophages and dendritic cells. The spectrum of lectin-binding biomaterials covered herein ranges from glycosylated organic structures, calixarene and fullerene cores over glycopeptides and glycoproteins, functionalised carbohydrate scaffolds of cyclodextrin or chitin to self-assembling glycopolymer clusters, gels, micelles and liposomes. Glyconanoparticles, glycan arrays, and other biomaterials with a solid core are described in detail, including inorganic matrices like hydroxyapatite or stainless steel for bioimplants.
- MeSH
- Bacteria chemistry MeSH
- Biocompatible Materials chemistry standards MeSH
- Sugars chemistry MeSH
- Galectins chemistry metabolism MeSH
- Lectins, C-Type chemistry metabolism MeSH
- Lectins chemistry metabolism MeSH
- Cell Adhesion Molecules metabolism MeSH
- Receptors, Cell Surface metabolism MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biocompatible Materials MeSH
- Sugars MeSH
- DC-specific ICAM-3 grabbing nonintegrin MeSH Browser
- Galectins MeSH
- Lectins, C-Type MeSH
- Lectins MeSH
- Cell Adhesion Molecules MeSH
- Receptors, Cell Surface MeSH
Few papers have been published on tick lectins so far, and therefore more data are needed to complete the mosaic of knowledge of their structural and functional properties. Tissue-specific lectin/haemagglutinin activities of both soft and hard ticks have been investigated. Some tick lectins are proteins with binding affinity for sialic acid, various derivatives of hexosamines and different glycoconjugates. Most tick lectin/haemagglutinin activities are blood meal enhanced, and could serve as molecular factors of self/non-self recognition in defence reactions against bacteria or fungi, as well as in pathogen/parasite transmission. Dorin M, the plasma lectin of Ornithodoros moubata, is the first tick lectin purified so far from tick haemolymph, and the first that has been fully characterized. Partial characterization of other tick lectins/haemagglutinins has been performed mainly with respect to their carbohydrate binding specificities and immunochemical features.
- MeSH
- Arthropod Vectors chemistry physiology MeSH
- Gastrointestinal Tract chemistry physiology MeSH
- Hemolymph chemistry physiology MeSH
- Ticks chemistry physiology MeSH
- Lectins chemistry physiology MeSH
- Humans MeSH
- Salivary Glands chemistry physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Lectins MeSH
Carbohydrates are essential mediators of many processes in health and disease. They regulate self-/non-self- discrimination, are key elements of cellular communication, cancer, infection and inflammation, and determine protein folding, function and life-times. Moreover, they are integral to the cellular envelope for microorganisms and participate in biofilm formation. These diverse functions of carbohydrates are mediated by carbohydrate-binding proteins, lectins, and the more the knowledge about the biology of these proteins is advancing, the more interfering with carbohydrate recognition becomes a viable option for the development of novel therapeutics. In this respect, small molecules mimicking this recognition process become more and more available either as tools for fostering our basic understanding of glycobiology or as therapeutics. In this review, we outline the general design principles of glycomimetic inhibitors (Section 2). This section is then followed by highlighting three approaches to interfere with lectin function, i.e. with carbohydrate-derived glycomimetics (Section 3.1), novel glycomimetic scaffolds (Section 3.2) and allosteric modulators (Section 3.3). We summarize recent advances in design and application of glycomimetics for various classes of lectins of mammalian, viral and bacterial origin. Besides highlighting design principles in general, we showcase defined cases in which glycomimetics have been advanced to clinical trials or marketed. Additionally, emerging applications of glycomimetics for targeted protein degradation and targeted delivery purposes are reviewed in Section 4.
Lectins with a β-propeller fold bind glycans on the cell surface through multivalent binding sites and appropriate directionality. These proteins are formed by repeats of short domains, raising questions about evolutionary duplication. However, these repeats are difficult to detect in translated genomes and seldom correctly annotated in sequence databases. To address these issues, we defined the blade signature of the five types of β-propellers using 3D-structural data. With these templates, we predicted 3,887 β-propeller lectins in 1,889 species and organized this information in a searchable online database. The data reveal a widespread distribution of β-propeller lectins across species. Prediction also emphasizes multiple architectures and led to the discovery of a β-propeller assembly scenario. This was confirmed by producing and characterizing a predicted protein coded in the genome of Kordia zhangzhouensis. The crystal structure uncovers an intermediate in the evolution of β-propeller assembly and demonstrates the power of our tools.
- Keywords
- carbohydrate binding protein, lectins, oligomerization, β-propeller,
- MeSH
- Archaea chemistry MeSH
- Bacteria chemistry MeSH
- Databases, Protein MeSH
- Eukaryota chemistry MeSH
- Genome, Bacterial MeSH
- Lectins chemistry MeSH
- Models, Molecular MeSH
- Protein Multimerization MeSH
- Proteome MeSH
- Protein Folding MeSH
- Protein Structure, Secondary MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Lectins MeSH
- Proteome MeSH
Lectins and their glycosylated receptors in a system of the tick-transmitted pathogen are the addressed topics which the minireview is dealing with. They participate in the reciprocal protein-saccharide interactions in the transmission of the causative agents of the tick-borne encephalitis and Lyme borreliosis by the ticks. Functional significance of the tick tissue specific lectins as well the lectins/aggulutinis of the transmitted pathogens in molecular ecology of the tick borne diseases has been shown.
- MeSH
- Arachnid Vectors * MeSH
- Ticks * MeSH
- Encephalitis, Tick-Borne transmission MeSH
- Lectins * MeSH
- Lyme Disease transmission MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Lectins * MeSH
Vibrio cholerae (Vc) has been isolated from roots of aquatic plants during epidemic or interepidemic periods. It has been suggested that the lectins from the roots of aquatic plants play a role as reservoirs of Vc. In this paper, we evaluated the activity of lectins from Lemna minor and Eichornia crassipens plants as potential mediators of the Vc strain El Tor (Vct). We found that Lemna minor extract showed high specificity towards blood groups O and B. Eichornia crassipens extract showed high specificity towards blood group A and O. Sugar competition experiments demonstrated that Lemna minor extract showed a high recognition to Neu5Ac (acid N acetyl neuraminic or sialic acid) and GlcNAc (N-acetyl D glucoseamine) in group B; and GlcNAc in group O. Eichornia crassipens, the recognition was that of GalNAc (N-acetyl-D-galactoseamine) and GlcNAc in group O; and Fuc (L-Fucose) and GlcNAc in group A. Lemna minor and Eichornia crassipens protein extracts (p-ext) increased Vct proliferation and protected to the red cells group O against the hemolytic activity of Vct. Both p-exts did not show any statistical significance on agglutination to Vct when compared to the results from phosphate buffer. According to the results, lectins present in roots may be involved in the proliferation and survival of Vct.
- Keywords
- Vibrio cholera - Lemna minor - Eichornia crassipens - lectins.,
- MeSH
- Araceae chemistry MeSH
- Bacterial Adhesion * physiology MeSH
- Eichhornia chemistry MeSH
- Lectins * metabolism MeSH
- Vibrio cholerae * MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lectins * MeSH
The interactions of fish trypanosome culture forms with 11 purified lectins were compared using the agglutination test in microwell plates. Altogether, ten stocks of ten different freshwater fish species were examined. Three basic types of cell-lectin interactions were observed on the microscopical level. The strong agglutination of all stocks regardless their original host was found in the presence of Con A, PSA, RCA60, and RCA120, which implies the presence of relatively high amounts of sugar residues of D-mannose and D-galactose in the surface of culture forms of these parasites. Weak agglutinations of some stocks were observed in the presence of LCA, PNA, SBA, and WGA lectins, but their low intensity makes them not sufficiently reliable for stock characterization. The lectins UEA I, HPA, and PHA caused no agglutination. In conclusion, in case of unequivocal results no remarkable differences in the interactions of various stocks of trypanosomes culture forms with used lectins were observed. These results imply the high degree of similarity of their main cell surface saccharide structures.
- MeSH
- Agglutination Tests MeSH
- Lectins metabolism MeSH
- Fish Diseases parasitology MeSH
- Fishes MeSH
- Fresh Water MeSH
- Trypanosoma metabolism MeSH
- Trypanosomiasis parasitology veterinary MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lectins MeSH
The review is devoted to the gut lectins/hemagglutinins of the following representatives of important disease vectors: ticks, kissing-bugs, mosquitoes, sandflies and tsetse flies. The paper surveys the recent knowledge on these carbohydrate binding factors with respect to their structural and functional properties, and their significance for pathogen/parasite transmission by the blood-sucking arthropods. Recent results suggest that in most vectors the gut lectin activities are blood-meal enhanced, might participate in blood-meal processing and digestion and could serve as antibacterial and antiparasitic agents.
- MeSH
- Arthropod Vectors MeSH
- Insect Vectors MeSH
- Disease Vectors * MeSH
- Lectins analysis MeSH
- Intestines chemistry MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Lectins MeSH
Pseudomonas aeruginosa is a prevalent opportunistic human pathogen, particularly associated with cystic fibrosis. Among its virulence factors are the LecA and LecB lectins. Both lectins play an important role in the adhesion to the host cells and display cytotoxic activity. In this study, we successfully synthesized hardly hydrolysable carbohydrate ligands targeting these pathogenic lectins, including two bispecific glycans. The interactions between LecA/LecB lectins and synthetic glycans were evaluated using hemagglutination (yeast agglutination) inhibition assays, comparing their efficacy with corresponding monosaccharides. Additionally, the binding affinities of bispecific glycans were assessed using isothermal titration calorimetry (ITC). Structural insight into the lectin-ligand interaction was obtained by determining the crystal structures of LecA/LecB lectins in complex with one of the bispecific ligands using X ray crystallography. This comprehensive investigation into the inhibitory potential of synthetic glycosides against P. aeruginosa lectins sheds light on their potential application in antimicrobial therapy.
- Keywords
- Agglutination, Inhibition, Lectins, Pseudomonas aeruginosa, Synthetic carbohydrates,
- MeSH
- Adhesins, Bacterial * chemistry metabolism MeSH
- Disaccharides * chemistry pharmacology MeSH
- Crystallography, X-Ray MeSH
- Lectins * chemistry antagonists & inhibitors metabolism MeSH
- Humans MeSH
- Ligands MeSH
- Polysaccharides chemistry MeSH
- Pseudomonas aeruginosa * chemistry metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adhesins, Bacterial * MeSH
- Disaccharides * MeSH
- LecA protein, bacteria MeSH Browser
- LecB protein, Pseudomonas aeruginosa MeSH Browser
- Lectins * MeSH
- Ligands MeSH
- Polysaccharides MeSH
Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, α-l-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of Pseudomonas aeruginosa cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras.
- Keywords
- cystic fibrosis, glycoclusters, hemagglutination, l-fucosides, lectins, multivalency,
- MeSH
- Bacterial Proteins chemistry metabolism MeSH
- Fucose chemistry metabolism MeSH
- Fungal Proteins chemistry metabolism MeSH
- Hemagglutination MeSH
- Lectins chemistry metabolism MeSH
- Humans MeSH
- Hemagglutination Inhibition Tests MeSH
- Protein Binding MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bacterial Proteins MeSH
- fucose-binding lectin MeSH Browser
- Fucose MeSH
- Fungal Proteins MeSH
- Lectins MeSH
