Biologia 64/1: 1—19, 2009 Section Cellular and Molecular Biology DOI: 10.2478/s11756-009-0029-3 Review Lectinomics I. Relevance of exogenous plant lectins in biomedical diagnostics Danica Mislovičová 1 , Peter Gemeiner 1 , Anna Kozarova 2 & Tibor Kožár 3 1 Department of Glycobiotechnology, Center for Glycomics, Institute of Chemistry, Slovak Academy of Science, Dúbravská cesta 9, SK-84538 Bratislava, Slovakia; e-mail: chemmisl@savba.sk 2 Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada 3 Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, SK-04541 Košice, Slovakia Abstract: This review focuses on utilization of plant lectins as medical diagnostic reagents and tools. The lectin-related diagnostic is aimed at detection of several diseases connected to alteration of the glycosylation profiles of cells and at identification of microbial and viral agents in clinical microbiology. Certain lectins, proposed for or used as diagnostic tools could even recognize those cellular determinants, which are not detected by available antibodies. Broad information is presented on the lectinomics field, illustrating that lectin diagnostics might become practical alternative to antibody-based diagnostic products. In addition, the rising trend of lectin utilization in biomedical diagnostics might initiate a development of innovative methods based on better analytical technologies. Lectin microarray, a rapid and simple methodology, can be viewed as an example for such initiative. This technology could provide simple and efficient screening tools for analysis of glycosylation patterns in biological samples (cellular extracts, tissues and the whole cells), allowing thus personalized detection of changes associated with carbohydrate-related diseases. Key words: plant lectins; diagnostic tool; alteration of glycosylation; saccharide specificity; biomedical application. Abbreviations: AFP, human α-fetoprotein; AsAGP, asialo-α1 -acid glycoprotein; BPH, benign prostatic hyperplasia; CAIE, crossed-affino-immunoelectrophoresis; CNS, coagulase-negative staphylococci; ELISA, enzyme-linked immunoassay; ELLA, enzyme-linked lectin assay; FHp, fucosylated haptoglobin; FITC, fluorescein isothiocyanate; GPA, glycophorin A; HCC, hepatocellular carcinoma; hCG, human chorionic gonatropin; hESC, human embryonic stem cells; HIV, human im- munodeficiency virus; HSV, herpes simplex virus; LAC, lectin affinity chromatography; MS, mass spectrometry; MDCK, Madin Darby canine kidney; MDR, multidrug resistance; PCA, prostatic cancer; Pgp, P-glycoprotein; PSa, prostate specific antigen; SCC, squamous cell carcinoma; SPR, surface plasmon resonance. For the abbreviations of lectins, see Table 1. Introduction Carbohydrates, in forms of glycoproteins, glycolipids and polysaccharides are important signaling molecules. Sugar-based modifications are not only found on cell surface (as for example the blood cells and viral HIV glycans), but also present on most plasma membrane and secretory proteins. Carbohydrates have great po- tential to encode biological information and may there- fore act as recognition determinants in a variety of physiological and pathological processes (Sharon & Lis 1993). Glycans, as potential biomarkers for several diseases, caught attention also in clinical proteomics (Wuhrer 2007). Not surprisingly, aberrant glycosylation is observed in a variety of diseased conditions (Varki, 1999), including hereditary disorders (Durand & Seta 2000), cancer (Dennis et al. 1999; Dube & Bertozzi 2005; Fuster & Esko 2005), immunodeficiency (Ji et al. 2006), neurodegeneration and diabetes (Hart et al. 2007). Experimental approaches have been developed for biochemical analysis of patient samples; these are either based on measurements of changes in activity lev- els of enzymes responsible for particular glycan synthe- sis and/or the alterations in cell-surface oligosaccharide structures (Durand & Seta 2000; Schulz et al. 2007). Lectins are proteins that specifically bind car- bohydrates, of either mono- or oligosaccharide struc- tures. Examples of lectin’s high specificity for gly- can ligands include prototypical plant lectins like con- canavalin A (Con A) which recognizes mannose and glucose (Man/Glc), wheat germ agglutinin (WGA) that recognizes N-acetylglucosamine (GlcNAc) and N- acetylneuraminic acid (Neu5Ac), soybean agglutinin (SBA) specific for galactose (Gal) and N-acetylgalac- tosamine (GalNAc), and ricin (RCA) that recognize Gal (Fig. 1). While some highly conserved amino acid residues present in the binding site provide the basis for carbohydrate-lectin interactions, the specificity of binding is proposed to arise from a variability of amino acids within the other regions of carbohydrate-binding site (Ambrosi et al. 2005). Furthermore, the association constants of lectins for di-, tri- and tetrasaccharides are significantly higher than for corresponding monosaccha- rides (Ambrosi et al. 2005). Comprehensive information c 2009 Institute of Molecular Biology, Slovak Academy of Sciences