Polyvalency of glycotopes and their conformational features in glycans as the most powerful recognition factors for the glycan-lectin interactions

Glycans (Carbohydrates) are one of the three major classes of biological macromolecules, all of which encode information essential for the life of an organism. Lectins are Glycan Binding Proteins (GBP). On cell surfaces, they mediate cell-cell interactions by combining with complementary carbohydrates on opposing cells, in which lectin-glycan interactions play a key role in the control of various normal and pathological processes in living organisms, such as fertilization, embryogenesis, cell migration, organ formation, immune defense, and microbial infection. At the present time, no one knows how many Recognitions Factors (RFs) are involved in lectin-glycan interactions in nature. During the past 70 years, six of them have been adopted and identified. They are: (i) submonosaccharide specificity: epimers and anomers of a sugar; (ii) Monosaccharide specificity: Gal, GalNAc, GlcNAc, Man, LFuc, and NeuNAc from mammalians; (iii) Reactivities toward mammalian di(oligo)-saccharides and Tn glycotope in a decreasing order; (iv) The most active ligand (= Glycotope) among the structural units; (v) Simple multivalent or cluster form of carbohydrate structural units, Tn glycopeptides and multiantennary glycotopes; (vi) Complex polyvalent structural units/glycotopes present in macromolecules. Among them, monomeric RFs (ii-iv) are the weak ones, but they are the essential elements (similar to amino acids in proteins) for binding. They have been used to classify the (applied) lectins. Polyvalency of glycotopes and their conformational features is the critical factor (v to vi) for the mechanism of glycan-lectin interactions. The resulting enhancement can be up to 1.0x106 or more potent than their monomers. Since early 1980s, polyvalent glycotopes in glycans as the most powerful recognition factor, as illustrated in this review, should be one of the most valuable achievements in the field of glycoscience. It is also one of the important directions toward future transformation. This review is dedicated to Drs. Elwira Lisowska and Maria Duk (Department of Immunochemistry, Ludwik Hiszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.), for their valuable contributions to the development of ELLSA.