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The Emerging Functionality of Endogenous Lectins: A Primer to the Concept and a Case Study on Galectins including Medical Implications

Author(s): Hans-Joachim Gabius | Albert M. Wu

Journal: Chang Gung Medical Journal
ISSN 2072-0939

Volume: 29;
Issue: 01;
Start page: 37;
Date: 2006;
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Keywords: agglutinin | apoptosis | drug design | galectin | glycoconjugate | lectin | metastasis | sugar code.

Biochemistry textbooks commonly make it appear that it is a foregoneconclusion that the hardware of biological information storage andtransfer is confined to nucleotides and amino acids, the letters of thegenetic code. However, the remarkable talents of a third class of biomoleculesare often overlooked. For example, one of them far surpasses thebuilding blocks of nucleic acids and proteins in terms of theoretical codingcapacity by oligomer formation. Although often exclusively assignedto duties in energy metabolism, carbohydrates as part of cellular glycoconjugates(glycoproteins, proteoglycans, glycolipids) have, in fact,other important tasks. Currently, they are increasingly gaining recognitionas an operative high-density information coding system. An elaborateenzymatic machinery enables cells to be versatile enough to producea glycan profile (glycome) that is as characteristic as a fingerprint.Moreover, swift modifications during dynamic processes, such as differentiationor malignant transformation, are readily possible. The translationof the information presented in oligosaccharide determinants to biologicalresponses is carried out by lectins. Recognition of foreign glycosignaturesin innate immunity, regulation of cell-cell/matrix interactions,cell migration or growth, and intra- and intercellular glycan routingetc represent physiologically far-reaching lectin-carbohydrate functionality.The classification of endogenous lectins is guided by sequencealignments and conservation of distinct structural traits. For example, ajelly-roll-like folding pattern and maintenance of key residue positioninginvolved in stacking and C-H/π-interactions as well as directional hydrogenbonds to the β-galactoside ligands are common denominators amonggalectins. Biochemical and biophysical studies are beginning to unravelthe intricacies of the selection of a limited set of endogenous ligands,such as certain integrins or ganglioside GM1, and combined with biologicalcell experiments, its relevance for cell sociology, e.g. in growth regulationand tumor cell invasion or activated T cell apoptosis. Histopathological monitoringaccompanies the biological cell investigations, linking expression of certain family membersto tumor progression or suppression. Further insights into the functional consequences of thesugar code’s translation are thus expected to have notable repercussions for diagnostic andtherapeutic procedures.
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