The Third Dimension of Reading the Sugar Code by Lectins: Design of Glycoclusters with Cyclic Scaffolds as Tools with the Aim to Define Correlations between Spatial Presentation and Activity
Open Access
- 4 April 2013
- Vol. 18 (4), 4026-4053
- https://doi.org/10.3390/molecules18044026
Abstract
Coding of biological information is not confined to nucleic acids and proteins. Endowed with the highest level of structural versatility among biomolecules, the glycan chains of cellular glycoconjugates are well-suited to generate molecular messages/signals in a minimum of space. The sequence and shape of oligosaccharides as well as spatial aspects of multivalent presentation are assumed to underlie the natural specificity/selectivity that cellular glycans have for endogenous lectins. In order to eventually unravel structure-activity profiles cyclic scaffolds have been used as platforms to produce glycoclusters and afford valuable tools. Using adhesion/growth-regulatory galectins and the pan-galectin ligand lactose as a model, emerging insights into the potential of cyclodextrins, cyclic peptides, calixarenes and glycophanes for this purpose are presented herein. The systematic testing of lectin panels with spatially defined ligand presentations can be considered as a biomimetic means to help clarify the mechanisms, which lead to the exquisite accuracy at which endogenous lectins select their physiological counterreceptors from the complexity of the cellular glycome.This publication has 134 references indexed in Scilit:
- Why nature chose phosphate to modify proteinsPhilosophical Transactions B, 2012
- Modifications of Glycans: Biological Significance and Therapeutic OpportunitiesACS Chemical Biology, 2011
- Ganglioside GM1 Deficiency in Effector T Cells From NOD Mice Induces Resistance to Regulatory T-Cell SuppressionDiabetes, 2011
- Structural aspects of binding of α-linked digalactosides to human galectin-1Glycobiology, 2011
- Carbohydrate analysis throughout the development of a protein therapeuticGlycoconjugate Journal, 2009
- Dimeric Galectin-8 Induces Phosphatidylserine Exposure in Leukocytes through Polylactosamine Recognition by the C-terminal DomainJournal of Biological Chemistry, 2008
- Multivalent Interactions between Lectins and Supramolecular Complexes: Galectin-1 and Self-Assembled PseudopolyrotaxanesCell Chemical Biology, 2007
- Growth-regulatory Human Galectin-1: Crystallographic Characterisation of the Structural Changes Induced by Single-site Mutations and their Impact on the Thermodynamics of Ligand BindingJournal of Molecular Biology, 2004
- The Chemistry of Isocyanides, their MultiComponent Reactions and their LibrariesMolecules, 2003
- Correlation of expression of binding sites for synthetic blood group A-, B- and H- trisaccharides and for sarcolectin with survival of patients with bronchial carcinomaEuropean Journal of Cancer, 1994