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1. (Article ID: 8005)
 
Zhang Y, Yamaguchi T, Kato K
New NMR tools for characterizing the dynamic conformations and interactions of oligosaccharides
Chemistry Letters 42(12) (2013) 1455-1462
 

Oligosaccharides play pivotal roles in various molecular recognition events on cell surfaces and in intracellular environments. Although information about the three-dimensional structure of oligosaccharides is crucial for understanding the mechanisms underlying their biological functions and for designing drugs targeting carbohydrate recognition systems, their inherent flexibility hampers detailed conformational analysis. NMR spectroscopy has immense potential for providing atomic details of oligosaccharide structures in solution as well as in complexes with other biomolecules. However, the traditional NMR approach based on local conformational information provided by the nuclear Overhauser effect (NOE) is often precluded by insufficient information about long interatomic distances and hydrogen bonds involving hydroxy groups. To address these issues, new NMR techniques have recently been developed, exploiting the effects of introduced paramagnetic probes and stable isotopes to target oligosaccharides. Lanthanoid tagging and the spin labeling of oligosaccharides induce paramagnetic effects such as pseudocontact shift and paramagnetic relaxation enhancement, offering NOEindependent sources of long-distance information. Deuteriuminduced isotope shifts of neighboring 13C resonances provide an experimental tool for the identification of hydrogen bonds involving oligosaccharide hydroxy groups. The uniform and position-selective 13C enrichment of oligosaccharides can be achieved by metabolic labeling using genetically engineered yeast cells. Furthermore, small ganglioside-embedding bicelles have been used for detailed NMR analyses of intermolecular interactions involving glycolipids in membrane environments. These NMR approaches, in conjunction with computational simulation, have opened up new vistas for the analysis of oligosaccharide conformations and interactions at atomic level. fate determination, intercellular communication, and viral infections.1 The detailed characterization of the 3D structures of oligosaccharides in both free and bound states is crucial for understanding their underlying functions and mechanisms and for providing insights into recognition mechanisms that are useful in the design of carbohydrate-based drugs.2,3 Compared to protein structural biology, 3D-structural study of oligosaccharides is still immature, primarily because of high inherent flexibility. The many degrees of freedom in internal motion exhibited by oligosaccharides endow them with conformational adaptability in interacting with various target biomolecules.2,4 This makes the structural analysis of carbohydrates by traditional techniques such as crystallography difficult. NMR is almost the only tool for providing atomic-resolution pictures of oligosaccharides in solution.5 Although NMR spectroscopy has immense potential for providing information about the conformational dynamics of biomolecules, the NOEbased approach, widely used for protein structure determination, is often limited by insufficient distance-restraint information due t the low density of observable protons in oligosaccharides. Hence, NOE-independent approaches would be valuable for the determination of oligosaccharide conformations and dynamics. Another major problem in the NMR analysis of oligosaccharide is severe signal overlap, which hampers unambiguous resonance assignment even at high magnetic fields. Unlike proteins for which systematic methods for selective and uniform labeling are available for heteronuclear NMR analysis, the preparation of isotopically labeled oligosaccharides is still tricky and complicated. In addition, oligosaccharides interact with various targetmolecules, typically forming dynamic hydrogen-bonding networks with their hydroxy functionalities. Such intermolecular hydrogen-bond bridges are major factors that determine affinity and specificity in carbohydratecarbohydrate and carbohydrateprotein interactions. However, it is difficult to characterize such hydrogen-bonding networks in oligosaccharide complexes by the measurement of intermolecular NOE between nonexchangeable protons. Hence, new NMR techniques are required to capture the detailed information of oligosaccharideoligosaccharide and oligosaccharideprotein interactions, especially for the development of drugs targeting carbohydrate recognition systems.

NMR, dynamic conformations

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