Analysis of Protein–Carbohydrate Interaction Using Engineered Ligands

Solı́s, Dolores; Dı́az-Mauriño, Teresa

doi:10.1002/9783527614738.ch19

Cited by 6 publications

(8 citation statements)

References 55 publications

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“…It can thus be expected that the axial 4′-position for recognition of d-Gal and the equatorial 3′,4′-positions for binding d-Man/d-Glc play decisive roles. This assumption is strikingly verified by x-ray crystallography and in solution by chemically engineered ligand derivatives (Rini, 1995;Solís et al, 1996;Weis and Drickamer, 1996;Gabius, 1997a, Solís andDíaz-Mauriño, 1997;Gabius, 1998;Lis and Sharon, 1998;Loris et al, 1998;Rüdiger et al, 1999;). With this structural explanation it becomes obvious why the change of the position of one hydroxyl group to form an epimer discussed during the presentation of the individual members of the monosaccharide alphabet unmistakably has the effect of creating a new letter.…”

Section: How To Define Potent Ligand Mimeticsmentioning

confidence: 67%

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Gabius

2008

Biosemiotics

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In the era of genetic engineering, cloning, and genome sequencing, the focus of research on the genetic code has received an even further accentuation in the public eye. When, however, aspiring to understand intra-and intercellular recognition processes comprehensively, the two biochemical dimensions established by nucleic acids and proteins are not sufficient to satisfactorily explain all molecular events in, e.g. cell adhesion or routing. To bridge this gap consideration of further code systems is essential. A third biochemical alphabet forming code words with an information storage capacity second to no other substance class in rather small units (words, sentences) is established by monosaccharides (letters). As hardware oligosaccharides surpass peptides by more than seven orders of magnitude in the theoretical ability to build isomers, then the total of conceivable hexamers is calculated. Beyond the sequence complexity application of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling have been instrumental to discover that even small glycans can often reside in not only one but several distinct low-energy conformations (keys). Intriguingly, conformers can display notably different capacities to fit snugly into the binding site of nonhomologous receptors (locks). This process, experimentally verified for two classes of lectins, is termed "differential conformer selection." It adds potential for shifts of the conformer equilibrium to modulate ligand properties dynamically and reversibly to the wellknown changes of sequence (including anomeric positioning and linkage points) and of pattern of substitution, e.g. by sulfation. In the intimate interplay with sugar receptors (lectins, enzymes, and antibodies) the message of coding units of the sugar code is deciphered. This communication will trigger postbinding signaling and the intended biological response. Knowledge about the driving forces for the molecular rendezvous, that is, contributions of bidentate or cooperative hydrogen bonds, dispersion forces, stacking and solvent rearrangement, will enable the design * Reprinted with permission from Naturwissenschaften, Vol. 87 (2000), pp. 108-121. Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539 München, Germany, e-mail: gabius@tiph.vetmed.uni-muenchen

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Section: How To Define Potent Ligand Mimeticsmentioning

confidence: 67%

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Gabius

2008

Biosemiotics

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“…The tolerance of ·2,3-sialylation by galectins explains their binding to poly-N-acetyllactosamine chains (Galß1,4GlcNAcß1,3 units) and possibly also to internal sites, for example presented by the ganglioside GM 1 , a major galectin ligand on human neuroblastoma cells [Gabius, 1997a;Kopitz et al, 1998;André et al, 1999b]. With respect to the mentioned influence of the often nonphysiological conditions for crystallization it is notable that a thorough comparison of ricin's mode of ligand binding by crystallographic analysis and chemical mapping intimates a difference attributed to the pH in the crystallization protocol [Solís et al, 1993;Solís and Díaz-Mauriño, 1997]. These examples allow to insinuate that exploitation of engineered ligands is a great asset for mapping the hydrogen-bonding pattern with implications for drug design [Solís and Díaz-Mauriño, 1997;Rüdiger et al, 2000].…”

Section: How Lectins and Carbohydrate Ligands Interactmentioning

confidence: 99%

“…With respect to the mentioned influence of the often nonphysiological conditions for crystallization it is notable that a thorough comparison of ricin's mode of ligand binding by crystallographic analysis and chemical mapping intimates a difference attributed to the pH in the crystallization protocol [Solís et al, 1993;Solís and Díaz-Mauriño, 1997]. These examples allow to insinuate that exploitation of engineered ligands is a great asset for mapping the hydrogen-bonding pattern with implications for drug design [Solís and Díaz-Mauriño, 1997;Rüdiger et al, 2000]. As similarly added to the section on crystal-lography, voicing sources of potential complications is nonetheless essential to avoid to be led astray in special instances.…”

Section: How Lectins and Carbohydrate Ligands Interactmentioning

confidence: 99%

“…Any hydroxyl group can be chosen as target for site-specific modification, and the binding properties of the derivatives can be assessed in relation to the natural ligand [Lemieux, 1989;Solís and Díaz-Mauriño, 1997]. The types of chemical replacements and their expectable impacts on the regular donor-acceptor profile of hydroxyl groups are compiled in figure 12.…”

Section: How Lectins and Carbohydrate Ligands Interactmentioning

confidence: 99%

“…5) establish the concept of differential conformer selection by lectins [Siebert et al, 1996;Poppe et al, 1997;Gilleron et al, 1998;von der Lieth et al, 1998;Harris et al, 1999]. Not only different sections of functional groups of a carbohydrate ligand are relevant for binding, as documented for example for plant, animal and bacterial galactoside-or plant blood group H (type 2)-trisaccharide-binding lectins by chemical mapping [Rivera-Sagredo et al, 1991;Du et al, 1994;Haataja et al, 1994;Solís et al, 1994;Solís and Díaz-Mauriño, 1997]. Importantly, each of the conformations in solution can be selected by different receptors as bioactive.…”

Section: How Lectins and Carbohydrate Ligands Interactmentioning

confidence: 99%

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Towards Defining the Role of Glycans as Hardware in Information Storage and Transfer: Basic Principles, Experimental Approaches and Recent Progress

Solı́s¹,

Jiménez‐Barbero²,

Kaltner³

et al. 2000

Cells Tissues Organs

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The term ‘code’ in biological information transfer appears to be tightly and hitherto exclusively connected with the genetic code based on nucleotides and translated into functional activities via proteins. However, the recent appreciation of the enormous coding capacity of oligosaccharide chains of natural glycoconjugates has spurred to give heed to a new concept: versatile glycan assembly by the genetically encoded glycosyltransferases endows cells with a probably not yet fully catalogued array of meaningful messages. Enciphered by sugar receptors such as endogenous lectins the information of code words established by a series of covalently linked monosaccharides as letters for example guides correct intra- and intercellular routing of glycoproteins, modulates cell proliferation or migration and mediates cell adhesion. Evidently, the elucidation of the structural frameworks and the recognition strategies within the operation of the sugar code poses a fascinating conundrum. The far-reaching impact of this recognition mode on the level of cells, tissues and organs has fueled vigorous investigations to probe the subtleties of protein-carbohydrate interactions. This review presents information on the necessarily concerted approach using X-ray crystallography, molecular modeling, nuclear magnetic resonance spectroscopy, thermodynamic analysis and engineered ligands and receptors. This part of the treatise is flanked by exemplarily chosen insights made possible by these techniques.

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The Codes of Life

Barbieri¹,

Hoffmeyer²

2008

Biosemiotics

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Aims and Scope of the SeriesCombining research approaches from biology, philosophy and linguistics, the emerging field of biosemiotics proposes that animals, plants and single cells all engage in semiosis -the conversion of physical signals into conventional signs. This has important implications and applications for issues ranging from natural selection to animal behaviour and human psychology, leaving biosemiotics at the cutting edge of the research on the fundamentals of life.The Springer book series Biosemiotics draws together contributions from leading players in international biosemiotics, producing an unparalleled series that will appeal to all those interested in the origins and evolution of life, including molecular and evolutionary biologists, ecologists, anthropologists, psychologists, philosophers and historians of science, linguists, semioticians and researchers in artificial life, information theory and communication technology.

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Analysis of Protein–Carbohydrate Interaction Using Engineered Ligands

Cited by 6 publications

References 55 publications

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Towards Defining the Role of Glycans as Hardware in Information Storage and Transfer: Basic Principles, Experimental Approaches and Recent Progress

The Codes of Life

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