The Relevance of Neoglycoconjugates for Histology and Pathology.

Danguy, André; Kayser, Klaus; Bovin, Nicolai V.; Gabius, Hans‐Joachim; 義弘, 秋元; 寛, 平野

doi:10.4052/tigg.7.261

Cited by 36 publications

(25 citation statements)

References 9 publications

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“…If pure glycans were available, this issue could be resolved. In that case, their chemical attachment to a carrier protein will produce the equivalent of natural glycoproteins, a neoglycoprotein, with custom-made ligand part for lectin interaction (Gabius et al, 1988(Gabius et al, , 1993Danguy et al, 1994Danguy et al, , 1995Lee and Lee, 1994;Legendre et al, 2004). Toward this end, chemoenzymatic N-glycan synthesis and conjugation to serum albumin as standard carrier was performed in all cases.…”

Section: Will Core Substitutions Shift Conformational Equilibria In Nmentioning

confidence: 99%

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

André

Kožár²,

Kojima³

et al. 2009

BCHM

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Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals (sugar coding). Here, we test the hypothesis that the common N-glycan modifications by core fucosylation and introduction of the bisecting Nacetylglucosamine moiety have long-range effects with functional consequences. Molecular dynamics simulations indicate a shift in conformational equilibria between linear extension or backfolding of the glycan antennae upon substitution. We also present a new fingerprint-like mode of presentation for this multi-parameter system. In order to delineate definite structure-function relationships, we strategically combined chemoenzymatic synthesis with bioassaying cell binding and the distribution of radioiodinated neoglycoproteins in vivo. Of clinical relevance, tailoring the core region affects serum clearance markedly, e.g., prolonging circulation time for the neoglycoprotein presenting the N-glycan with both substitutions. a2,3-Sialylation is another means toward this end, similarly seen for type II branching in triantennary N-glycans. This discovery signifies that rational glycoengineering along the given lines is an attractive perspective to optimize pharmacokinetic behavior of glycosylated pharmaproteins. Of general importance for the concept of the sugar code, the presented results teach the fundamental lesson that N-glycan core substitutions convey distinct characteristics to the concerned oligosaccharide relevant for cis and trans biorecognition processes. These modifications are thus molecular switches.

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Section: Will Core Substitutions Shift Conformational Equilibria In Nmentioning

confidence: 99%

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

André

Kožár²,

Kojima³

et al. 2009

BCHM

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“…Focusing on glycobiology, the feasibility of chemical design of neoglycoconjugates has already engendered considerable efforts . They have enabled to accrue complementary information to conventional lectin histochemistry by the exploitation of neoglycoconjugates, termed 'reverse lectin histochemistry' [Gabius et al, 1993;Danguy et al, 1994Danguy et al, , 1995. In view of the ample documentation of lectin expression in animal tissues, to which this technique contributes remarkably, it is no longer appropriate to consider the area of lectinology as a bashful search for any tenuous thread of evidence for a physiological relevance.…”

Section: Resultsmentioning

confidence: 99%

“…Only immobilization to a histochemically inert carrier backbone is required to yield a histochemical marker. Unless the receptor's activity is blocked or impaired by tissue processing and the ligand's interaction potential is diminished by derivation, such 'neoligandoconjugates' can find a broad range of applications [Gabius and Bardosi, 1991;Kayser et al, 1991;Danguy et al, 1995;Kayser and Gabius, 1997]. Focusing on glycobiology, the feasibility of chemical design of neoglycoconjugates has already engendered considerable efforts .…”

Section: Resultsmentioning

confidence: 99%

Lectin Ligands: New Insights into Their Conformations and Their Dynamic Behavior and the Discovery of Conformer Selection by Lectins

Lieth

Siebert

Kožár³

et al. 1998

Cells Tissues Organs

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The mysteries of the functions of complex glycoconjugates have enthralled scientists over decades. Theoretical considerations have ascribed an enormous capacity to store information to oligosaccharides. In the interplay with lectins sugar-code words of complex carbohydrate structures can be deciphered. To capitalize on knowledge about this type of molecular recognition for rational marker/drug design, the intimate details of the recognition process must be delineated. To this aim the required approach is garnered from several fields, profiting from advances primarily in X-ray crystallography, nuclear magnetic resonance spectroscopy and computational calculations encompassing molecular mechanics, molecular dynamics and homology modeling. Collectively considered, the results force us to jettison the preconception of a rigid ligand structure. On the contrary, a carbohydrate ligand may move rather freely between two or even more low-energy positions, affording the basis for conformer selection by a lectin. By an exemplary illustration of the interdisciplinary approach including up-to-date refinements in carbohydrate modeling it is underscored why this combination is considered to show promise of fostering innovative strategies in rational marker/drug design.

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“…The bound probes were visualized with a fresh solution of diaminobenzidinetetrahydrochloride (DAB) and hydrogen peroxide-DAB polymers are insoluble in organic solvents and are stable, providing a permanent record, when slides are stored. Readers are advised to consult articles Danguy, 1995;Danguy et al, 1995Danguy et al, , 1997, histochemical books [Polak and Van Noorden, 1983;DeLellis, 1988;Kiernan, 1990] and catalogues of commercial suppliers for further details of the methodologies.…”

Section: Modern Glycohistochemistrymentioning

confidence: 99%

Applications of Lectins and Neoglycoconjugates in Histology and Pathology

Danguy¹,

Decaestecker²,

Genten

et al. 1998

Cells Tissues Organs

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The biological importance of oligosaccharide sequences in many different settings is undeniable. Glycan histochemistry has brought together the histological and biochemical approaches and provided insight into the mutual importance of both approaches. The aim of the authors is to take a look at a number of ways in which modern glycohistochemistry contributes to acquiring knowledge about the key role played by carbohydrates in the physiology of vertebrate tissues and human disease. The versatility of lectin and neoglycoconjugate histochemical procedures is emphasized.

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The Relevance of Neoglycoconjugates for Histology and Pathology.

Abstract: 'g•DŠw ‹y ‚Ñ•a-• Šw‚É‚¨‚¯Šw‚É‚¨‚¯ ‚é ƒl ƒI•¡ • ‡"oeŽ¿‚Ì "K-p 1 Danguy, A.; 2Kayser, K.; 3Bovin, N.

Cited by 36 publications

References 9 publications

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

Lectin Ligands: New Insights into Their Conformations and Their Dynamic Behavior and the Discovery of Conformer Selection by Lectins

Applications of Lectins and Neoglycoconjugates in Histology and Pathology

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