Glycoproteins: Structure and Function

Sharon, Nathan; Lis, Halina

doi:10.1002/9783527614738.ch8

Cited by 38 publications

(49 citation statements)

References 102 publications

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“…It is 'the most complex known chemical code in a short sequence among all biological oligomers' (Laine, 1997) and by definition predictive of a host of downstream events. They can be triggered by two principal mechanisms: (i) altering protein folding and routing as well as reactivity with ligands or other proteins, and (ii) acting as biochemical signals decoded by lectins (Sharon and Lis, 1997;Reuter and Gabius, 1999;Solís et al, 2001;Gabius et al, 2004;Honke and Taniguchi, 2009). Hereby, the fundamental functional potential of glycans is broadly realized, giving ample reason for the interest to delineate detailed structure-function relationships.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…The modification of physicochemical properties of proteins by attached carbohydrates is often observed, especially in glycoproteins with high carbohydrate content [1,7,12,13]. Sialylated or sulfated glycans, e.g., change the overall charge of a protein and increase its solubility.…”

Section: Modulation Of Physicochemical Propertiesmentioning

confidence: 99%

“…There is little doubt that the "coating" of oligosaccharides on many glycoproteins can protect the peptide backbone from recognition by proteases and antibodies [1,7,12,13]. An example is the decay accelerating factor (DAF, CD55) which is proteolyzed upon removal of its O -linked sugars [17].…”

Section: Protective and Stabilizing Functionsmentioning

confidence: 99%

Glycoproteins: Properties

Wittmann

2008

Glycoscience

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“…Glycan biosynthesis involves different types of glyco syltransferases, glycosidases and sugar nucleotides (3,4). These enzymes and corresponding substrates are often expressed in a cell-and growth-specific manner, affecting the relative amounts and structures of glycans.…”

Section: Glycosylation and Diseasementioning

confidence: 99%

Glycans as Biomarkers: Status and Perspectives

Janković¹

2011

Journal of Medical Biochemistry

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lanaca koji su kovalentno vezani za poli pep tidnu ki~mu. Dobro je poznat zna~aj prome na u glikozilaciji proteina za nastanak, razvoj i krajnji ishod razli~itih bolesti kod ljudi. Glikani se smatraju jedinstvenim strukturama za di jag nozu, i pra}enje toka bolesti. U »omics« eri, glikom, glika n ski analog proteoma i genoma, predstavlja mogu}i izvor no vih biomarkera. Kreiranje strategije za otkri}e biomarkera zahteva nove principe i platforme za analizu relativno malih koli~ina brojnih glikoproteina. O~ekuje se da glikomske teh no logije, koje su jo{ u razvoju, a koje obuhvataju razli~ite tipove masene spektrometrije i afinitivnih tehnika, rezultiraju novim analiti~kim procedurama u oblasti odre |i vanja bio markera. Najve}i izazovi za eksperimentalnu i kli ni~ku gliko pro teomiku su: pretraga razli~itih tipova gliko mo lekula, oda bir potencijalnih markera i njihova selekcija ili pre ~i{}a -vanje i identifikacija. Za ovo je neophodno razviti teh no logije koje }e omogu}iti visoku senzitivnost detekcije biomarkera kao i odgovaraju}u standardizaciju i validaciju novih metoda, kako bi se one mogle primeniti u laboratorijskom radu. Dalji razvoj na polju primenjene glikonauke zahteva integrisani sistemski pristup sa ciljem da se na pravi na~in iskoriste sve njene mo gu}nosti u dijagnostici.

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Glycoproteins: Structure and Function

Cited by 38 publications

References 102 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

Glycoproteins: Properties

Glycans as Biomarkers: Status and Perspectives

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