Glycobiology:  Toward Understanding the Function of Sugars

Dwek, Raymond A.

doi:10.1021/cr940283b

Cited by 2,860 publications

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“…The combinations of N-glycan and protein, and N-glycan bound protein may be crucial for their functions (26,27). It is more likely that altered N-glycans associated with several different proteins affect the drug-resistance mechanisms.…”

Section: Figmentioning

confidence: 99%

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Functional roles of glycogene and N‐glycan in multidrug resistance of human breast cancer cells

Xing

et al. 2013

IUBMB Life

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Drug resistance is a major problem in cancer chemotherapy. Aberrant glycosylation has been known to be associated with cancer chemoresistance. Aim of this work is to investigate the alterations of glycogene and N-glycan involved in multidrug resistance (MDR) in human breast cancer cell lines. Using real-time polymerase chain reaction (PCR) for quantification of glycogenes, fluorescein isothiocyanate (FITC)-lectin binding for glycan profiling, and mass spectrometry for N-glycan composition, the expression of glycogenes, glycan profiling, and N-glycan composition differed between drug-resistant MCF/ ADR cells and the parental MCF-7 line. Further analysis of the N-glycan regulation by tunicamycin (TM) application or PNGase F treatment in MCF/ADR cells showed partial inhibition of the N-glycan biosynthesis and increased sensitivity to chemotherapeutic drugs dramatically both in vitro and in vivo. Using an RNA interference strategy, we showed that the downregulation of MGAT5 in MCF/ADR cells could enhance the chemosensitivity to antitumor drugs both in vitro and in vivo. Conversely, a stable high expression of MGAT5 in MCF-7 cells could increase resistance to chemotherapeutic drugs both in vitro and in vivo. In conclusion, the alterations of glycogene and N-glycan in human breast cancer cells correlate with tumor sensitivity to chemotherapeutic drug and have significant implications for the development of new treatment strategies. V C 2013 IUBMB Life, 65(5): 409-422, 2013.

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Section: Figmentioning

confidence: 99%

“…N-glycosylation of protein is increasingly being recognized as one of the most prominent biochemical alterations involved in tumorigenesis and metastasis (2,3). Both changes in the core structures and increased branching of N-linked oligosaccharides are associated with malignancy and metastasis (4).…”

Section: Introductionmentioning

confidence: 99%

Functional roles of glycogene and N‐glycan in multidrug resistance of human breast cancer cells

Xing

et al. 2013

IUBMB Life

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“…and human disease states (e.g., cancer; congenital disorders of glycosylation; neurodegenerative disorders, etc.). [6][7][8][9][10][11][12][13][14][15][16][17] While protein glycosylation analyses are oen carried out with either a "glycocentric" (i.e., compositional and structural analysis of glycans released from glycoproteins) or a "proteocentric" (i.e., identication of deglycosylated glycoproteins with indirect glycosylation site localization) outlook, the loss of molecular detail imposed by glycan release limits the specicity and potential for biological resolution that can be furnished by such analyses. 18 In order to map specic oligosaccharide structures to their corresponding sites of protein attachment, the analytical scheme must preserve the oligosaccharide-polypeptide connectivity until such a time that the chosen approach can characterize the linkage.…”

Section: Introductionmentioning

confidence: 99%

Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment

Kolli

Dodds

2014

Analyst

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"Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment" (2014). Faculty Publications --Chemistry Department. 68. http://digitalcommons.unl.edu/chemfacpub/68Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment † Venkata Kolli and Eric D. Dodds * Tandem mass spectrometry (MS/MS) of glycopeptides stands among the principal analytical approaches for assessing protein glycosylation in a site-specific manner. The aims of such experiments are often to determine the monosaccharide connectivity of the glycan, the amino acid sequence of the peptide, and the site of glycan attachment. This level of detail is often difficult to achieve using any single ion dissociation method; however, precedent does exist for use of collision-induced dissociation (CID) to establish either the connectivity of the oligosaccharide or the sequence of the polypeptide depending upon the applied collision energy. Unfortunately, the relative energy requirements for glycan and peptide cleavage have not been thoroughly characterized with respect to specific physicochemical characteristics of the precursor ions. This report describes case studies on the energy-resolved CID pathways of model tryptic glycopeptides derived from Erythrina cristagalli lectin and bovine ribonuclease B. While glycopeptide ions having disparate physical and chemical characteristics shared strikingly similar qualitative responses to increasing vibrational energy deposition, the absolute collision energies at which either glycan or peptide fragmentations were accessed varied substantially among the precursor ions examined. Nevertheless, these data suggest that the energy requirements for peptide and glycan cleavage may be somewhat predictable based on characteristics of the precursor ion. The practical usefulness of these observations was demonstrated through implementation of online collision energy modulation such that both glycan and peptide fragmentation were captured in the same spectrum, providing near-exhaustive glycopeptide characterization in a single experiment. Overall, these results highlight the potential to further extend the capabilities of CID in the context of glycoproteomics.

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“…G lycosylation is a highly prevalent posttranslational modification (PTM), whose role has been linked to a wide variety of biological activities [1,2], ranging from protein folding [3] to immune system response [4]. Unlike most biomolecules, oligosaccharides often exist as several isomeric forms with diverse linkages, and may form linear or branched structures.…”

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confidence: 99%

Electron detachment dissociation of neutral and sialylated oligosaccharides

Adamson

Håkansson

2007

J. Am. Soc. Mass Spectrom.

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Electron detachment dissociation (EDD) has recently been shown by Amster and coworkers to constitute a valuable analytical approach for structural characterization of glycosaminoglycans. Here, we extend the application of EDD to neutral and sialylated oligosaccharides. Both branched and linear structures are examined, to determine whether branching has an effect on EDD fragmentation behavior. EDD spectra are compared to collisional activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD) spectra of the doubly and singly deprotonated species. Our results demonstrate that EDD of both neutral and sialylated oligosaccharides provides structural information that is complementary to that obtained from both CAD and IRMPD. In all cases, EDD resulted in additional cross-ring cleavages. In most cases, cross-ring fragmentation obtained by EDD is more extensive than that obtained from IRMPD or CAD. Our results also indicate that branching does not affect EDD fragmentation, contrary to what has been observed for electron capture dissociation (ECD). . Unlike most biomolecules, oligosaccharides often exist as several isomeric forms with diverse linkages, and may form linear or branched structures. Complete structural characterization of oligosaccharides requires the determination of constituent monosaccharides, their linkage, sequence, and branching patterns. Given their diversity and structural complexity, structural elucidation of oligosaccharides often relies upon a wide range of analytical methodologies, of which nuclear magnetic resonance spectroscopy and mass spectrometry are two vital techniques. Tandem mass spectrometry (MS/MS) is widely used for glycan structural characterization [5][6][7], due to the advent of instruments that provide high-quality spectra from even low-abundance molecular species.Tandem mass spectra of oligosaccharides consist mainly of glycosidic and cross-ring product ions. Glycosidic cleavage occurs between monosaccharide units and provides information regarding saccharide sequence and branching. Cross-ring cleavages can provide valuable information regarding saccharide linkage, particularly when occurring at branching residues. Several factors are known to affect oligosaccharide fragmentation and the degree of cross-ring fragmentation, such as the ionizing cation, the lifetime of the ion before detection, and the energy deposited into the ion.Typically, neutral oligosaccharides are analyzed in positive-ion mode, by their protonated forms or through metal ion adduction. In addition, chemical derivatization such as permethylation is widely used to increase sensitivity, reduce molecular ion lability, and produce structurally diagnostic product ions [8 -10]. Low-energy activation methods, such as collisional activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD), applied to protonated oligosaccharides results in predominantly glycosidic cleavages. However, oligosaccharides ionized with alkali, alkaline earth, and transition metals often fragment to yield more cro...

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Glycobiology: Toward Understanding the Function of Sugars

Cited by 2,860 publications

References 173 publications

Functional roles of glycogene and N‐glycan in multidrug resistance of human breast cancer cells

Functional roles of glycogene and N‐glycan in multidrug resistance of human breast cancer cells

Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment

Electron detachment dissociation of neutral and sialylated oligosaccharides

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