Imperial College London

DrWengangChai

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2596w.chai

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

146 results found

Huang C, Sun S, Yan J, Wang H, Zhou J, Gao H, Xie W, Li Y, Chai Wet al., 2020, Identification of carbohydrate peripheral epitopes important for recognition by positive-ion MALDI multistage mass spectrometry, CARBOHYDRATE POLYMERS, Vol: 229, ISSN: 0144-8617

Journal article

Wu N, Silva LM, Liu Y, Zhang Y, Gao C, Zhang F, Fu L, Peng Y, Linhardt R, Kawasaki T, Mulloy B, Chai W, Feizi Tet al., 2019, Glycan markers of human stem cells assigned with beam search arrays, Molecular and Cellular Proteomics, Vol: 18, Pages: 1981-2002, ISSN: 1535-9476

Glycan antigens recognized by monoclonal antibodies have served as stem cell markers. To understand regulation of their biosynthesis and their roles in stem cell behavior precise assignments are required. We have applied state-of-the-art glycan array technologies to compare the glycans bound by five antibodies that recognize carbohydrates on human stem cells. These are: FC10.2, TRA-1-60, TRA-1-81, anti-i and R-10G. Microarray analyses with a panel of sequence-defined glycans corroborate that FC10.2, TRA-1-60, TRA-1-81 recognize the type 1-(Galβ-3GlcNAc)-terminating backbone sequence, Galβ-3GlcNAcβ-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc, and anti-i, the type 2-(Galβ-4GlcNAc) analog, Galβ-4GlcNAcβ-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc, and we determine substituents they can accommodate. They differ from R-10G, which requires sulfate. By Beam Search approach, starting with an antigen-positive keratan sulfate polysaccharide, followed by targeted iterative microarray analyses of glycan populations released with keratanases and mass spectrometric monitoring, R-10G is assigned as a mono-sulfated type 2 chain with 6-sulfation at the penultimate N-acetylglucosamine, Galβ-4GlcNAc(6S)β-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc. Microarray analyses using newly synthesized glycans corroborate the assignment of this unique determinant raising questions regarding involvement as a ligand in the stem cell niche.

Journal article

Huang C, Yan J, Zhan L, Zhao M, Zhou J, Gao H, Xie W, Li Y, Chai Wet al., 2019, Linkage and sequence analysis of neutral oligosaccharides by negative-ion MALDI tandem mass spectrometry with laser-induced dissociation, ANALYTICA CHIMICA ACTA, Vol: 1071, Pages: 25-35, ISSN: 0003-2670

Journal article

Cong X, Sun X-M, Qi J-X, Li H-B, Chai W-G, Zhang Q, Wang H, Kong X-Y, Song J, Pang L-L, Jin M, Li D-D, Tan M, Duan Z-Jet al., 2019, GII.13/21 Noroviruses Recognize Glycans with a Terminal beta-Galactose via an Unconventional Glycan Binding Site, JOURNAL OF VIROLOGY, Vol: 93, ISSN: 0022-538X

Journal article

Yan J, Ding J, Jin G, Duan Z, Yang F, Li D, Zhou H, Li M, Guo Z, Chai W, Liang Xet al., 2019, Profiling of Human Milk Oligosaccharides for Lewis Epitopes and Secretor Status by Electrostatic Repulsion Hydrophilic Interaction Chromatography Coupled with Negative-Ion Electrospray Tandem Mass Spectrometry, ANALYTICAL CHEMISTRY, Vol: 91, Pages: 8199-8206, ISSN: 0003-2700

Journal article

Li Z, Chai W, 2019, Mucin O-glycan microarrays, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 56, Pages: 187-197, ISSN: 0959-440X

Journal article

Chandra N, Liu Y, Liu J-X, Fraengsmyr L, Wu N, Silva LM, Lindstrom M, Chai W, Domellof FP, Feizi T, Arnberg Net al., 2019, Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37, Viruses, Vol: 11, ISSN: 1999-4915

Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.

Journal article

Li S, Li J, Mao G, Wu T, Lin D, Hu Y, Ye X, Tian D, Chai W, Linhardt RJ, Chen Set al., 2019, Fucosylated chondroitin sulfate from Isostichopus badionotus alleviates metabolic syndromes and gut microbiota dysbiosis induced by high-fat and high-fructose diet, INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Vol: 124, Pages: 377-388, ISSN: 0141-8130

Journal article

Sun S, Huang C, Wang Y, Liu Y, Zhang J, Zhou J, Gao F, Yang F, Chen R, Mulloy B, Chai W, Li Y, Bu Det al., 2018, Toward Automated Identification of Glycan Branching Patterns Using Multistage Mass Spectrometry with Intelligent Precursor Selection, ANALYTICAL CHEMISTRY, Vol: 90, Pages: 14412-14422, ISSN: 0003-2700

Journal article

Loureiro LR, Sousa DP, Ferreira D, Chai W, Lima L, Pereira C, Lopes CB, Correia VG, Silva LM, Li C, Santos LL, Ferreira JA, Barbas A, Palma AS, Novo C, Videira PAet al., 2018, Novel monoclonal antibody L2A5 specifically targeting sialyl-Tn and short glycans terminated by alpha-2–6 sialic acids, Scientific Reports, Vol: 8, ISSN: 2045-2322

Incomplete O-glycosylation is a feature associated with malignancy resulting in the expression of truncated glycans such as the sialyl-Tn (STn) antigen. Despite all the progress in the development of potential anti-cancer antibodies, their application is frequently hindered by low specificities and cross-reactivity. In this study, a novel anti-STn monoclonal antibody named L2A5 was developed by hybridoma technology. Flow cytometry analysis showed that L2A5 specifically binds to sialylated structures on the cell surface of STn-expressing breast and bladder cancer cell lines. Moreover, immunoblotting assays demonstrated reactivity to tumour-associated O-glycosylated proteins, such as MUC1. Tumour recognition was further observed using immunohistochemistry assays, which demonstrated a high sensitivity and specificity of L2A5 mAb towards cancer tissue, using bladder and colorectal cancer tissues. L2A5 staining was exclusively tumoural, with a remarkable reactivity in invasive and metastasis sites, not detectable by other anti-STn mAbs. Additionally, it stained 20% of cases of triple-negative breast cancers, suggesting application in diseases with unmet clinical needs. Finally, the fine specificity was assessed using glycan microarrays, demonstrating a highly specific binding of L2A5 to core STn antigens and additional ability to bind 2–6-linked sialyl core-1 probes. In conclusion, this study describes a novel anti-STn antibody with a unique binding specificity that can be applied for cancer diagnostic and future development of new antibody-based therapeutic applications.

Journal article

Sun X, Li D, Qi J, Chai W, Wang L, Wang L, Peng R, Wang H, Zhang Q, Pang L, Kong X, Wang H, Jin M, Gao GF, Duan Zet al., 2018, Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

Journal article

Sun X, Wang L, Qi J, Li D, Wang M, Cong X, Peng R, Chai W, Zhang Q, Wang H, Wen H, Gao GF, Tan M, Duan Zet al., 2018, Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

Journal article

Chai W, Zhang Y, Mauri L, Ciampa MG, Mulloy B, Sonnino S, Feizi Tet al., 2018, Assignment by Negative-Ion Electrospray Tandem Mass Spectrometry of the Tetrasaccharide Backbones of Monosialylated Glycans Released from Bovine Brain Gangliosides, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 29, Pages: 1308-1318, ISSN: 1044-0305

Gangliosides, as plasma membrane-associated sialylated glycolipids, are antigenic structures and they serve as ligands for adhesion proteins of pathogens, for toxins of bacteria, and for endogenous proteins of the host. The detectability by carbohydrate-binding proteins of glycan antigens and ligands on glycolipids can be influenced by the differing lipid moieties. To investigate glycan sequences of gangliosides as recognition structures, we have underway a program of work to develop a “gangliome” microarray consisting of isolated natural gangliosides and neoglycolipids (NGLs) derived from glycans released from them, and each linked to the same lipid molecule for arraying and comparative microarray binding analyses. Here, in the first phase of our studies, we describe a strategy for high-sensitivity assignment of the tetrasaccharide backbones and application to identification of eight of monosialylated glycans released from bovine brain gangliosides. This approach is based on negative-ion electrospray mass spectrometry with collision-induced dissociation (ESI-CID-MS/MS) of the desialylated glycans. Using this strategy, we have the data on backbone regions of four minor components among the monosialo-ganglioside-derived glycans; these are of the ganglio-, lacto-, and neolacto-series.

Journal article

Lenman A, Liaci AM, Liu Y, Frangsmyr L, Frank M, Blaum BS, Chai W, Podgorski II, Harrach B, Benko M, Feizi T, Stehle T, Arnberg Net al., 2018, Polysialic acid is a cellular receptor for human adenovirus 52, Proceedings of the National Academy of Sciences of the United States of America, Vol: 115, Pages: E4264-E4273, ISSN: 0027-8424

Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.

Journal article

Yan J, Ding J, Jin G, Yu D, Yu L, Guo Z, Chai W, Liang Xet al., 2018, Profiling of sialylated oligosaccharides in mammalian milk using online solid phase extraction-hydrophilic interaction chromatography coupled with negative-ion electrospray mass spectrometry, Analytical Chemistry, Vol: 90, Pages: 3174-3182, ISSN: 0003-2700

Sialylated oligosaccharides are important components in mammalian milk. They play a key role in the health and growth of infants by helping to shape up infant’s gastrointestinal microbiota and defense against infection by various pathogenic agents. A detailed knowledge of the structures, compositions, and quantities of the sialylated milk oligosaccharides (SMOs) is a prerequisite for understanding their biological roles. However, because of the presence of very large amounts of lactose and neutral oligosaccharides, accurate analysis of SMOs is difficult. A pretreatment step is required to remove lactose and neutral oligosaccharides but conventional off-line pretreatment methods are time-consuming and of poor reproducibility. In this presentation, we linked solid-phase extraction (SPE) with hydrophilic interaction chromatography (HILIC) followed by mass spectrometry (MS) identification for the analysis of SMOs. A SPE column with electrostatic repulsion function was used for removal of lactose and neutral oligosaccharides, a HILIC analytical column for separation of the SMOs, and negative-ion electrospray ionization tandem MS was used for their identification and sequencing. The success of the established online SPE-HILIC-MS method was demonstrated by profiling of SMOs in human to investigate detailed SMO changes during lactation period and in animals to compare the difference in SMO contents among the different species.

Journal article

Liu Y, Palma AS, Ten F, Chai Wet al., 2018, Insights Into Glucan Polysaccharide Recognition Using Glucooligosaccharide Microarrays With Oxime-Linked Neoglycolipid Probes, CHEMICAL GLYCOBIOLOGY, PT B: MONITORING GLYCANS AND THEIR INTERACTIONS, Editors: Imperiali, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 139-167

Book chapter

Li Z, Gao C, Zhang Y, Palma A, Childs R, Silva L, Liu Y, Jiang X, Liu Y, Chai W, Feizi Tet al., 2017, O-Glycome beam search arrays for carbohydrate ligand discovery, Molecular and Cellular Proteomics, Vol: 17, Pages: 121-133, ISSN: 1535-9476

O-glycosylation is a post-translational modification of proteins crucial to molecular mechanisms in health and disease. O-glycans are typically highly heterogeneous. The involvement of specific O-glycan sequences in many bio-recognition systems is yet to be determined due to a lack of efficient methodologies. We describe here a targeted microarray approach: O-glycome beam search that is both robust and efficient for O-glycan ligand-discovery. Substantial simplification of the complex O-glycome profile and facile chromatographic resolution is achieved by arraying O-glycans as branches, monitoring by mass spectrometry, focusing on promising fractions, and on-array immuno-sequencing. This is orders of magnitude more sensitive than traditional methods. We have applied beam search approach to porcine stomach mucin and identified extremely minor components previously undetected within the O-glycome of this mucin that are ligands for the adhesive proteins of two rotaviruses. The approach is applicable to O-glycome recognition studies in a wide range of biological settings to give insights into glycan recognition structures in natural microenvironments.

Journal article

Boyle MJ, Skidmore M, Dickerman B, Cooper L, Devlin A, Yates E, Horrocks P, Freeman C, Chai W, Beeson JGet al., 2017, Identification of Heparin Modifications and Polysaccharide Inhibitors of Plasmodium falciparum Merozoite Invasion That Have Potential for Novel Drug Development, Antimicrobial Agents and Chemotherapy, Vol: 61, Pages: e00709-17-e00709-17, ISSN: 0066-4804

Journal article

Zhang H, Palma AS, Zhang Y, Childs RA, Liu Y, Mitchell DA, Guidolin LS, Weigel W, Mulloy B, Ciocchini AE, Feizi T, Chai Wet al., 2016, Generation and characterization of β1,2-gluco-oligosaccharide probes from Brucella abortus cyclic β-glucan and their recognition by C-type lectins of the immune system, Glycobiology, Vol: 26, Pages: 1086-1096, ISSN: 1460-2423

The β1,2-glucans produced by bacteria are important in invasion, survival andimmunomodulation in infected hosts be they mammals or plants. However, there has been alack of information on proteins which recognize these molecules. This is partly due to theextremely limited availability of the sequence-defined oligosaccharides and derived probesfor use in the study of their interactions. Here we have used the cyclic β1,2-glucan (CβG) ofthe bacterial pathogen Brucella abortus, after removal of succinyl side chains, to preparelinearized oligosaccharides which were used to generate microarrays. We describe optimizedconditions for partial depolymerization of the cyclic glucan by acid hydrolysis and conversionof the β1,2-gluco-oligosaccharides, with degrees of polymerization 2-13, to neoglycolipids forthe purpose of generating microarrays. By microarray analyses we show that the C-type lectinreceptor DC-SIGNR, like the closely related DC-SIGN we investigated earlier, binds to theβ1,2-gluco-oligosaccharides, as does the soluble immune effector serum mannose-bindingprotein. Exploratory studies with DC-SIGN are suggestive of the recognition also of the intactCβG by this receptor. These findings open the way to unravelling mechanisms ofimmunomodulation mediated by β1,2-glucans in mammalian systems.

Journal article

Mulloy B, Wu N, Gyapon-Quast F, Lin L, Zhang F, Pickering MC, Linhardt RJ, Feizi T, Chai Wet al., 2016, Abnormally high content of free glucosamine residues identified in a preparation of commercially available porcine intestinal heparan sulfate, Analytical Chemistry, Vol: 88, Pages: 6648-6652, ISSN: 1520-6882

Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. 1H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies.

Journal article

Gao C, Zhang Y, Liu Y, Ten F, Chai Wet al., 2015, Negative-Jon Electrospray Tandem Mass Spectrometry and Microarray Analyses of Developmentally Regulated Antigens Based on Type 1 and Type 2 Backbone Sequences, Analytical Chemistry, Vol: 87, Pages: 11871-11878, ISSN: 1520-6882

Type 1 (Galβ1-3GlcNAc) and type 2 (Galβ1-4GlcNAc) sequences are constituents of the backbones of alarge family of glycans of glycoproteins and glycolipids whosebranching and peripheral substitutions are developmentallyregulated. It is highly desirable to have microsequencingmethods that can be used to precisely identify and monitorthese oligosaccharide sequences with high sensitivity. Negative-ionelectrospray tandem mass spectrometry withcollision-induced dissociation has been used for characterizationof branching points, peripheral substitutions, andpartial assignment of linkages in reducing oligosaccharides. Wenow extend this method to characterizing entire sequences oflinear type 1 and type 2 chain-based glycans, focusing on thetype 1 and type 2 units in the internal regions including the linkages connecting type 1 and type 2 disaccharide units. We applythe principles to sequence analysis of closely related isomeric oligosaccharides and demonstrate by microarray analyses distinctbinding activities of antibodies and a lectin toward various combinations of type 1 and 2 units joined by 1,3- and 1,6-linkages.These sequence-specific carbohydrate-binding proteins are in turn valuable tools for detecting and distinguishing the type 1 andtype 2-based developmentally regulated glycan sequences.

Journal article

Palma AS, Liu Y, Zhang H, Zhang Y, McCleary BV, Yu G, Huang Q, Guidolin LS, Ciocchini AE, Torosantucci A, Wang D, Carvalho AL, Fontes CMGA, Mulloy B, Childs RA, Feizi T, Chai Wet al., 2015, Unravelling Glucan Recognition Systems by Glycome Microarrays Using the Designer Approach and Mass Spectrometry, Molecular & Cellular Proteomics, Vol: 14, Pages: 974-988, ISSN: 1535-9484

Glucans are polymers of D-glucose with differing linkages in linear or branched sequences. They are constituents of microbial and plant cell-walls and involved in important bio-recognition processes, including immunomodulation, anticancer activities, pathogen virulence, and plant cell-wall biodegradation. Translational possibilities for these activities in medicine and biotechnology are considerable. High-throughput micro-methods are needed to screen proteins for recognition of specific glucan sequences as a lead to structure–function studies and their exploitation. We describe construction of a “glucome” microarray, the first sequence-defined glycome-scale microarray, using a “designer” approach from targeted ligand-bearing glucans in conjunction with a novel high-sensitivity mass spectrometric sequencing method, as a screening tool to assign glucan recognition motifs. The glucome microarray comprises 153 oligosaccharide probes with high purity, representing major sequences in glucans. Negative-ion electrospray tandem mass spectrometry with collision-induced dissociation was used for complete linkage analysis of gluco-oligosaccharides in linear “homo” and “hetero” and branched sequences. The system is validated using antibodies and carbohydrate-binding modules known to target α- or β-glucans in different biological contexts, extending knowledge on their specificities, and applied to reveal new information on glucan recognition by two signaling molecules of the immune system against pathogens: Dectin-1 and DC-SIGN. The sequencing of the glucan oligosaccharides by the MS method and their interrogation on the microarrays provides detailed information on linkage, sequence and chain length requirements of glucan-recognizing proteins, and are a sensitive means of revealing unsuspected sequences in the polysaccharides.

Journal article

Panagos CG, Thomson DS, Moss C, Hughes AD, Kelly MS, Liu Y, Chai W, Venkatasamy R, Spina D, Page CP, Hogwood J, Woods RJ, Mulloy B, Bavington CD, Uhrin Det al., 2014, Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY, Journal of Biological Chemistry, Vol: 289, Pages: 28284-28298, ISSN: 0021-9258

Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and photochemical depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention.

Journal article

Suits MDL, Pluvinage B, Law A, Liu Y, Palma AS, Chai W, Feizi T, Boraston ABet al., 2014, Conformational analysis of the Streptococcus pneumoniae hyaluronate lyase and characterization of Its hyaluronan-specific carbohydrate-binding module, Journal of Biological Chemistry, Vol: 289, Pages: 27264-27277, ISSN: 0021-9258

For a subset of pathogenic microorganisms, including Streptococcus pneumoniae, the recognition and degradation of host hyaluronan contributes to bacterial spreading through the extracellular matrix and enhancing access to host cell surfaces. The hyaluronate lyase (Hyl) presented on the surface of S. pneumoniae performs this role. Using glycan microarray screening, affinity electrophoresis, and isothermal titration calorimetry we show that the N-terminal module of Hyl is a hyaluronan-specific carbohydrate-binding module (CBM) and the founding member of CBM family 70. The 1.2 Å resolution x-ray crystal structure of CBM70 revealed it to have a β-sandwich fold, similar to other CBMs. The electrostatic properties of the binding site, which was identified by site-directed mutagenesis, are distinct from other CBMs and complementary to its acidic ligand, hyaluronan. Dynamic light scattering and solution small angle x-ray scattering revealed the full-length Hyl protein to exist as a monomer/dimer mixture in solution. Through a detailed analysis of the small angle x-ray scattering data, we report the pseudoatomic solution structures of the monomer and dimer forms of the full-length multimodular Hyl.

Journal article

Palma AS, Feizi T, Childs RA, Chai W, Liu Yet al., 2014, The neoglycolipid (NGL)-based oligosaccharide microarray system poised to decipher the meta-glycome (vol 21, pg 170, 2014), CURRENT OPINION IN CHEMICAL BIOLOGY, Vol: 21, Pages: 170-170, ISSN: 1367-5931

Journal article

Kanagawa M, Liu Y, Hanashima S, Ikeda A, Chai W, Nakano Y, Kojima-Aikawa K, Feizi T, Yamaguchi Yet al., 2014, Structural Basis for Multiple Sugar Recognition of Jacalin-related Human ZG16p Lectin, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 16954-16965

Journal article

Gao C, Liu Y, Zhang H, Zhang Y, Fukuda MN, Palma AS, Kozak RP, Childs RA, Nonaka M, Li Z, Siegel DL, Hanfland P, Peehl DM, Chai W, Greene MI, Ten Fet al., 2014, Carbohydrate Sequence of the Prostate Cancer-associated Antigen F77 Assigned by a Mucin O-Glycome Designer Array, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 16462-16477

Journal article

Palma AS, Feizi T, Childs RA, Chai W, Liu Yet al., 2014, The neoglycolipid (NGL)-based oligosaccharide microarray system poised to decipher the meta-glycome, CURRENT OPINION IN CHEMICAL BIOLOGY, Vol: 18, Pages: 87-94, ISSN: 1367-5931

Journal article

Crusat M, Liu J, Palma AS, Childs RA, Liu Y, Wharton SA, Lin YP, Coombs PJ, Martin SR, Matrosovich M, Chen Z, Stevens DJ, Vo MH, Tran TT, Le NTN, Lam AN, Do QH, van Doorn HR, Tran TH, Conradt HS, Kiso M, Gamblin SJ, Chai W, Skehel JJ, Hay AJ, Farrar J, de Jong MD, Feizi Tet al., 2013, Changes in the hemagglutinin of H5N1 viruses during human infection - Influence on receptor binding, VIROLOGY, Vol: 447, Pages: 326-337, ISSN: 0042-6822

Journal article

Cerqueira C, Liu Y, Kuehling L, Chai W, Hafezi W, van Kuppevelt TH, Kuehn JE, Feizi T, Schelhaas Met al., 2013, Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure, CELLULAR MICROBIOLOGY, Vol: 15, Pages: 1818-1836, ISSN: 1462-5814

Journal article

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