Glycan Microarrays for Decoding the Glycome

Rillahan, Cory D.; Paulson, James C.

doi:10.1146/annurev-biochem-061809-152236

Cited by 401 publications

(355 citation statements)

References 159 publications

(262 reference statements)

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“…Microarray-Glycan microarrays are a unique tool for rapidly identifying possible receptors for pathogen attachment (58,59). A variety of viral proteins or whole viruses, including several RV VP8*s, have been analyzed on glycan arrays, which provided important information to direct biological and structural studies.…”

Section: Binding Of Rv Cell Attachment Proteins To the Cfg Defined Glmentioning

confidence: 99%

Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses

Lasanajak

Song

et al. 2014

Molecular & Cellular Proteomics

114

126

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Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155 (G10P[11]) and RV3(G3P[6]) and a bovine strain, B223 (G10P[11]). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadataassisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo-and endo-glycosidase digestion of the SGM, coupled with independent MS n analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MS n are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. Molecular & Cellular Proteomics 13:

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Section: Binding Of Rv Cell Attachment Proteins To the Cfg Defined Glmentioning

confidence: 99%

Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses

Lasanajak

Song

et al. 2014

Molecular & Cellular Proteomics

114

126

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“…Glycan microarrays (20,21), which contain hundreds of carbohydrates immobilized on microscope slides, provide a multiplex assay for analyzing serum antiglycan antibodies that uses only minute amounts of valuable glycans and clinical samples (e.g., only 2-4 μL of serum). This approach, referred to as "glycoimmunomics," generates a comprehensive profile of antiglycan immune responses.…”

Section: Significancementioning

confidence: 99%

Humoral response to a viral glycan correlates with survival on PROSTVAC-VF

Campbell

Gulley

Oyelaran

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Because individual cancer patients differ considerably in their clinical benefits from immunotherapies, early indicators of response could help physicians personalize treatments. Unfortunately, conventional clinical response criteria can be misleading for cancer vaccines. Herein, we show that early humoral responses to xenogenic Forssman disaccharide displayed on PROSTVAC-VF’s viral vectors correlate with long-term survival of vaccinated prostate cancer patients. The survival correlation for anti-Forssman responses was observed consistently when PROSTVAC-VF was used either as monotherapy or combined with the radiopharmaceutical Quadramet. Monitoring postvaccination anti-Forssman humoral responses could offer a simple indicator of response many months before conventional clinical response criteria become reliable. Finally, this study suggests that modifying glycans may improve poxvirus-based vaccines even when not specifically designed to target glycans.

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“…Arrays differ in the range of glycans/lectins and the manner in which they are displayed on the chip surfaces as this can be an influencing factor in the recognition of the glycan [21]. In many cases, specific thermodynamically stable conformation is needed for receptor recognition and high binding affinities are only achieved in the presence of specific neighbouring residues.…”

Section: Characterization Of Carbohydrate-lectin Interactionsmentioning

confidence: 99%

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Utratna¹,

Deegan²,

Joshi³

2016

J Bioterror Biodef

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Pathogen adherence to a host cell is one of the first essential steps for establishing invasion, colonization and release of virulence factors such as toxins. Understanding the mechanisms used by pathogens and toxins to adhere and invade human cells could lead to the development of new strategies for preventing and controlling the spread of infectious diseases. This review focuses on carbohydrate-lectin interactions utilized by selected biothreat agents to bind and invade host cells. The principle of using anti-adhesion molecules, based on glycobiology research, has already been shown to be effective in the treatment of influenza. Therefore, translating the same principle to other biothreat agents that mediate invasion of a host cell through carbohydrate-lectin mechanisms is a very promising strategy. We investigate recent literature to highlight the latest developments in the field of glycobiology focused on inhibiting the initial steps of pathogen invasion, with examples for bacteria, toxin and virus interactions. The successful glycomimetics and glycoconjugates represent strategies for interruption of adhesion by single molecules and in multivalent systems against uropathogenic E. coli, several toxins (Shiga-like, cholera, botulinum) and wellknown or emerging viruses (influenza, HIV, Ebola, and Zika). This review provides promising directions and prophylactic as well as therapeutic potential of anti-adhesive strategies against selected biothreat targets.

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Glycan Microarrays for Decoding the Glycome

Cited by 401 publications

References 159 publications

Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses

Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses

Humoral response to a viral glycan correlates with survival on PROSTVAC-VF

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

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