Glycoprotein Synthesis: An Update

Gamblin, David P.; Scanlan, Eoin M.; Davis, Benjamin G.

doi:10.1021/cr078291i

Cited by 564 publications

(426 citation statements)

References 383 publications

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“…The fourth fragment, peptide 11 (shown in Scheme 5), was prepared by treatment of the resinbound protected peptide with Cocktail B. The four fragments (8)(9)(10)(11) were sequentially merged through a series of iterative NCL/thiazolidine removal sequences (Scheme 5). Thus, peptide 11, possessing an N-terminal cysteine residue, and peptide 10, bearing a latent C-terminal thioester, were combined in phosphate buffer solution containing guanidine•HCl, TCEP•HCl, and MPAA at pH 7.2-7.4.…”

Section: Resultsmentioning

confidence: 99%

Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations

Brailsford

Danishefsky

2012

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

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Section: Resultsmentioning

confidence: 99%

Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations

Brailsford

Danishefsky

2012

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

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“…In contrast, monosaccharide building blocks can differ in arrangement of atoms in three-dimensional space and they possess the ability to form highly branched molecules. Glycosylation machinery and functions of many glycoconjugates have been described in detail in recent years and specific glycan-lectin pairs were defined as crucial for the interaction of biomolecules during immune recognition, inflammation, and infection of pathogenic organisms [10,11].…”

Section: 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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“…As a result, synthetic homogeneous glycopeptides and glycoproteins emerge as indispensable tools for functional studies and for drug/vaccine discoveries. Many elegant chemical and biochemical strategies have been explored for making homogeneous glycoproteins and mimics, including total chemical synthesis with native chemical ligation (13)(14)(15)(16)(17), chemoselective ligation (18,19), chemoenzymatic synthesis (20 -24), and glycosylation pathway engineering in host expression systems (25)(26)(27)(28). As part of these efforts, we have attempted to develop a chemoenzymatic method for construction of complex N-glycopeptides and glycoproteins that is based on the transglycosylation activity of a class of endo-␤-N-acetylglucosaminidases (the endoglycosidases that hydrolyze N-glycans of glycoproteins) for convergent native ligation of preassembled glycans and GlcNAc-peptide/ protein (20,23,24).…”

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confidence: 99%

Endo-F3 Glycosynthase Mutants Enable Chemoenzymatic Synthesis of Core-fucosylated Triantennary Complex Type Glycopeptides and Glycoproteins

Giddens

Lomino

Amin

et al. 2016

Journal of Biological Chemistry

115

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Chemoenzymatic synthesis is emerging as a promising approach to the synthesis of homogeneous glycopeptides and glycoproteins highly demanded for functional glycomics studies, but its generality relies on the availability of a range of enzymes with high catalytic efficiency and well defined substrate specificity. We describe in this paper the discovery of glycosynthase mutants derived from Elizabethkingia meningoseptica endoglycosidase F3 (Endo-F3) of the GH18 family, which are devoid of the inherent hydrolytic activity but are able to take glycan oxazolines for transglycosylation. Notably, the Endo-F3 D165A and D165Q mutants demonstrated high acceptor substrate specificity toward ␣1,6-fucosyl-GlcNAc-Asn or ␣1, 6-fucosyl-GlcNAc-polypeptide in transglycosylation, enabling a highly convergent synthesis of core-fucosylated, complex CD52 glycopeptide antigen. The Endo-F3 mutants were able to use both bi-and triantennary glycan oxazolines as substrates for transglycosylation, in contrast to previously reported endoglycosidases derived from Endo-S, Endo-M, Endo-D, and Endo-A mutants that could not recognize triantennary N-glycans. Using rituximab as a model system, we have further demonstrated that the Endo-F3 mutants are highly efficient for glycosylation remodeling of monoclonal antibodies to produce homogeneous intact antibody glycoforms. Interestingly, the new triantennary glycan glycoform of antibody showed much higher affinity for galectin-3 than that of the commercial antibody. The Endo-F3 mutants represent the first endoglycosidase-based glycosynthases capable of transferring triantennary complex N-glycans, which would be very useful for glycoprotein synthesis and glycosylation remodeling of antibodies.Protein glycosylation is one of the most prevalent posttranslational modifications, found in almost all living organisms ranging from bacteria to eukaryotes (1). Glycosylation can profoundly affect a protein's intrinsic properties, such as folding, stability, intracellular trafficking, and immunogenicity. In addition, the oligosaccharide components of glycoproteins can participate directly in a number of important biological recognition processes, including cell adhesion, signaling, hostpathogen interactions, and immune responses (2-8). It is well documented that subtle changes in glycosylation can lead to a significant impact on the biological functions and, in the case of therapeutic glycoproteins, such as monoclonal antibodies, the in vivo stability and therapeutic efficacy (7, 9 -12). Natural and recombinant glycoproteins are usually produced as mixtures of glycoforms that differ only in the structures of pendant glycans, from which pure glycoforms are extremely difficult to isolate by current chromatographic techniques. As a result, synthetic homogeneous glycopeptides and glycoproteins emerge as indispensable tools for functional studies and for drug/vaccine discoveries. Many elegant chemical and biochemical strategies have been explored for making homogeneous glycoproteins and mimics, including total chemic...

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Glycoprotein Synthesis: An Update

Abstract: Scheme 2. Methods for Preparation of N-Linked Glycopeptides Scheme 3. Methods for Preparation of O-Linked Glycopeptides

Cited by 564 publications

References 383 publications

Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations

Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Endo-F3 Glycosynthase Mutants Enable Chemoenzymatic Synthesis of Core-fucosylated Triantennary Complex Type Glycopeptides and Glycoproteins

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