A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates

Grayson, Elizabeth J.; Bernardes, Gonçalo J. L.; Chalker, Justin M.; Boutureira, Omar; Koeppe, Julia R.; Davis, Benjamin G.

doi:10.1002/anie.201006327

Cited by 74 publications

(63 citation statements)

References 46 publications

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“…9 A different strategy, known as indiscriminate glycosylation, relies on the use of 2-iminomethoxyethyl thioglycosides (IME) and takes advantage from the high abundance of lysine residues on the protein surface, allowing the introduction of various saccharide units for each molecule of protein. 8 For example, Pearce and coworkers employed this methodology to incorporate up to 20 000 glycan moieties onto the surface of adenovirus.…”

Section: 78mentioning

confidence: 99%

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

et al. 2014

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In this paper a series of 2-iminomethoxyethyl mannose-based mono-and disaccharides have been synthesized by a chemoenzymatic approach and used in coupling reactions with 3-amino groups of lysine residues in a model protein (ribonuclease A, RNase A) to give semisynthetic neoglycoconjugates. In order to study the influence of structure of the glycans on the conjugation outcomes, an accurate characterization of the prepared neoglycoproteins was performed by a combination of ESI-MS and LC-MS analytical methods. The analyses of the chymotryptic digests of the all neoglycoconjugates revealed six Lys-glycosylation sites with a the following order of lysine reactivity: Lys 1 [ Lys 91 y Lys 31 > Lys 61 y Lys 66. A computational analysis of the reactivity of each lysine residue has been also carried out considering several parameters (amino acids surface exposure and pK a , protein flexibility). The in silico evaluation seems to confirm the order in lysine reactivity resulting from proteomic analysis.

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Section: 78mentioning

confidence: 99%

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

et al. 2014

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“…Herein, we will focus on recent developments in using synthetic glycoengineered vaccines to create more defined therapeutics. Advances in the fields of protein conjugation have also expanded the techniques available to generate carbohydrate vaccines selectively attached to protein carriers (Gamblin et al, 2009; Grayson et al, 2011). For those interested, several reviews are available that cover more in-depth progress of carbohydrate-based vaccines against bacteria (Pozsgay, 2008), HIV (Wang, 2006), and cancer (Cipolla et al, 2008; Ouerfelli et al, 2005).…”

Section: Engineered Glycans and Glycan Mimics As Therapeutic Agentsmentioning

confidence: 99%

Glycotherapy: New Advances Inspire a Reemergence of Glycans in Medicine

Hudak

Bertozzi

2014

Chemistry & Biology

203

176

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The beginning of the 20th century marked the dawn of modern medicine with glycan-based therapies at the forefront. However, glycans quickly became overshadowed as DNA- and protein-focused treatments became readily accessible. The recent development of new tools and techniques to study and produce structurally defined carbohydrates has spurred renewed interest in the therapeutic applications of glycans. This review focuses on advances within the past decade that are bringing glycan-based treatments back to the forefront of medicine and the technologies that are driving these efforts. These include the use of glycans themselves as therapeutic molecules as well as engineering protein and cell surface glycans to suit clinical applications. Glycan therapeutics offer a rich and promising frontier for developments in the academic, biopharmaceutical, and medical fields.

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“…Advances in the field of protein conjugation have also expanded the techniques available to generate carbohydrate vaccines, selectively attached to protein carriers. [36,37] The most successful case to utilize synthetically derived vaccine has been the production of the Cuban Hib vaccine; the first clinically approved, fully synthetic carbohydrate vaccine based on the structure of the capsular polysaccharide antigen from Hib (32). The pentasaccharide conjugated to tetanus toxin (TT) is produced under GMP conditions in scales large enough to be incorporated in the Cuba's current system planned vaccination.…”

Section: Vaccines Based On Carbohydratesmentioning

confidence: 99%

Glycodendrimers and Their Derivatives as Potential Therapeutic Agents

Shchelik¹,

Magasumova²,

Yu³

2015

MHC

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A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates

Abstract: A sweet solution: A strategy for the synthesis of well‐defined carbohydrate‐based vaccines is presented. The approach couples complex oligosaccharide synthesis to site‐specific conjugation methodology to provide pure glycoprotein vaccine candidates (see scheme).

Cited by 74 publications

References 46 publications

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

Glycotherapy: New Advances Inspire a Reemergence of Glycans in Medicine

Glycodendrimers and Their Derivatives as Potential Therapeutic Agents

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