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/ange.201006327

Cited by 16 publications

(4 citation statements)

References 48 publications

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“… 5 , 6 In a typical workflow, the protein is first engineered to display a uniquely reactive functional group that serves as a point of attachment for glycans armed with complementary functionality. Popular chemistries include disulfide conjugation, 7 , 8 elimination/addition reactions, 9 , 10 azide/alkyne-based click chemistries, 11 − 13 and oxime formation. 14 − 17 …”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags

Smith

Giddens

Iavarone³

et al. 2014

Bioconjugate Chem.

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Glycoproteins with chemically defined glycosylation sites and structures are important biopharmaceutical targets and critical tools for glycobiology. One approach toward constructing such molecules involves chemical glycosylation of aldehyde-tagged proteins. Here, we report the installation of a genetically encoded aldehyde tag at the internal glycosylation site of the crystallizable fragment (Fc) of IgG1. We replaced the natural Fc N-glycosylation sequon with a five amino-acid sequence that was efficiently converted by recombinant formylglycine generating enzyme in vitro, thereby introducing aldehyde groups for subsequent chemical elaboration. Oxime-linked glycoconjugates were synthesized by conjugating aminooxy N-acetylglucosamine to the modified Fc followed by enzymatic transfer of complex N-glycans from corresponding glycan oxazolines by an EndoS-derived glycosynthase. In this manner we generated specific Fc glycoforms without relying on natural protein glycosylation machineries.

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Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags

Smith

Giddens

Iavarone³

et al. 2014

Bioconjugate Chem.

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“…The targeting of highly nucleophilic cysteines either naturally occurring or genetically installed at the protein surface is another employed approach. Indeed, thiols can react rapidly with a wide range of sugar derivatives appended with electrophilic functional groups [116]. Tyrosine residues are less abundant (and usually less exposed) than lysine, and hence, they are optimal targets for site-selective glycoconjugation [117].…”

Section: Protein-based Glycoconjugatesmentioning

confidence: 99%

Recent advances on smart glycoconjugate vaccines in infections and cancer

et al. 2021

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“…Seine Arbeitsgruppe untersucht die Chemie, chemische Biologie und Biotechnologie von Kohlenhydraten und Proteinen, einschließlich Biokatalyse, Enzymmechanismen, Protein‐Engineering und Wirkstofftransport. Seine jüngste Zuschrift in der Angewandten Chemie beschreibt die Herstellung von Glycokonjugat‐Impfstoffen 2a. Davis war bereits in der Rubrik Autorenprofile vertreten 2b…”

Section: Ausgezeichnet …︁unclassified

Glycosylated Star‐Shaped Conjugated Oligomers for Targeted Two‐Photon Fluorescence Imaging

Wang

Zhang

Geng

et al. 2012

Chemistry A European J

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A glucopyranose functionalized star-shaped oligomer, N-tris{4,4',4''-[(1E)-2-(2-{(E)-2-[4-(benzo[d]thiazol-2-yl)phenyl]vinyl}-9,9-bis(6-2-amido-2-deoxy-1-thio-β-D-glucopyranose-hexyl)-9H-fluoren-7-yl)vinyl]phenyl}phenylamine (TVFVBN-S-NH(2)), is synthesized for two-photon fluorescence imaging. In water, TVFVBN-S-NH(2) self-assembles into nanoparticles with an average diameter of ∼49 nm and shows a fluorescence quantum yield of 0.21. Two-photon fluorescence measurements reveal that TVFVBN-S-NH(2) has a two-photon absorption cross-section of ∼1100 GM at 780 nm in water. The active amine group on the glucopyranose moiety allows further functionalization of TVFVBN-S-NH(2) with folic acid to yield TVFVBN-S-NH(2) FA with similar optical and physical properties as those for TVFVBN-S-NH(2). Cellular imaging studies reveal that TVFVBN-S-NH(2) FA has increased uptake by MCF-7 cells relative to that for TVFVBN-S-NH(2), due to specific interactions between folic acid and folate receptors on the MCF-7 cell membrane. This study demonstrates the effectiveness of glycosylation as a molecular engineering strategy to yield water-soluble materials with a large two-photon absorption (TPA) cross-section for targeted cancer-cell imaging.

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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 16 publications

References 48 publications

Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags

Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags

Recent advances on smart glycoconjugate vaccines in infections and cancer

Glycosylated Star‐Shaped Conjugated Oligomers for Targeted Two‐Photon Fluorescence Imaging

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