Synthesis of Glycoproteins

Davis, Benjamin G.

doi:10.1021/cr0004310

Cited by 499 publications

(280 citation statements)

References 279 publications

(551 reference statements)

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“…Among the several methods available for the construction of glycoproteins (29), chemical glycosylation offers advantages, such as precise control of sugar and ease of scale-up, and affords straightforward access to well defined glycoproteins. Lysine groups in N-WT and N-DG were chemically glycosylated by using the IME method (20,21).…”

Section: Resultsmentioning

confidence: 99%

LEAPT: Lectin-directed enzyme-activated prodrug therapy

Robinson

Charlton

Garnier

et al. 2004

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

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. We describe a bipartite drug-delivery system that exploits (i) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conjugates to specific, predetermined cell types followed by (ii) administration of a prodrug activated by that predelivered enzyme at the desired site. The carbohydrate structure of an ␣-L-rhamnopyranosidase enzyme was specifically engineered through enzymatic deglycosylation and chemical reglycosylation. Combined in vivo and in vitro techniques (gamma scintigraphy, microautoradiography and confocal microscopy) determined organ and cellular localization and demonstrated successful activation of ␣-L-rhamnopyranoside prodrug. Ligand competition experiments revealed enhanced, specific localization by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in selectivity toward target cell hepatocytes that generated a >30-fold increase (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation engineering enhanced the serum-uptake rate and enzyme stability. This created enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of which was switched simply by sugar-type alteration. The therapeutic effectiveness of lectin-directed enzymeactivated prodrug therapy was shown through the construction of the prodrug of doxorubicin, Rha-DOX, and its application to reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.

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Section: Resultsmentioning

confidence: 99%

LEAPT: Lectin-directed enzyme-activated prodrug therapy

Robinson

Charlton

Garnier

et al. 2004

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

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“…Indeed, the failure of a number of carbohydrate-based drugs may be attributed to a poor understanding of their supposed mechanism of action rather than to any inherent deficiency of carbohydrate therapeutics. 61 When good understanding is achieved, the results are impressive. 105,107…”

Section: Discussionmentioning

confidence: 99%

“…The reason for this weakness lies in the solvent-exposed nature of the lectin binding-sites, which are shallow pockets making few direct contacts with the ligands. 61 There is, in fact, a significant difference in affinity between these shallow sites and deep sites, as is well illustrated by the influenza haemagglutinin lectin, which binds sialic acids with an approximately 1000-fold lower affinity than a neuraminidase found in the same virus. 62 Nevertheless, lectins exhibit both high affinity and exquisite specificity for oligosaccharide structures of glycoproteins and glycolipids on the cell surface.…”

Section: Multivalencymentioning

confidence: 99%

Lectins: Tools for the Molecular Understanding of the Glycocode

2005

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Recent progress in glycobiology has revealed that cell surface oligosaccharides play an essential role in recognition events. More precisely, these saccharides may be complexed by lectins, carbohydrate-binding proteins other than enzymes and antibodies, able to recognise sugars in a highly specific manner. The ubiquity of lectin-carbohydrate interactions opens enormous potential for their exploitation in BA (1993) and DPhil (1996) T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y

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“…For this aim, a vast array of unnatural glycoconjugates (neoglycoconjugates) with different valencies and spatial arrangement of the ligand have been constructed as sugar binding proteins antagonist to prevent or treat diseases caused by pathogens . Scaffolds based on peptides and proteins (Davis, 2002;Payne, Wong, 2010;Westerlind, 2012), polymers (Miura, 2012;Eissa, Cameron, 2013), calixarenes (Baldini, et al, 2007;Dondoni, Marra, 2010), dendrimers (Li, Cheng, Xu, 2007;Chabre, Roy, 2008), cyclodextrins (Fulton, Stoddart, 2001;Gomez-Garcia, 2012;Martínez, Ortíz Mellet, García Fernández, 2013), cyclopeptides (Galan, Dumy, Renaudet, 2013), fullerenes (Nierengarten, 2010), gold nanoparticles and quantum dots (El-Boubbou, 2011;Marradi et al, 2013) provide nanoscale materials with anti-adhesive and cell targeting properties.…”

Section: Introductionmentioning

confidence: 99%

Glycodendritic structures: tools to interact with DC-SIGN

Reina

Rojo

2013

Braz. J. Pharm. Sci.

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The key role of carbohydrates in many biological events has attracted the interest of the scientific community. This fact has demanded the access to new tools necessary to understand this role and the interaction of carbohydrates with their corresponding receptors, lectins. Glycodendrimers and glycodendritic structures in general, have demonstrated to be very efficient and interesting tools to intervene in those processes where carbohydrates participate. In this review, we discuss the different glycodendritic structures that have been used to interfere with DC-SIGN, a very attractive lectin involved in infection processes and in the regulation of the immune response.

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Synthesis of Glycoproteins

Cited by 499 publications

References 279 publications

LEAPT: Lectin-directed enzyme-activated prodrug therapy

LEAPT: Lectin-directed enzyme-activated prodrug therapy

Lectins: Tools for the Molecular Understanding of the Glycocode

Glycodendritic structures: tools to interact with DC-SIGN

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