Receptor Mediated Glycotargeting

Wadhwa, Manpreet S.; Rice, Kevin G.

doi:10.3109/10611869509059211

Cited by 102 publications

(39 citation statements)

References 152 publications

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“…Carbohydrate recognition-based TDGD has been applied broadly for decades, and glycotargeting could be a powerful strategy for treating immune disorders [80]. Developments in glycobiology and nanotechnology have facilitated the extensive application of carbohydrate-decorated TDGD systems [81].…”

Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

Targeting Neutrophils in Severe Asthma via Siglec-9

Chen

Bai

Han

et al. 2018

Int Arch Allergy Immunol

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Severe asthma comprises only 5% of patients with asthma, but the burden it brings to the social health system accounts for more than half of all asthmatics. Clinical evidence shows that severe asthma is often linked to the recruitment and activation of neutrophils in the airways. However, the underlying molecular and immunological mechanisms of neutrophilia in severe asthma are not clear and currently available drugs exert only limited effects on neutrophilic inflammation. Great efforts are underway to address the mystery of neutrophilic inflammation in chronic respiratory disorders. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are members of the immunoglobulin gene family. Of note, Siglec-9 is uniquely expressed by human neutrophils and monocytes, as well as a minor population of natural killer cells. Engaging this structure with antibodies or glycan ligands results in programmed cell death in human neutrophils. Intriguingly, the administration of Siglec-E antibody abolished the recruitment of neutrophils in mouse models of neutrophilic pulmonary inflammation in vivo. Given that neutrophils are probably a major culprit in the generation and perpetuation of inflammation, targeting Siglec-9 could be beneficial for the treatment of severe asthma, chronic obstructive pulmonary disease, and related pulmonary disorders characteristic of neutrophilia.

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Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

Targeting Neutrophils in Severe Asthma via Siglec-9

Chen

Bai

Han

et al. 2018

Int Arch Allergy Immunol

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“…This approach offers certain advantages in that only high affinity (K d Ͼ micromole) binding is detected, all receptors with serum exposure are assayed simultaneously, and the exogenous ligand must compete with endogenous ligands, leading to physiologically relevant results that can be directly translated into the design of glycotargeted drug delivery systems (24).…”

mentioning

confidence: 99%

Tissue Targeting of Multivalent LeX-terminated N-Linked Oligosaccharides in Mice

Chiu

Thomas

Stubbs

et al. 1995

Journal of Biological Chemistry

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The target site for N-linked biantennary and triantennary oligosaccharides containing multiple terminal Le X determinants was analyzed in mice. N-Linked oligosaccharides containing a single tert-butoxycarbonyl-tyrosine attached to the reducing end were used as synthons for human milk ␣-3/4-fucosyltransferase to prepare multivalent Le X (Gal␤1-4[Fuc␣1-3]GlcNAc) terminated tyrosinamide oligosaccharides. The oligosaccharides were radioiodinated and examined for their pharmacokinetics and biodistribution in mice. The liver was the major target site in mice at 30 min, which accumulated 18% of the dose for Le X biantennary compared with 6% for a nonfucosylated Gal biantennary. By comparison, Le X -and Gal-terminated triantennary accumulated in the liver with a targeting efficiency of 66 and 59%, respectively. The liver targeting of Le X biantennary was partially blocked by co-administration with either galactose or L-fucose whereas Le X triantennary targeting was only reduced by co-administration with galactose. In contrast to these results in mice, in vivo experiments performed in rats established that both Le X and Gal terminated biantennary target the liver with nearly identical efficiency (6 -7%). It is concluded that the asialoglycoprotein receptor in mice preferentially recognize Le X biantennary over Gal biantennary, whereas little or no differentiation exists in rats. Thereby, the mouse asialoglycoprotein receptor apparently possesses additional binding pockets that accommodate a fucose residue when presented as Le X .In mammals, carbohydrate/protein interactions often involve the binding of an oligosaccharide ligand to a cell surface receptor (1, 2). The ligands are most frequently N-or O-linked oligosaccharides that are covalently attached to a glycoprotein. N-Linked oligosaccharides possess a common pentasaccharide core structure which contains a branch point resulting in two or more nonreducing end sugar residues (3). It is often these terminal sugar residues on N-linked oligosaccharides which bind to spatially resolved binding sites on a lectin (4).The mammalian lectins discovered to date have been grouped into several subcategories (5). Several membrane spanning lectins are known to be C-type lectins which contain a carbohydrate recognition domain named for its calcium-dependent ligand binding. Of the C-type lectins, the asialoglycoprotein receptor (ASGP-R) 1 found on hepatocytes has been most thoroughly studied for its binding specificity and its intracellular routing of ligands (6 -8). N-Linked oligosaccharides containing multiple terminal Gal residues bind with high affinity, although GalNAc terminated N-linked oligosaccharides are much more potent ligands (9 -11). A biantennary oligosaccharide possessing only two terminal GalNAc residues is a superior ASGP-R ligand compared with a triantennary possessing three terminal Gal residues (12). In addition to the ASGP-R, several other mammalian lectins have been isolated and characterized in liver. Kupffer cells possess a C-type lectin that binds avidly to ...

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“…Materials covered with a suitable glycopolymer have improved biocompatibility [97,99] and, in the case of nanoparticles, can be targeted to a specific organ [10,247,248]. Examples have already emerged of glycopolymer decorated quantum dots [221], and superparamagnetic iron oxide nanoparticles which may be used for in vivo imaging and hyperthermia treatment [249].…”

Section: Discussionmentioning

confidence: 99%

“…The same polymerization conditions were used to chain extend PEO macro-intiator A3 with M14 in the presence of CuBr(L3) (Entry 83, Table 2) [118]. The resulting PEO 45 -block-polyM14 27 glycopolymer was deprotected and its interaction with ConA was compared to that of polyM14 10 : While both polymers formed aggregates with the lectin, only those from PEO-block-poly(deprotected M14) were stable in water, presumably due to the hydrophilic PEO segments.…”

Section: Methodsmentioning

confidence: 99%

“…This is due to the expectation that polymers displaying carbohydrate functionalities, similar to those of natural glycoconjugates, might be able to mimic, or even exceed, their performance in specific applications (biomimetic approach). More in general, studies have been published on their use of as macromolecular drugs [2][3][4][5][6][7][8], drug delivery systems [9][10][11][12], cell culture substrates [13,14], stationary phase in separation problems [15,16] and bioassays [17]; responsive [18] and catalytic [19] hydrogels, surface modifiers [20][21][22][23], artificial tissues and artificial organ substrates [13].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Glycopolymer Architectures by Reversible-Deactivation Radical Polymerization

Ghadban

Albertin

2013

Polymers

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This review summarizes the state of the art in the synthesis of well-defined glycopolymers by Reversible-Deactivation Radical Polymerization (RDRP) from its inception in 1998 until August 2012. Glycopolymers architectures have been successfully synthesized with four major RDRP techniques: Nitroxide-mediated radical polymerization (NMP), cyanoxyl-mediated radical polymerization (CMRP), atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Over 140 publications were analyzed and their results summarized according to the technique used and the type of monomer(s) and carbohydrates involved. Particular emphasis was placed on the experimental conditions used, the structure obtained (comonomer distribution, topology), the degree of control achieved and the (potential) applications sought. A list of representative examples for each polymerization process can be found in tables placed at the beginning of each section covering a particular RDRP technique.

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Receptor Mediated Glycotargeting

Cited by 102 publications

References 152 publications

Targeting Neutrophils in Severe Asthma via Siglec-9

Targeting Neutrophils in Severe Asthma via Siglec-9

Tissue Targeting of Multivalent LeX-terminated N-Linked Oligosaccharides in Mice

Synthesis of Glycopolymer Architectures by Reversible-Deactivation Radical Polymerization

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