Hierarchical Assembly of Model Cell Surfaces:  Synthesis of Mucin Mimetic Polymers and Their Display on Supported Bilayers

Rabuka, David; Parthasarathy, Raghuveer; Lee, Goo Soo; Chen, Xing; Groves, Jay T.; Bertozzi, Carolyn R.

doi:10.1021/ja067819i

Cited by 51 publications

(59 citation statements)

References 35 publications

(33 reference statements)

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“…17 Importantly, the modified CNTs were nontoxic to cultured cells. These findings were tempered, however, by the irregular surface and nonuniform thickness of the CNT coating, which reflected the high polydispersities (>1.7) of the polymers employed 18. Such surface heterogeneity might undermine the use of glycopolymer‐coated CNTs as sensors of protein binding.…”

Section: Methodsmentioning

confidence: 99%

Biocompatible Carbon Nanotubes Generated by Functionalization with Glycodendrimers

Chen

et al. 2008

Angew Chem Int Ed

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171

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Protective coatings: Glycodendrimers can function as homogeneous bioactive coatings that mitigate the cytotoxicity of single‐walled carbon nanotubes (SWNTs). The bifunctional glycodendrimers (see picture) have peripheral carbohydrate units and a pyrene tail capable of binding SWNT surfaces through π–π interaction. Cells cultured with glycodendrimer‐coated SWNTs proliferate at the same rate as untreated cells.

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Section: Methodsmentioning

confidence: 99%

Biocompatible Carbon Nanotubes Generated by Functionalization with Glycodendrimers

Chen

et al. 2008

Angew Chem Int Ed

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171

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“…26e On other the hand, Bertozzi and coworkers conjugated 28 to a polymer scaffold containing pendant ketone to generate 30 (Scheme 5) for use to mimic the MUC1 mucin of epithelial cells. 27 …”

Section: Resultsmentioning

confidence: 99%

Utilization of bench-stable and readily available nickel(II) triflate for access to 1,2-cis-2-aminoglycosides

Sletten

Ramadugu

Nguyen

2016

Carbohydrate Research

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The utilization of substoichiometric amounts of commercially available nickel(II) triflate as an activator in the reagent-controlled glycosylation reaction for the stereoselective construction of biologically relevant targets containing 1,2-cis-2-amino glycosidic linkages is reported. This straightforward and accessible methodology is mild, operationally simple and safe through catalytic activation by readily available Ni(OTf)2 in comparison to systems employing our previously in-house prepared Ni(4-F-PhCN)4(OTf)2. We anticipate that the bench-stable and inexpensive Ni(OTf)2, coupled with little to no extra laboratory training to set up the glycosylation reaction and no requirement of specialized equipment, should make this methodology be readily adopted by non-carbohydrate specialists. This report further highlights the efficacy of Ni(OTf)2 to prepare several bioactive motifs, such as blood type A-type V and VI antigens, heparin sulfate disaccharide repeating unit, aminooxy glycosides, and α-GalNAc-Serine conjugate, which cannot be achieved in high yield and α-selectivity utilizing in-house prepared Ni(4-F-PhCN)4(OTf)2 catalyst. The newly-developed protocol eliminates the need for the synthesis of Ni(4-F-PhCN)4(OTf)2 and is scalable and reproducible. Furthermore, computational simulations in combination with 1H NMR studies analyzed the effects of various solvents on the intramolecular hydrogen bonding network of tumor-associated mucin Fmoc-protected GalNAc-threonine amino acid antigen derivative, verifying discrepancies found that were previously unreported.

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“…Artificial mucin-like glycoconjugates mimicking their natural counterparts have been designed by adding carbohydrates to synthetically tractable polymer backbones. These large backbones are then linked to a terminal hydrophobic phospholipid tail for anchoring into lipid bilayers [23], [24]. Here, we evaluated whether fluorescent glycopolymers with a lipid anchor and chain-length distributions of 30 and 80 nm (corresponding to 240 and 640 repeating units, respectively) could be inserted into cultures of stratified human corneal epithelial cells to modify the character of the cell surface.…”

Section: Resultsmentioning

confidence: 99%

Modulation of Ocular Surface Glycocalyx Barrier Function by a Galectin-3 N-terminal Deletion Mutant and Membrane-Anchored Synthetic Glycopolymers

et al. 2013

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BackgroundInteraction of transmembrane mucins with the multivalent carbohydrate-binding protein galectin-3 is critical to maintaining the integrity of the ocular surface epithelial glycocalyx. This study aimed to determine whether disruption of galectin-3 multimerization and insertion of synthetic glycopolymers in the plasma membrane could be used to modulate glycocalyx barrier function in corneal epithelial cells.Methodology/Principal FindingsAbrogation of galectin-3 biosynthesis in multilayered cultures of human corneal epithelial cells using siRNA, and in galectin-3 null mice, resulted in significant loss of corneal barrier function, as indicated by increased permeability to the rose bengal diagnostic dye. Addition of β-lactose, a competitive carbohydrate inhibitor of galectin-3 binding activity, to the cell culture system, transiently disrupted barrier function. In these experiments, treatment with a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, but not full-length galectin-3, prevented the recovery of barrier function to basal levels. As determined by fluorescence microscopy, both cellobiose- and lactose-containing glycopolymers incorporated into apical membranes of corneal epithelial cells, independently of the chain length distribution of the densely glycosylated, polymeric backbones. Membrane incorporation of cellobiose glycopolymers impaired barrier function in corneal epithelial cells, contrary to their lactose-containing counterparts, which bound to galectin-3 in pull-down assays.Conclusions/SignificanceThese results indicate that galectin-3 multimerization and surface recognition of lactosyl residues is required to maintain glycocalyx barrier function at the ocular surface. Transient modification of galectin-3 binding could be therapeutically used to enhance the efficiency of topical drug delivery.

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Hierarchical Assembly of Model Cell Surfaces: Synthesis of Mucin Mimetic Polymers and Their Display on Supported Bilayers

Cited by 51 publications

References 35 publications

Biocompatible Carbon Nanotubes Generated by Functionalization with Glycodendrimers

Biocompatible Carbon Nanotubes Generated by Functionalization with Glycodendrimers

Utilization of bench-stable and readily available nickel(II) triflate for access to 1,2-cis-2-aminoglycosides

Modulation of Ocular Surface Glycocalyx Barrier Function by a Galectin-3 N-terminal Deletion Mutant and Membrane-Anchored Synthetic Glycopolymers

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