The Experts below are selected from a list of 1404 Experts worldwide ranked by ideXlab platform
Gaojian Chen - One of the best experts on this subject based on the ideXlab platform.
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take immune cells back on track Glycopolymer engineered tumor cells for triggering immune response
ACS Macro Letters, 2019Co-Authors: Qi Liu, Gaojian Chen, Shuaibing Jiang, Bing Liu, Zhen-ao Zhao, Chao Wang, Zhuang Liu, Hong ChenAbstract:The “self-homing” of cancer cells to primary or metastatic tumor sites indicates that they could serve as vehicles for self-targeted cancer therapy; this suggests a promising method for treating end-stage cancer. Inspired by this, we propose that engineering cancer cells to carry efficient “coup” molecules for in situ activation of immune cells in or near tumor sites to attack tumors is a promising strategy for cancer therapy. Therefore, herein we explored the potential of engineered tumor cells to enhance their anticancer activity by stimulating immune cells. We armed tumor cell surfaces with specific Glycopolymer–ligands that bind to lectins on macrophages or dendritic cells by combining HaloTag protein (HTP) fusion technique with reversible addition–fragmentation chain transfer (RAFT) polymerization. We demonstrated that two synthetic well-defined Glycopolymers containing, respectively, N-acetylglucosamine and N-acetylmannosamine units, were introduced and stably presented on the cell surfaces via the ...
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Take Immune Cells Back on Track: Glycopolymer-Engineered Tumor Cells for Triggering Immune Response
2019Co-Authors: Qi Liu, Gaojian Chen, Shuaibing Jiang, Bing Liu, Zhen-ao Zhao, Chao Wang, Zhuang Liu, Hong ChenAbstract:The “self-homing” of cancer cells to primary or metastatic tumor sites indicates that they could serve as vehicles for self-targeted cancer therapy; this suggests a promising method for treating end-stage cancer. Inspired by this, we propose that engineering cancer cells to carry efficient “coup” molecules for in situ activation of immune cells in or near tumor sites to attack tumors is a promising strategy for cancer therapy. Therefore, herein we explored the potential of engineered tumor cells to enhance their anticancer activity by stimulating immune cells. We armed tumor cell surfaces with specific Glycopolymer–ligands that bind to lectins on macrophages or dendritic cells by combining HaloTag protein (HTP) fusion technique with reversible addition–fragmentation chain transfer (RAFT) polymerization. We demonstrated that two synthetic well-defined Glycopolymers containing, respectively, N-acetylglucosamine and N-acetylmannosamine units, were introduced and stably presented on the cell surfaces via the stable covalent binding of chloroalkane-terminated polymers with membrane-bound HTP. Furthermore, it was shown that the Glycopolymer-engineered HeLa cells with HTP anchors increased expression of the typical marker for M1-type macrophages (CD86) and upregulated secretion of pro-inflammatory cytokines (IL-12p70, TNF-α, and iNOS), thereby accelerating HeLa cell lysis. The maturation of dendritic cells was also promoted. This study demonstrates the strong potential of Glycopolymer-engineered tumor cells in cancer immunotherapy
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Sunlight-Induced RAFT Synthesis of Multifaceted Glycopolymers with Surface Anchoring, In Situ AgNP Formation, and Antibacterial Properties
2018Co-Authors: Lun Peng, Weidong Zhang, Yan Luo, Yuqing Zheng, Gaojian ChenAbstract:A multifaceted Glycopolymer is designed for the convenient and universal fabrication of antibacterial surfaces. Sunlight-induced living-radical polymerization in the presence of a reversible addition–fragmentation chain-transfer agent without a photoinitiator was applied to obtain well-designed multifunctional Glycopolymers containing three functional groups that can complex with a silver ion, bind to different surfaces, and form silver nanoparticles in situ. The polymerization behavior and the effects of the concentration of the three monomers have been investigated. The obtained polymers can be used to effectively modify a variety of surfaces [silicon wafer, poly(dimethylsiloxane), and stainless steel] and the modification is characterized by contact-angle studies, Fourier transform infrared, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy. In addition, the effect of the composition of the polymers on the antibacterial properties of different surfaces has been studied
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Synthetic Glycopolymers for Highly Efficient Differentiation of Embryonic Stem Cells into Neurons: Lipo- or Not?
2017Co-Authors: Qi Liu, Gaojian Chen, Zhen-ao Zhao, Zhonglin Lyu, Lin Yuan, Hong ChenAbstract:To realize the potential application of embryonic stem cells (ESCs) for the treatment of neurodegenerative diseases, it is a prerequisite to develop an effective strategy for the neural differentiation of ESCs so as to obtain adequate amount of neurons. Considering the efficacy of glycosaminoglycans (GAG) and their disadvantages (e.g., structure heterogeneity and impurity), GAG-mimicking Glycopolymers (designed polymers containing functional units similar to natural GAG) with or without phospholipid groups were synthesized in the present work and their ability to promote neural differentiation of mouse ESCs (mESCs) was investigated. It was found that the lipid-anchored GAG-mimicking Glycopolymers (lipo-pSGF) retained on the membrane of mESCs rather than being internalized by cells after 1 h of incubation. Besides, lipo-pSGF showed better activity in promoting neural differentiation. The expression of the neural-specific maker β3-tubulin in lipo-pSGF-treated cells was ∼3.8- and ∼1.9-fold higher compared to natural heparin- and pSGF-treated cells at day 14. The likely mechanism involved in lipo-pSGF-mediated neural differentiation was further investigated by analyzing its effect on fibroblast growth factor 2 (FGF2)-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway which is important for neural differentiation of ESCs. Lipo-pSGF was found to efficiently bind FGF2 and enhance the phosphorylation of ERK1/2, thus promoting neural differentiation. These findings demonstrated that engineering of cell surface glycan using our synthetic lipo-Glycopolymer is a highly efficient approach for neural differentiation of ESCs and this strategy can be applied for the regulation of other cellular activities mediated by cell membrane receptors
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Glycopolymer based nanoparticles synthesis and application
Polymer Chemistry, 2015Co-Authors: Gaojian ChenAbstract:Synthetic Glycopolymers with pendent sugar moieties are able to interact with lectins as multivalent ligands in a similar manner to natural glycoproteins. Nanoparticles (NPs), due to their small size and high surface/volume ratio, lead to very different properties compared with bulk-matter, and NPs have shown great potential in nanomedicine and other biological applications. NPs with Glycopolymers on the surface are one of the desirable bio-active particles and an important material to investigate. This review focuses on the synthesis of various Glycopolymer-based nanoparticles via different approaches such as self-assembly and the preparation of Glycopolymer-conjugated inorganic NPs, and their different applications.
Remzi C Becer - One of the best experts on this subject based on the ideXlab platform.
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single chain Glycopolymer folding via host guest interactions and its unprecedented effect on dc sign binding
Biomacromolecules, 2018Co-Authors: Gokhan Yilmaz, Veselina Uzunova, Richard M Napier, Remzi C BecerAbstract:Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded Glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host–guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition–fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of Glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR an...
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Single-Chain Glycopolymer Folding via Host–Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding
2018Co-Authors: Gokhan Yilmaz, Veselina Uzunova, Richard Napier, Remzi C BecerAbstract:Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded Glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host–guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition–fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of Glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures
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sequence and architectural control in Glycopolymer synthesis
Macromolecular Rapid Communications, 2017Co-Authors: Yamin Abdouni, Gokhan Yilmaz, Remzi C BecerAbstract:Glycopolymers are synthetic-carbohydrate-containing materials capable of interacting and binding to specific targeting lectins, which are crucially important in many biologically active processes. Over the last decade, advances in synthetic chemistry and polymerization techniques have enabled the development of sequence and architecturally controlled Glycopolymers for different types of bioapplications, such as drug delivery and release purposes, gene therapy, lectin-based biosensors, and much more in the future. These precision Glycopolymers are able to mimic structural and functional features of the naturally existing glycocalyx. Furthermore, self-assembled Glycopolymers could enhance specific and selective recognition properties on multivalent scaffolds in glycoscience. This mini-review will focus on production methods and recent advances in precision synthesis and self-assembly of Glycopolymers. Additionally, possible contributions of single-chain folding in Glycopolymers will be discussed as a future prospect.
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the Glycopolymer code synthesis of Glycopolymers and multivalent carbohydrate lectin interactions
Macromolecular Rapid Communications, 2012Co-Authors: Remzi C BecerAbstract:Glycopolymers are becoming more and more important in understanding biological interactions due to their unique recognition properties. Macromolecules with different chain lengths, compositions and architectures provide enormous diversity in the formation of primary and secondary structures that have a major effect on multivalent binding to lectins. It is crucial to control the precise structure of macromolecules to achieve specific and selective carbohydrate-lectin binding. The use of advanced synthesis techniques to prepare well-defined Glycopolymers and selected advanced analytical techniques to study multivalent interactions are highlighted in this Feature Article.
Changming Dong - One of the best experts on this subject based on the ideXlab platform.
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star shaped polypeptide Glycopolymer biohybrids synthesis self assembly biomolecular recognition and controlled drug release behavior
Journal of Polymer Science Part A, 2009Co-Authors: Shuo Qiu, Hui Huang, Wei Zhou, Xiaohui Dai, Changming DongAbstract:Star-shaped polypeptide/Glycopolymer biohybrids composed of poly(γ- benzyl L-glutamate) and poly(D-gluconamidoethyl methacrylate), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride and the direct atom transfer radical polymerization of unprotected D-gluconamidoethyl methacrylate glycomonomer. These biohybrids were characterized in detail by means of FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X-ray diffraction. Independent of weight fraction of hydrophilic Glycopolymer segment, the biohybrids self-assembled into large spherical micelles in aqueous solution, which had a helical polypeptide core surrounded by a multivalent Glycopolymer shell. The deprotected poly(L-glutamate)/Glycopolymer hybrid exhibited a pH-sensitive self-assembly behavior, and the average size of the nanoparticles decreased gradually over the aqueous pH value. Moreover, whatever these biohybrids existed in unimolecular level or Glycopolymer-surfaced nanoparticles, they had specific biomolecular recognition with Concanavalin A compared with bovine serum albumin. Furthermore, star-shaped biohybrids showed a higher doxorubicin loading efficiency and longer drug-release time than linear analogues. This potentially provides a platform for fabricating targeted anticancer drug delivery system and studying glycoprotein functions in vitro. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2009–2023, 2009
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star shaped polypeptide Glycopolymer biohybrids synthesis self assembly biomolecular recognition and controlled drug release behavior part a polymer chemistry
Journal of Polymer Science, 2009Co-Authors: Shuo Qiu, Hui Huang, Wei Zhou, Xiaohui Dai, Changming DongAbstract:Star-shaped polypeptide/Glycopolymer biohybrids composed of poly(γ- benzyl L-glutamate) and poly(D-gluconamidoethyl methacrylate), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride and the direct atom transfer radical polymerization of unprotected D-gluconamidoethyl methacrylate glycomonomer. These biohybrids were characterized in detail by means of FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X-ray diffraction. Independent of weight fraction of hydrophilic Glycopolymer segment, the biohybrids self-assembled into large spherical micelles in aqueous solution, which had a helical polypeptide core surrounded by a multivalent Glycopolymer shell. The deprotected poly(L-glutamate)/Glycopolymer hybrid exhibited a pH-sensitive self-assembly behavior, and the average size of the nanoparticles decreased gradually over the aqueous pH value. Moreover, whatever these biohybrids existed in unimolecular level or Glycopolymer-surfaced nanoparticles, they had specific biomolecular recognition with Concanavalin A compared with bovine serum albumin. Furthermore, star-shaped biohybrids showed a higher doxorubicin loading efficiency and longer drug-release time than linear analogues. This potentially provides a platform for fabricating targeted anticancer drug delivery system and studying glycoprotein functions in vitro.
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supramolecular and biomimetic polypseudorotaxane Glycopolymer biohybrids synthesis glucose surfaced nanoparticles and recognition with lectin
Journal of Physical Chemistry B, 2008Co-Authors: Xiaohui Dai, Changming Dong, Deyue YanAbstract:A new class of supramolecular and biomimetic Glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/Glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic Glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of Glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/Glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.
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synthesis and characterization of Glycopolymer polypeptide triblock copolymers
Biomacromolecules, 2004Co-Authors: Changming Dong, Xue-long Sun, Keith M Faucher, Robert P Apkarian, Elliot L. ChaikofAbstract:Glycopolymer-polypeptide triblock copolymers of the structure, poly(l-alanine)-b-poly(2-acryloyloxyethyl-lactoside)-b-poly(l-alanine) (AGA), have been synthesized by sequential atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyl-oxyethoxyl-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)−(1-4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy complex system was used to generate a central Glycopolymer block. Telechelic Glycopolymers with diamino end groups were obtained by end group transformation and subsequently used as macroinitiators for ROP of l-alanine N-carboxyanhydride monomers (Ala−NCA). Gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular weight and composition were controlled by both the molar ratios of the Ala−NCA monomer to macroinitiator and monomer conversion and exhibited a narrow distributi...
Gokhan Yilmaz - One of the best experts on this subject based on the ideXlab platform.
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synthesis of brush like Glycopolymers with monodisperse sequence defined side chains and their interactions with plant and animal lectins
Macromolecular Rapid Communications, 2020Co-Authors: Fadi Shamout, Alessandra Monaco, Gokhan Yilmaz, Caglar Remzi Becer, Laura HartmannAbstract:: The synthesis of brush Glycopolymers mimicking the architecture of proteoglycans is achieved by grafting sequence-defined glycooligomers derived from solid-phase polymer synthesis onto a poly(active ester) scaffold. This approach gives access to a first library of brush Glycopolymers with controlled variations in the degree of branching and number of carbohydrate ligands per branch. When studying lectin binding of linear and brush Glycopolymers to lectins Concanavalin A (ConA), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and mannose-binding lectin (MBL), different preferences are observed with MBL showing higher binding to linear Glycopolymer and ConA and DC-SIGN favoring brush Glycopolymers. This finding suggests that the architecture of polymeric glycan mimetics affects binding to lectins not only in terms of creating higher avidity but potentially also selectivity ligands.
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single chain Glycopolymer folding via host guest interactions and its unprecedented effect on dc sign binding
Biomacromolecules, 2018Co-Authors: Gokhan Yilmaz, Veselina Uzunova, Richard M Napier, Remzi C BecerAbstract:Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded Glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host–guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition–fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of Glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR an...
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ph responsive Glycopolymer nanoparticles for targeted delivery of anti cancer drugs
Molecular Systems Design & Engineering, 2018Co-Authors: Gokhan Yilmaz, Emine Guler, Caner Geyik, Bilal Demir, Melek Ozkan, Dilek Odaci Demirkol, Serdar Ozcelik, Suna TimurAbstract:Over the past decade, there has been a great deal of interest in the integration of nanotechnology and carbohydrates. The advances in glyconanotechnology have allowed the creation of different bioactive glyconanostructures for different types of medical applications, especially for drug delivery and release systems. Therefore, the use of more efficient biocompatible nanocarriers with high loading capacity, low overall toxicity and receptor-mediated endocytosis specificity is still in focus for the enhancement of the therapeutic effect. Conjugation of sugar derivatives onto gold nanoparticles presents unique properties that include a wide array of assembling models and size-related electronic, magnetic and optical properties. Here, pH-responsive drug-conjugated Glycopolymer-coated gold nanoparticles were prepared by functionalization of gold nanoparticles with thiol-terminated Glycopolymers and then subsequent conjugation of doxorubicin (DOX). Among the four different Glycopolymers, their drug release, physicochemical characterization (spectroscopy, particle size and surface charge) and in vitro bioapplications with four different cell lines were compared. As a result, pH-sensitive drug delivery via sugar-coated AuNPs was performed thanks to hydrazone linkages between Glycopolymers and DOX. Comparative viability tests also demonstrated the efficiency of Glycopolymer–DOX conjugates by fluorescence cell imaging. The obtained results reveal that AuNP homoGlycopolymer DOX conjugates (P4D) have significant potential, especially in human neuroblastoma cells in comparison to cervical cancer cells and lung cancer cells.
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Single-Chain Glycopolymer Folding via Host–Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding
2018Co-Authors: Gokhan Yilmaz, Veselina Uzunova, Richard Napier, Remzi C BecerAbstract:Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded Glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host–guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition–fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of Glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures
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sequence and architectural control in Glycopolymer synthesis
Macromolecular Rapid Communications, 2017Co-Authors: Yamin Abdouni, Gokhan Yilmaz, Remzi C BecerAbstract:Glycopolymers are synthetic-carbohydrate-containing materials capable of interacting and binding to specific targeting lectins, which are crucially important in many biologically active processes. Over the last decade, advances in synthetic chemistry and polymerization techniques have enabled the development of sequence and architecturally controlled Glycopolymers for different types of bioapplications, such as drug delivery and release purposes, gene therapy, lectin-based biosensors, and much more in the future. These precision Glycopolymers are able to mimic structural and functional features of the naturally existing glycocalyx. Furthermore, self-assembled Glycopolymers could enhance specific and selective recognition properties on multivalent scaffolds in glycoscience. This mini-review will focus on production methods and recent advances in precision synthesis and self-assembly of Glycopolymers. Additionally, possible contributions of single-chain folding in Glycopolymers will be discussed as a future prospect.
David M. Haddleton - One of the best experts on this subject based on the ideXlab platform.
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Engineered Hydrogen-Bonded Glycopolymer Capsules and Their Interactions with Antigen Presenting Cells
ACS Applied Materials and Interfaces, 2017Co-Authors: Kristian Kempe, Md Arifur Rahim, Sue D. Xiang, Michael R Whittaker, Magdalena Plebanski, Yi Ju, Frank Caruso, David M. Haddleton, Paul Wilson, Thomas P DavisAbstract:Hollow Glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The Glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Multilayer assembly of the hydrogen-bonding pair (Glycopolymer/poly(methacrylic acid) (PMA)) onto planar and particulate supports (SiO2 particles, d = 1.16 μm) yielded stable Glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) particle templates were removed yielding hollow monodisperse capsules, as demonstrated by fluorescence and scanning electron microscopy. Cellular uptake studies us...
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from polymer sequence control to protein recognition synthesis self assembly and lectin binding
Macromolecules, 2014Co-Authors: Shiqi Wang, David M. Haddleton, Gaojian Chen, Lei Tao, Litang Yan, Yen WeiAbstract:A novel, highly efficient methodology to synthesize gradient Glycopolymers has been successfully developed involving concurrent enzymatic monomer transformation and reversible addition–fragmentation chain transfer (RAFT) polymerization. By synchronizing enzymatic monomer transformation with polymerization, a continuous supply of the second monomer (glycomonomer) is achieved during the polymerization, resulting in a gradient sugar distribution in the final polymer. Detailed studies of the process using GPC and NMR indicate that the gradient Glycopolymers synthesized by RAFT were well controlled. Subsequently, 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-α-d-galactopyranose (DIMAG) moieties were deprotected to regenerate the sugar and achieve amphiphilic bioactive Glycopolymers. We demonstrate the synthesis of a set of Glycopolymers with different sequential structures, such as statistical, gradient and block Glycopolymers. The Glycopolymers with block structure show higher affinities toward the RCA120 lect...
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Glycopolymers with secondary binding motifs mimic glycan branching and display bacterial lectin selectivity in addition to affinity
Chemical Science, 2014Co-Authors: Mathew W Jones, David M. Haddleton, Lucienne Otten, Sarahjane Richards, Richard Lowery, Daniel J Phillips, Matthew I. GibsonAbstract:The application of synthetic Glycopolymers to anti-adhesive therapies has so far been limited by their lack of lectin specificity. Here we employ a macromolecular engineering approach to mimic glycan architecture. A new, 3-step tandem post-polymerisation methodology was developed which afforded precise control over both chain length and carbohydrate (galactose)-polymer backbone linker distance. This route also allowed a secondary binding (branched) motif to be introduced onto the linker, increasing specificity and affinity towards bacterial toxins without the need for extensive carbohydrate or organic chemistry. Sequential variation of this motif was found to dramatically alter both the affinity and the specificity of the Glycopolymers towards two lectins, CTx and PNA, by up to 20-fold either via direct binding, or increased steric constraints. Using this method, a Glycopolymer that showed increased specificity towards CTx was identified.
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High-affinity Glycopolymer binding to human DC-SIGN and disruption of DC-SIGN interactions with HIV envelope glycoprotein
Journal of the American Chemical Society, 2010Co-Authors: C. Remzi Becer, R Wallis, Daniel A. Mitchell, Jin Geng, Matthew I. Gibson, Rebecca Ilyas, David M. HaddletonAbstract:Noncovalent interactions between complex carbohydrates and proteins drive many fundamental processes within biological systems, including human immunity. In this report we aimed to investigate the potential of mannose-containing Glycopolymers to interact with human DC-SIGN and the ability of these Glycopolymers to inhibit the interactions between DC-SIGN and the HIV envelope glycoprotein gp120. We used a library of Glycopolymers that are prepared via combination of copper-mediated living radical polymerization and azide-alkyne [3+2] Huisgen cycloaddition reaction. We demonstrate that a relatively simple Glycopolymer can effectively prevent the interactions between a human dendritic cell associated lectin (DC-SIGN) and the viral envelope glycoprotein gp120. This approach may give rise to novel insights into the mechanisms of HIV infection and provide potential new therapeutics.