Gokhan Yilmaz

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM: Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments.

Glyconanoparticles and their interactions with lectins

Recent progress in nanobiotechnology has allowed the use of glycans and their conjugates as biofunctional molecules for many biological and biomedical applications. Therefore, specific interactions of carbohydrate-binding proteins (lectins) are continuously being elucidated for a deep understanding of their functions and the precise mechanism of their association with specific ligands. New generations of glyconanoparticles with outstanding features that present carbohydrates in a multivalent manner and locally in high concentrations have been showing promise of establishing the glycan code and functioning as a glycan mimic. In the first part of this review article, different types of lectins have been summarised and their main properties highlighted. In the second part, recent successful examples of glyconanoparticles formed of synthetic polymers and in most cases, conjugated with metals, have been discussed in terms of their synthesis and interactions with lectins.

Block-Sequence-Specific Glycopolypeptides with Selective Lectin Binding Properties

Glycopolypeptides with defined block sequences were prepared by sequential addition of two different N-carboxyanhydrides (NCAs), followed by selective deprotection and functionalization of predefined positions within the polypeptide backbone. The sequential arrangement of the galactose units and the block-sequence length have been systematically varied. All the glycopolypeptides have been obtained with a similar overall composition and comparable molecular weights. Circular dichroism measurements revealed some dependence of the secondary structure on the primary composition of the glycopolypeptides at physiological pH. While statistical, diblock, and tetrablock glycopolypeptides adopted a random coil conformation, the octablock glycopolypeptide was mostly α-helical. The ability to selectively bind to lectins was investigated by turbidity measurements as well as surface plasmon resonance (SPR) studies. It was found that the extent of binding was dependent on the position of the galactose units and thus the primary glycopolypeptide structure. The octablock glycopolypeptide favored interaction with lectin RCA120 while the tetrablock glycopolypeptide demonstrated the strongest binding activity to Galectin-3. The results suggest that different lectins are very sensitive to glyco coding and that precise control of carbohydrate units in synthetic polymeric glycopeptides will remain important.

Glycopolymer Code Based on Well-Defined Glycopolymers or Glyconanomaterials and Their Biomolecular Recognition

Advances in the glycopolymer technology have allowed the preparation of more complex and well-defined glycopolymers/particles with several architectures from linear to globular structures (such as micelles, dendrimers, and nanogels). In the last decade, functionalized self-assembled/decided nano-objects and scaffolds containing glycopolymers were designed to develop many biological and biomedical applications in diseases treatments such as pathogen detection, inhibitors of toxins, and lectin-based biosensors. These studies will facilitate the understanding and investigation of the sugar code on the carbohydrate–lectin interactions, which are significantly influenced by the glycopolymer architecture, valency, size, and density of binding elements. In this context, these advanced and selected glycopolymers/particles showing specific interactions with various lectins are highlighted.

Glyconanoparticles with controlled morphologies and their interactions with a dendritic cell lectin

Well-defined amphiphilic block glycopolymers with equal mannose content have been self-assembled in aqueous solution to form glyconanoparticles with different morphologies. The size and shape of nanoparticles have significant effects on the interactions with the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209), characterized using a surface plasmon resonance spectrometer (SPR).

Sequence and Architectural Control in Glycopolymer Synthesis

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.

pH responsive glycopolymer nanoparticles for targeted delivery of anti-cancer drugs

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.

The effect of linker length on ConA and DC-SIGN binding of S-glucosyl functionalized poly(2-oxazoline)s

A new monomer, 2-[2-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosylthio) propyl)]-2-oxazoline (Ac4Glc-S-Ox), was synthesized by direct addition of 2,3,4,6-Tetra-O-acetyl-1-thio-β-D-glucopyranose (Ac4Glc-SH) to 2-Isopropenyl-2-oxazoline (iPOx) in the presence of solid butyl amine resin via thiol-ene click reaction. The living cationic ring-opening polymerization was performed to prepare copolymers of Ac4Glc-S-Ox with 2-ethyl-2-oxazoline (EtOx). In order to systematically investigate the effect of S-glucosyl substituent linked to the polymer backbone with different linkers on the cloud point and the binding ability, another series of glycopolymers were prepared by post polymerization modification method. Copolymers of 2-decenyl-2-oxazoline and 2-butenyl-2-oxazoline with EtOx were first polymerized and then reacted with Ac4Glc-SH. The obtained glycopolymers exhibited lower critical solution temperature behavior that could be tuned easily by manipulating the alkyl linker length. Moreover, the binding results obtained both turbidimetry and surface plasmon resonance techniques suggested that the relationship of linker to polymer backbone has a critical influence on glycopolymer-lectin binding behaviour.

Single-Chain Glycopolymer Folding via Host–Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding

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.