Effect of Arm Number and Length of Star-Shaped Glycopolymers on Binding to Dendritic and Langerhans Cell Lectins

Abstract

Many cell types in Nature are covered by glycans with a sugar shell on their surface. Synthetic glycopolymer-based materials can mimic these glycans in terms of their variety of biological processes, such as cell growth regulation, adhesion, inflammation by bacteria and viruses, and immune responses. However, the complexity of glycans is still very challenging to be mimicked completely to obtain specific and selective binding ability. Therefore, in this study we aimed to understand how the complexity in the sense of the effect of number of arms and lengths in star-shaped glycopolymers affect the binding activity with different lectins. The Cu-mediated reversible deactivation radical polymerization (Cu-RDRP) technique was employed for the synthesis of mannose containing star-shaped glycopolymers with varying arm number and length. Two sets of star-shaped glycopolymers with on average 1, 3, 7, 8, and 15 arms were successfully synthesized and characterized via 1H NMR, GPC, and DLS. The first set of glycopolymers (Set S1) encompasses 5 star-shaped glycopolymers with a different amount of arms per macromolecule but with equal arm length, whereas in the second set of 5 glycopolymers (Set S2), the amount of sugars per macromolecule was kept constant to obtain glycopolymers with similar glycovalency but in different configuration. Both glycopolymer sets were subsequently evaluated for their lectin-binding affinity toward a series of both newly and previously studied C-type mannose specific lectins present on dendritic and Langerhans cells. Briefly, while Set S1 glycopolymers with the same arm length and different molecular weight showed considerably different biological activities, Set S2 glycopolymers with different arm lengths and the same molecular weight displayed very similar binding abilities, which can indicate that multivalency can be more important than structure complexity to improve the binding behavior of glycopolymers.

Toward Glycomaterials with Selectivity as Well as Affinity

“… 78 Star branched polymannosides varying in only the number and length of arms showed differential responses to immobilized human lectins using SPR. 79 These examples highlight how both precision and, more generally, macromolecular engineering could be easily exploited in the search for selectivity.…”

Tailor-made glycopolymersviareversible deactivation radical polymerization: design, properties and applications

“…1 The cell surfaces are coated with a variety of oligosaccharides, glycosylated proteins, and lipids, typically known as a glycocalyx, which modulate the interaction between cells and different organisms. 2–5 The multivalent interaction between cell-surface glycans and carbohydrate receptors augurs the bio-recognition events essential for various biological processes including signal transmission, intercellular recognition, immune function, fertilization, and pathogen recognition. 5–7 With the advancement of science and technology, the isolation and characterization of glycans from biological sources are currently in progress.…”

“…2–5 The multivalent interaction between cell-surface glycans and carbohydrate receptors augurs the bio-recognition events essential for various biological processes including signal transmission, intercellular recognition, immune function, fertilization, and pathogen recognition. 5–7 With the advancement of science and technology, the isolation and characterization of glycans from biological sources are currently in progress. However, it is still a challenge to explicate the underlying mechanisms involved in the recognition and function of the glycans.…”

“…20–22 Therefore, it is crucial to manipulate the sugar density, length, and architecture of glycopolymers to control the binding rates. 5,20,23,24…”

“…32 In order to acquire precise control over the molecular weight, structural diversity, variable chain length, and epitope density, the use of RDRP methods becomes inevitable. 5,29,33 Atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization, nitroxide-mediated polymerization (NMP), and single electron transfer-living radical polymerization (SET-LRP) are extensively used for the fabrication of well-defined glycopolymers. In addition to the RDRP methods, various post-polymerization and “click” chemistry methods offer further benefits.…”