عنوان

Synthesis of glycomaterials for multivalent interactions

TLets714964

Synthesis of glycomaterials for multivalent interactions

[Thesis]

Yilmaz, Gokhan

University of Warwick

2016

Thesis (Ph.D.)

2016

Carbohydrates have attracted much attention to insert their biological properties into nanostructured materials due to their use for bio-mimetic purposes, their crucial role in bio-recognition processes at molecular level and their functional role in living systems. Glycopolymers, which are synthetic macromolecules with sugar moieties, exhibit a crucial role for many biological processes such as signal transmission, intercellular recognition and fertilization. The interaction between carbohydrates and lectins could be greatly enhanced by the multivalent effect of densely packed carbohydrate molecules with unique functionalities, which is known as the "glycocluster effect". Therefore, the investigation of this specific interaction between glycopolymer and protein is very important to create more complex and biologically relevant carbohydrate mimics. Well-defined amphiphilic block glycopolymers with the same mannose content have been self-assembled in aqueous solution to form glyconanoparticles with different morphologies (spherical, worm-like micelles and vesicles). The size and shape of nanoparticles have significant effects on the binding affinities with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DCSIGN). Moreover, the obtained glyco-micelles have a great potential for drug delivery applications. Glycopolymer-coated gold nanoparticles (glyco-AuNPs) which were synthesized with reversible addition-fragmentation chain transfer (RAFT) polymerization were combined with doxorubicin (DOX) as a model anticancer drug by creating a pHsensitive hydrazone linkage in the presence of cysteine (Cys) and a cross-linker for both chemotherapy and radiation therapy. The reversible single-chain glycopolymer folding structures in α-shape with different sugar moieties were created to investigate the influence of this folded collapse on the binding capability with different lectins. The single-chain folding structures were achieved by the host-quest interaction of β-cyclodextrin and adamantane in very high diluted aqueous solution. The binding results evidenced that these single-chain folded structures enhanced greatly the multivalent interaction. A new S-glucosyl substituted 2-oxazoline glycomonomer was synthesized via thiolene "click" chemistry and then polymerized using cationic ring-opening polymerization (CROP) technique. In order to investigate the effect of S-glucosyl substituent linker length on the cloud point and binding ability systematically, A series of well-defined glyco-copolymers with different sugar linker length to the polymer backbone was prepared. The obtained results showed that it has a significant influence on the cloud point and binding capability.

QD Chemistry

Yilmaz, Gokhan

University of Warwick

p

[Thesis]

276903

a

Y