Glycopolymers

Polymers with saccharide groups pendant to the main chain are known as glycopolymers. Due to the specificity of interaction between sugars and cell surface receptor proteins (lectins), glycopolymers are potentially useful materials for applications such as targeted drug delivery, biosensors and protein purification. Glycopolymers can be synthesised either from monomeric glycosides or by functionalisation of a suitably reactive precursor polymer. In our group we favour the former route as it gives more well-defined materials. We have prepared a range of sugar-bearing monomers, including acrylates, methacrylates and methacrylamides. These can be converted to polymers by radical polymerisation, via two conceptually different routes starting from protected sugar equivalents. The protected monomers can be polymerised, then the protecting groups removed; alternatively, the monomers can be deprotected then polymerised. We have found in all cases that the latter route leads to much better defined materials, as evidenced by NMR spectroscopy and elemental analysis.

Surprisingly it has been found that homoglycopolymers often display aggregation behaviour in aqueous solution, forming particles in the size range 50-500 nm. We believe that these are loose aggregates rather than true micelles, due to the lack of an ability to solubilise pyrene. Again, only materials prepared from deprotected monomers give well-defined aggregation behaviour. The interaction of a homopolymer of a beta-D-galactose bearing monomer with the lectinArachis Hypogaea (Peanut Agglutinin, PNA) was studied by isothermal microcalorimetry (ITC) in collaboration with Dr Snjezana Stolnik of the School of Pharmacy at the University of Nottingham. It was found that the glycopolymer had a binding constant around 50 times greater than the free sugar and 10 times greater than the parent monomer. In addition, the binding was found to be entropic in nature, suggesting that the release of surface bound water from the protein is the driving force for binding.

In a related project, we have been developing glycopolymers as vehicles for the delivery of metabolites to mammalian spermatozoa. Water-soluble polymers bearing beta-D-galactose side groups and species such as alpha-tocopherol (vitamin E) have been prepared and incubated with boar spermatozoa for periods up to 10 days. It has been found that the level of vitamin E within the cells increases up to 20 times that found in the control sample. The treated cells also have a much greater resistance to oxidative damage, as evidenced by a much reduced intracellular concentration of malondialdehyde (a marker of lipid peroxidation) following TBARS assay. It has also been found that the viability of treated cells is maintained for longer than untreated cells. This is one of only a handful of successful glycopolymeric delivery systems for bioactive molecules.