A molecular hydrodynamic study of marine based non-digestible fibre polysaccharides considered for use in health products

Marine polysaccharides have been widely used as a source of nutritional supplement for various therapeutic applications. Uncertainties and significant gaps in our knowledge about the macromolecular properties of these substances have limited their use particularly in the pharmaceutical industries where a detailed understanding of materials used for therapies are essential. Therefore, in order to increase our awareness so as to develop better healthcare and therapies against common diseases it is important to establish a better understanding of molecular properties and interactions. The focus of this thesis has been on carrageenans – materials which have arguably been the greatest source of controversy and disagreement in the past in terms of properties – chitosan and alginate and their relations with other substances (mucins, DNA and other polysaccharides). Firstly the main classes of carrageenan - lambda, kappa and iota - have been characterised in terms of their conformation, size and structural integrity utilizing a variety of hydrodynamic techniques including analytical ultracentrifugation based on sedimentation velocity and equilibrium, size exclusion chromatography coupled to multi angle light scattering (SEC-MALS) and viscometry. Studies have suggested that these marine polysaccharides adopt in general semi-flexible structures in solution in contrast to, for example, mucin glycoproteins which adopt a linear random coil conformation. Such conformation analyses are significant in relation to macromolecular structure–function relationships. In addition, the effect of a wide range of solvent conditions was investigated to provide any evidence of dimerization/double helix formation for the main classes of carrageenan (kappa, iota and lambda) using the principal tools of hydrodynamics supported by micro-differential scanning calorimetry. The study showed that, kappa carrageenan adopted a dimeric form under appropriate experimental conditions whereas iota and lambda carrageenan did not. Then, chitosans of different degrees of acetylation were studied, and these too adopted a semi-flexible conformation, but, as with iota and lambda carrageenan, with no evidence of self-association behaviour. A selected group of interactions involving marine polysaccharides or mucin were then investigated. Strong evidence is provided for a clear interaction was observed between chitosan and two polyanions (DNA and xanthan) using the principle of co-sedimentation, and the relevance of this for DNA condensation phenomena is indicated. The use of lambda carrageenan as a possible replacement for alginate in ternary complexes with konjac glucomannan and xanthan for use in the anti-obesity product PolyGlycopleX®, revealed no improvement compared with the use of alginate. Finally, the interaction between the mucin and PolyGlycopleX® was investigated showing that mucin appeared to reinforce interactions between the components of PolyGlycopleX® at higher ionic strengths than seen previously