A new enzymatic approach for the synthesis of oligosaccharides.
Oligosaccharides are known to be notoriously difficult to synthesise in high yields and good purity. As a consequence, our understanding of their properties and functions lags behind our understanding of the other biopolymers, proteins and nucleic acids. This thesis presents phosphorylase-mediated dynamic combinatorial chemistry as a new approach for the synthesis of oligosaccharides. The use of enzymes, such as phosphorylase, to generate dynamic and adaptive systems is intriguing compared to the use of traditional organic reactions, as enzymes can catalyse the formation of biopolymers with high regio- and stereoselectivity
Phosphorylase can elongate and shorten linear α 1,4 glucans in a reversible manner, thus forming a dynamic mixture of different length oligosaccharides. In this thesis, a carefully chosen template was added to the mixture, and thereby the equilibrium shifted towards the α 1,4 glucan that bound most strongly to the template. The template, consisting of two hydrophilic groups linked together with an aliphatic chain, was chosen based on the ability of linear α 1,4 glucans to form helices around hydrophobic guests.
This thesis also presents new insight into the solution structure and recognition properties of α 1,4 glucans obtained through NMR experiments and molecular modelling simulations. It was found that the α 1,4 glucans indeed form a left-handed helix around the template, but also that linear α 1,4 glucans above a certain minimum length can dimerise in aqueous solution. Our belief is that α 1,4 glucans with their unique ability to act as flexible hosts for hydrophobic guests in water, have potential for various applications including drug delivery and molecular transport.
