The structure and conformation of saccharides determined by experiment and simulation

1. Introduction

Carbohydrates are the most abundant of all natural products. They show great structural variation which is reflected in a wide range of biological functions.1-4 Their role as structural material and in metabolism has long been recognised. Much of current research is, however, directed towards cell surface saccharides which are of importance for cell recognition and immunology. Capsular polysaccharides (CPS) and lipopolysaccharides (LPS), which surround some bacteria, 5 are often immunogenic and antibodies against these are used for diagnostics. Oligosaccharides on the surface of mammalian cells are involved in cell differentiation and recognition and may also serve as attachment sites for bacteria. 6 The presence of unusual oligosaccharides is often associated with tumours.7 Polysaccharides used in medicine include, e.g. dextran as a plasma substitute, hyaluronic acid in eye-surgery and heparin to prevent blood clotting.
To understand the mechanisms of the various biological interactions of carbohydrates knowledge of both the primary and the secondary structure (conformation) is required. The first part of this thesis discusses the structural analysis of regular polysaccharides using results from component and linkage analysis together with NMR chemical shifts and the computer program CASPER for sequence determination. In the second part the conformational analysis of two monosaccharides with flexible side chains is performed using experimental (NMR-spectroscopy) and computational (molecular modeling) methods.