Amphiphilic glycopolymers and glycopeptides. properties and applications

In this thesis, the properties and potential application fields of saccharide-based
block copolymers are explored.
The anionic polysaccharide heparin was coupled to hydrophobic blocks –
poly(dimethyl siloxane) (PDMS) and poly (ethyl ethylene) (PEE) – using different
synthetic methods, and investigated in terms of self-assembly behavior and insertion
into polymeric membranes. We studied whether heparin’s intrinsic anticoagulant
activity is persistent upon chemical transformation and insertion into polymer
membranes. We observed that coupling does not influence the anticoagulant activity,
whereas methods involving degradation of heparin led to an almost complete loss of
activity. We also coupled heparin to the hydrophilic polymer poly(ehtylene glycol) (PEG),
which produced a bis-hydrophilic block copolymer. Self-assembly of this anionic
material in association with gadolinium cations was investigated by transmission
electron microscopy. Electron paramagnetic resonance (EPR) spectroscopy provided
more details about the polymer – metal interactions. The choice of gadolinium was
justified by the fact that it has good contrast properties for medical imaging. In
combination with the polymer, toxicity of gadolinium could be decreased. In addition,
its relaxivity was enhanced. This way we obtained a new type of contrast agent.
MRI experiments proved that the relaxivity of the polymer-bound gadolinium was
significantly higher than of unbound gadolinium and of commercially available
gadolinium-based contrast agents. To further lower toxicity of gadolinium, we added
phosphate to form small insoluble GdPO4 particles, which were in fact stabilized in
solution by polymer aggregates. Their contrast properties only slightly decreased
compared to polymer-bound gadolinium ions.
Apart from synthetic blocks, we also combined sugar units with peptides. Firstly, we
established new synthetic routes towards such biohybrids, using monosaccharides
and a short peptide (named TRUNK). The coupling of D-glucuronic acid to the
TRUNK was successfully achieved on solid phase. The resulting glycopeptide was
investigated in terms of its self-assembly behavior. This thesis is structured in eight parts. The first chapter is an introduction, focusing on
amphiphiles and copolymers based on biological blocks. Chapter two includes the
motivation and the concept of this work. In the third chapter, the results are described
and discussed in detail. This chapter is divided into four main sections, dealing with
heparin-based copolymers with amphiphilic as well as bis-hydrophilic properties. The
latter was explored as a matrix for MRI contrast agents. Additionally, the synthesis
and self-assembly behavior of materials combining carbohydrate and peptide blocks
are discussed.
In chapters four and five we draw the conclusions and present the outlook for
prospective experiments. The experimental conditions are given in chapter six, as
well as descriptions of methods and equipment. The thesis finalizes with the
references in chapter seven and an appendix including a historical outline of heparin
in chapter eight.