Solid phase and combinatorial synthesis of receptors for small peptides
This thesis entails the synthesis and investigations of the properties of novel receptors for small peptides. In chapter I recent developments in host-guest chemistry are reviewed, with particular reference to receptors for carboxylic acids and small peptides. The application of solid phase and combinatorial chemistry to the synthesis of receptors is also described. Chapter II describes the synthesis of a combinatorial library of diamidopyridine derived tweezer receptors with peptidic side-arms. The library was screened with different labelled peptide guests. Screening experiments with dye-labelled tripeptide L-Glu-L-Ser-L-Val-OH showed excellent selectivity and led to the identification of a tweezer receptor structure which was shown to bind the tripeptide with good selectivity over related tripeptide sequences. The results are discussed in relation to previous screening experiments, using the same tripeptide guests, with related tweezer receptor libraries.
Chapter III describes the development of enantioselective receptors for separation of racemic mixtures carried out within an European Network (Milan, Bristol, Madrid).
Synthesis, conformational studies and binding properties of novel 2,6-diamidopyridine derived receptors bearing sulfonamidopeptide side-arms are described. The synthesis and binding properties of guanidinium based receptors for (S)-Naproxen are also described.
Chapter IV describes preliminary investigations towards dynamic combinatorial libraries of guanidinium and 2,6-diamidopyridine based tweezer receptors. The interest focused on dynamic combinatorial systems based on catalysed alkene metathesis and imine formation for selective binding of C-terminal peptides. Although promising results were obtained further investigations are required.