WW domains, named after two highly conserved tryptophan residues (W), adopt a compact, triple stranded β-sheet structure. Due to their small size (30-40 amino acids) they are suitable model systems to study β-sheet folding and stability. An essential requirement for the work was the development of an efficient strategy to assemble the WW domain of the formin-binding protein 28 (FBP28 WW) and related mutants via solid phase peptide synthesis, enabling also the integration of non-natural amino acids. The difficult synthesis of these sequences had to be substantially improved which was accomplished when X-Ser/ X-Thr oxazolidine building blocks (pseudo-prolines) were applied. The second part aimed at the impact of amino acid side chain interactions on the stability of the FBP28 WW domain. The synergies of selected amino acid side chains within a set of 5 potentially interacting residues were investigated. The results show that one hydrophobic pair (Tyr21/ Leu26) was particularly important for the stability of the β-sheet. Nevertheless, these residues could be replaced, surprisingly, by more hydrophilic, potentially hydrogen bond forming glutamines. Moreover, the use of non-natural amino acid building blocks together with site-directed 13C1(4)- labelling of distinct tyrosine side chains led to new findings about the nature and impact of the Tyr19 side chain interaction.