This thesis set out to explore the conformational properties of short designed peptide sequences, in which transitions between structural states may be anticipated. The use of conformationally constrained residues like α-aminoisobutyric acid (Aib) and D-proline (DPro) permits the design of model sequences for structural studies. The principle of imposing conformational constraints by multiple substitutions at backbone atoms in aminoacid residues may also be extended to the higher homologs of α-amino acids, namely β and residues. The experimental results presented in this thesis also examine the potential of using cross-strand interactions between aromatic residues as a probe of structure in designed peptide β-hairpins. Chapter 1 provides a very brief introduction to the necessary background on which the experimental studies in this thesis are based. Chapter 2 describes studies aimed at establishing chain length effects on helix-hairpin conformational distributions in short synthetic sequences, containing centrally positioned Aib-DAla and Aib-Aib segments.The Aib-DAla dipeptide segment has a tendency to form both type-I'/III' and type-I/III β-turns. The occurrence of prime turns facilitates the formation of β-hairpin conformations, while type-I/III turns can nucleate helix formation. The octapeptide Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (1) has been previously shown to form a β-hairpin in the crystalline state and in solution. The effects of sequence truncation have been examined using the model peptides Boc-Phe-Val-Aib-Xxx-Leu-Phe-NHMe (2, 6), Boc-Val-Aib-Xxx-Leu-NHMe (3, 7) and Boc-Aib-Xxx-NHMe (4, 8), where Xxx = DAla, Aib. For peptides with central Aib-Aib segments, Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe (6), Boc-Val-Aib-Aib-Leu-NHMe (7) and Boc-Aib-Aib-NHMe (8) local helical conformations have been established by NMR studies in both hydrogen bonding (CD3OH) and non-hydrogen bonding (CDCl3) solvents. In contrast, the corresponding hexapeptide Boc-Phe-Val-Aib-DAla-Leu-Phe-Val-NHMe (2) favors helical conformations in CDCl3 and β-hairpin conformations in CD3OH. β-Turn conformations (type-I /III) stabilized by intramolecular 4 1 hydrogen bonds are observed for the peptide Boc-Aib-DAla-NHMe (4) and Boc-Aib-Aib-NHMe (8) in crystals. The tetrapeptide Boc-Val-Aib-Aib-Leu-NHMe (7) adopts an incipient 310-helical conformation stabilized by three 4 1 hydrogen bonds. The peptide Boc-Val-Aib-DAla- Leu-NHMe (3) adopts a novel -turn conformation, stabilized by three intramolecular hydrogen bonds (two 4 1 and one 5 1). The Aib-DAla segment adopts a type-I' β-turn conformation. The observation of the NOE Val(1) NH HNCH3 (5), in CD3OH, suggests that the solid state conformation of peptide 3 is maintained in methanol solutions. Peptide hairpins provide an ideal scaffold for exploring cross-strand interactions between residues on facing antiparallel strands. Chapter 3 reports studies directed towards probing, aromatic interactions between facing Phe residues, positioned at the non-hydrogen bonding positions in designed octapeptide β-hairpins. The studies described in this Chapter employ ring current shifted aromatic proton resonances as a means of probing aromatic ring orientations. Crystal structures of eight peptide -hairpins with the sequence Boc-Leu-Phe-Val-Xxx-Yyy-Leu-Phe-Val-OMe revealed that the Phe(2) and Phe(7) aromatic rings are in close spatial proximity, with a centroid-centroid distance (Rcen) of 4.4Å to 5.4Å between the two phenyl rings. Proton NMR spectra in chloroform and methanol solutions reveal a significant upfield shift of the Phe(7) C , ′ H2 protons (6.65 ppm to 7.04 …