Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 3 10 helical conformations in which enantiomeric left-and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a righthanded screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.

Low molecular weight gelators that are not easily degraded by enzymes have a range of potential applications. Here, we report new Fmoc-protected dipeptides in which the amide carbonyl group has been replaced by an oxetane ring. Remarkably one of these peptidomimetics, but not the corresponding dipeptide, is an effective gelator, forming hydrogels at a concentration of 3 mg mL. On assembly, there is a lack of beta-sheet structure, implying that there is no requirement for this motif in such a gel. Furthermore, the modified dipeptide is also stable to proteolysis compared to the parent dipeptide.

Solid-phase peptide synthesis (SPPS) is used to create peptidomimetics in which one of the backbone amide C=O bonds is replaced by a four-membered oxetane ring. The oxetane containing dipeptide building blocks are made in three steps in solution, then integrated into peptide chains by conventional Fmoc SPPS. This methodology is used to make a range of peptides in high purity including backbone modified derivatives of the nonapeptide bradykinin and Met-and Leu-enkephalin.Despite resurgent interest in the use of peptides as drugs, 1 their development is often hampered by their poor oral bioavailability and short plasma half-lives. As a consequence, there is intense interest in the discovery of molecules that can mimic the structure and biological function of native peptides yet possess better drug-like properties.

The synthesis and use of oxetane modified dipeptide building blocks in solution and solid-phase peptide synthesis (SPPS) is reported.