beta-Peptides, i.e. oligomers of beta-amino acids, containing as few as six residues may form surprisingly stable helices, with half-lives for the H/D exchange of the central NH protons of up to several days. Furthermore, these beta-peptides (carrying the side chains of familiar alpha-amino acids such as Ala, Val, Leu, Phe, Lys in the 2- and/or 3-position of their 3-amino carboxylic moieties) have been shown to be stable to common peptidases for at least two days. In this article, a brief account of the results obtained since we started work in this area in early 1995 is given. The synthesis of enantiopure beta-amino acids can be achieved by homologation of alpha-amino acids. The greater structural variability of beta-amino acids leads to an even greater multitude of possible beta-peptide primary and secondary structures. Circular dichroism, NMR and X-ray investigations have unveiled helical, pleated-sheet and tubular arrangements of linear and cyclic beta-peptides composed of up to twelve beta-amino acids. The prospects for the use of beta-peptides as drugs, the construction of large, enzymatically-active beta-proteins and their interaction with the natural, alpha-peptidic counterparts are discussed.
