The folding of a polypeptide chain into the stable threedimensional structure of a biologically active protein is still not understood in atomic detail. However, several research groups have recently reported successful atomistic simulations of secondary-structure formation, including the formation of helices of different types, b turns and b sheets of aand b-peptides. Insight into the nature of both the folding process and the unfolded state 26,27] has been obtained from various studies simulating the reversible folding of peptides. This development is encouraging and indicates that the biomolecular force fields in use are approaching the accuracy required to predict folding equilibria, although this has so far been demonstrated only for short polypeptides. Experimentally, significant progress has been made in the design and synthesis of peptide analogues that mimic secondary-structure elements of proteins, such as a helices, turns, and b sheets. For example, carbopeptoids, homooligomers of sugar-containing amino acids, have been prepared with both furanose and pyranose residues. These carbopeptoids are members of the family of d-peptides which may formally be constructed from a-peptides by replacement of every second peptide fragment with a substituted tetrahydrofuran (THF) or tetrahydropyran ring. These molecules have potential applications as drugs that block protein–protein interactions and inhibit enzyme catalysis. Structural preferences have been investigated in nuclear magnetic resonance (NMR) experiments. Various oligomers with cis configurations at the C2 and C5 atoms of the THF ring (Scheme 1) tend to form conformations reminiscent of a conventional b turn. The characteristic NH(i) O(i 2) hydrogen-bonding pattern has been observed for tetramer 1 in both chloroform and dimethylsulfoxide (DMSO). Chain extension to six or eight residues does not alter the preferred secondary structure. Apparently, hexamer 2 and octamer 3 show the hydrogen-bonding pattern of tetramer 1, extended to six and eight residues, respectively. The trans-linked tetramers appear to have no conformational