Nh2

Figure 30

Gellman introduced the term "foldamer'' to refer to "any polymer with strong tendency to adopt a specific compact conformation'' [57]. Early work from his group exemplified the rational design process. Computer-assisted analysis of several amido-linked ¡-amino acids led to the proposal that trans 2-amino hexanoic acid and trans 2-amino pentanoic acid would form stable helical structures. Modeling predicted that the hexanoic system would form a 14-helix and the pentanoic system a 12-helix (Fig. 32). These structures were synthesized and their conformations were experimentally verified using a combination of NH/ND exchange rates, circular dichroism (CD), and X-ray crystallography.

Seebach et al. reported the synthesis of ¡- and y-peptides with stable secondary structures [58] and, independently, Hanessian et al. reported the synthesis of y-pep-tides that adopt helical structures in solution [59]. These combined studies showed important structural characteristics for ¡- and y-peptides in contrast with a-peptides. For example, a-peptides adopt helical conformations stabilized by a 13-membered hydrogen bond between the carbonyl of the amino terminus and the amide NH of the fourth residue toward the C-terminus (3.6 residues per turn). ¡-Peptides formed

BnO BnO-

dimer

0 0

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