mixed helical structures have not yet been observed experimentally in g- and d-peptides synthesized so far.
Another general approach to introduce periodicity at the level of a dimeric unit in oligoamides is to mix two types of o-amino acid residues in an alternating fashion. Such so-called heterogeneous or hybrid peptide backbones show considerable promise to expand the pool of candidate foldamers, and their experimental folding patterns are discussed with greater details in Section 2.6. Employing the methods of ab initio MO theory, Hofmann and co-workers have investigated the ensembles of helical structures attainable with (unsubstituted) a,b-, a,g- and b,g-hybrid backbones [155, 156]. Conformational analysis provided three groups of helical structures according to their global H-bonding pattern: helices with all H bonds in one direction (either forward or backwards direction), and mixed helices. For all three heterogeneous backbones, the most stable conformations at the HF and DFT level of ab initio theory were found among mixed helices (i.e. 18/16-(and 11/9-), 18/20- and 20/22-helical folds for a,b-, a,g- and b,g-peptide hybrids, respectively, see Fig. 2.12). In an aqueous environment (PCM/HF/6-31G* calculations), the stability of helices with unidirectional H-bonding increases at the expense of mixed helices. It is worth mentioning that some mixed helices such as the 11/9-helix of a,b-peptides remain significantly stable. Experimental evidence for the 11/9-helical fold came from NMR studies in CDCl3 of a series of a,b-peptides consisting of l-Ala/(3S)-carbofuranosyl-b3-amino acid repeat (e.g. 22,
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