Synthesis and Structure of α/δ-Hybrid Peptides—Access to Novel Helix Patterns in Foldamers

Stimulated by an overview on all periodic folding patterns of a/d- hybrid peptides with 1:1 alternating backbone provided by ab initio molec- ular orbital theory, the first representa- tives of this foldamer class were syn- thesized connecting novel C-linked carbo-d-amino acid constituents and l- Ala. In agreement with theoretical pre- dictions, extensive NMR spectroscopic analyses confirm the formation of new motifs of 13/11-mixed helical patterns in these peptides supported by the ri- gidity of the d-xylose side chain in the selected d-amino acid constituents. Re- lationships between possible helix types in a/d-hybrid peptides and their counterparts in other 1:1 hybrid pep- tide classes and native a-peptides are discussed; these indicate the high po- tential of these foldamers to mimic native peptide secondary structures. The design of a/d-hybrid peptides pro- vides an opportunity to expand the domain of foldamers and allows the in- troduction of desired functionalities through the a-amino acid constituents.