Turn and Sheet Structures

Optimal pre-organization of the y-peptide backbone towards the formation of open-chain turn-like motifs is promoted by unlike-y -amino acid residues. This design principle can be rationalized by examination of the two conformers free of syn-pentane interaction (f and II , Fig. 2.34). Tetrapeptide 150 built from homo-chiral unlike-y -amino acid building blocks 128e has been shown by NMR experiments in pyridine to adopt a reverse turn-like structure stabilized by a 14-mem-bered H-bond pseudocycle [202] (Fig. 2.37 A). 

The formation of an intramolecular H-bond is supported by the slower rate of amide proton exchange in pyridine/10% CD3OD. The influence of the stereochemistry on turn formation and turn geometry has been investigated. Seebach and coworkers have demonstrated that dipeptide sequences consisting 

While conformation II (Fig. 2.34) of Uke-y -amino acids is found in the 2.614-helical structure, conformation I, which similarly does not suffer from sy -pen-tane interaction, should be an appropriate alternative for the construction of sheet-like structures. However, sheet-like arrangement have not been reported so far for y-peptides composed of acyclic y -amino acid residues. Nevertheless, other conformational biases (such as a,/9-unsaturation, cyclization between C(a) and C(y)) have been introduced into the y-amino acid backbone to restrict rotation around ethylene bonds and to promote extended conformation with formation of sheets in model peptides. Examples of such short chain y-peptides forming antiparallel (e.g. 152 [208]) and parallel (e.g. 153-155 [205, 208]) sheet-hke structures are shown in Fig. 2.38. 

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