Peptide Helices as Rigid Molecular Rulers: A Conformational Study of Isotactic Homopeptides from α‐Methyl‐α‐isopropylglycine, [L‐(αMe)Val]_n

Abstract

Abstract Terminally blocked, isotactic homopeptides from the sterically demanding α‐methylvaline of general formula Y‐[L‐(αMe)Val] n ‐O t Bu (Y = Z, p BrBz, Ac; n = 2–8) have been prepared step‐by‐step in solution and fully characterized. The conformations preferred in solution (β‐turn and right‐handed 3 10 ‐helix) have been assessed by FT‐IR, 1 H NMR and CD spectroscopy. The molecular and crystal structures of the Z‐protected trimer, hexamer, heptamer and octamer have been determined by X‐ray diffraction. In the crystal state, while the trimer is folded in a type III β‐turn conformation, the longest homopeptides form well‐developed, regular, right‐handed 3 10 ‐helices. The screw sense in the helix of the p BrBz‐blocked octamer has been confirmed to be right‐handed by solid‐state and solution CD spectroscopy. The possible exploitation of these peptide helices as rigid and precise molecular rulers is discussed.