Cyclopropane analogue of valine: Influence of side chain orientation on peptide folding

The cyclopropane analogue of valine (1-amino-2,2-dimethylcyclopropanecarboxylic acid, c3Val) has been synthesised and incorporated into the model peptides tBuCO-l-Pro-l-c3Val-NHiPr and tBuCO-l-Pro-d-c3Val-NHiPr. In the solid state, both dipeptides accommodate a type II β-turn stabilised by an NHiPr to tBuCO hydrogen bond. Remarkably, the peptide incorporating l-c3Val also exhibits a distorted γ-turn around the cyclopropane residue, with Pro-CO and NHiPr intramolecularly hydrogen-bonded. In the crystalline state, both compounds accommodate a βII-turn conformation. In the dipeptide incorporating l-c3Val, an additional γ-turn centred at the c3Val residue is present.The authors thank the Centro de Excelencia Bruker-ICMA for collection and preliminary treatment of the X-ray diffraction data. Financial support from FEDER and Ministerio de Ciencia y Tecnologı́a (projects PPQ2001-1834 and PPQ2002-819; Ramón y Cajal contract for A.I.J.) is gratefully acknowledged.Peer reviewe