Structural versatility of peptides containing Cα,α-dialkylated glycines. An X-ray diffraction study of six 1-aminocyclopropane-1-carboxylic acid rich peptides

The molecular and crystal structures of six fully blocked, Ac3c-rich peptides to the tetramer level were determined by X-ray diffraction. The peptides are Fmoc-(Ac3c)2-OMe·CH3OH, Ac-(Ac3c)2-OMe, , pBrBz-(Ac3c)3-OMe·H2O, Z-Gly-Ac3c-Gly-OTmb·(CH32CO, andt-Boc-(Ac3c)4-OMe·2H2O. Type-I (I′) β-bends and distorted 310-helices were found to be typical of the tri- and tetrapeptides, respectively. In the dipeptides, too short to form β-bend conformations, other less common structural features may be observed. The average geometry of the cyclopropyl moiety of the Ac3c residue is asymmetric and the N-Cα-C′ bond angle is significantly expanded from the regular tetrahedral value. A comparison with the structural preferences of other extensively investigated Cα,α-dialkylated α-amino acids is made and the implications for the use of the Ac3c residue in conformational design are examined.