Structural versatility of peptides from C^α,α‐dialkylated glycines. I. A conformational energy computation and x‐ray diffraction study of homo‐peptides from C^α,α‐diethylglycine

Abstract

Abstract Conformational energy computations on a derivative and a homo‐dipeptide of C α,α ‐diethylglycine were performed. In both cases the N‐ and C‐terminal groups are blocked as acetamido and methylamido moieties, respectively. It was found that the C α,α ‐diethylglycine residues are conformationally restricted and that the minimum energy conformation corresponds to the fully extended C 5 structure when the NC α C′ bond angle is smaller than 108° (as experimentally observed). The results of the theoretical analysis are in agreement with the crystal‐state structural propensity of the complete series of N ‐trifluoroacetylated homo‐peptides of this C α,α ‐dialkylated residue from monomer to pentamer, determined by x‐ray diffraction and also described in this work. Interestingly, for the first time, a crystallographically planar peptide backbone was observed (in the protected tripeptide). A comparison with peptides of C α,α ‐dimethylglycine, C α ‐methyl, C α ‐ethylglycine, and C α,α ‐di‐ n ‐propylglycine indicates that the fully extended conformation becomes more stable than the helical structures when both amino acid side‐chain C β atoms are substituted.