Structural versatility of peptides from Cα,α-disubstituted glycines. Preferred conformation of the Cα,α-dibenzylglycine residue
Abstract
The preferred conformation of the Cα,α-dibenzylglycine residue has been assessed in selected derivatives and small peptides by conformational energy computations, 1H NMR spectroscopy, and X-ray diffraction. Conformational energy computations on the Cα,α-dibenzylglycine monopeptide, Ac-Dbz-NHMe, strongly support the view that this Cα,α-symmetrically disubstituted residue is conformationally restricted and that its minimum energy conformation falls in the fully-extended (C5) region. The results of the theoretical analysis are in agreement with the solution and crystal-state structural propensity of Tfa-Dbz-Gly-DBH, Tfa-Dbz-L-Phe-OMe and its benzyl ester analogue, m-ClAc-Dbz-OH, Z-Gly-Dbz-Gly-OH and its t-butyl ester derivative. The implications for the use of the Dbz residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.