Étude structurale de la liaison thioamide: Synthèse et conformation de dérivés de la thioalanine et de la thioglycine

Abstract

The present study reports the synthesis, crystal structure determinations, and the conformational analysis of N-tertiobutyloxycarbonyl N′-methylthioalanine (Boc-AlaS-NHCH3, C9H18N2O2S) and of N-tertiobutyloxycarbonyl N′-methylthioglycine (Boc-GlyS-NHCH3, C8H16N2O2S). The particular feature of these compounds is the replacement of the classical oxopeptide linkage by a thioamide bond. Crystals of Boc-AlaS-NHCH3 are tetragonal, space group P43212. Those of Boc-GlyS-NHCH3 are monoclinic, space group P21/c. Both structures were solved by direct methods and refined by full-matrix least-squares methods to Rw = 0.045 and 0.035 for 827 and 1335 reflections respectively, with intensities greater than 2.5σ(I). The conformations of both compounds correspond to conformational energy minima, calculated for classical amino acids. The C=S bond lengths of 1.665(9) and 1.650(3) Å constitute the major difference compared to oxopeptides; the crystal structures reveal that the presence of the sulfur atom does not change the electronic properties of the peptide bond. Using a classical method for the study of peptides (ECEPP/2), conformational energy maps were computed for derivatives of dithioalanine and dithioglycine and are compared to the oxo residues. We conclude that the synthesis and conformational analysis of thionated amino acids allow us to introduce the thioamide linkage into more complex peptide structures and to predict the conformational behaviour. Keywords: molecular conformations, peptidic structure, crystallography.