Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues

Abstract

Post-translational modified thiazole-amino acid (Xaa-Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Conformational study of the series of model compounds containing this structural motif with alanine, dehydroalanine, dehydrobutyrine and dehydrophenylalanine were performed using DFT method in various environments. The solid-state crystal structure conformations of thiazole-amino acid residues retrieved from the Cambridge Structural Database were also analysed. The studied structural units tend to adopt the unique semi-extended β2 conformation; which is stabilised mainly by N-H⋯N_Tzl hydrogen bond, and for dehydroamino acids also by π-electron conjugation. The conformational preferences of amino acids with a thiazole ring were compared with oxazole analogues and the role of the sulfur atom in stabilising the conformations of studied peptides was discussed.