Intramolecular H-bonds and thioamide rotational isomerism in thiopeptides.
Mono- and dithionated N-acyl amino acid and dipeptide N'-methylamides were synthesized using Lawesson's reagent and S-thioacetyl thioglycolic acid. The conformation of the thionated models was characterized by IR, 13C, and 1H NMR spectroscopy, including NOE experiments. The formation of -C = S...H-N-C = X (X = O or S) intramolecular H-bonds of the type 2----2, 1----3 and 1----4 was evidenced by the characteristic shifts of the IR stretching frequencies of the NH group. Act-Pro-NHCH3(4) and Act-Prot-NHCH3(5) were found to be present as mixtures of rotational isomers about the CS-N bond. 13C chemical shifts of the gamma- and beta-carbons of the proline ring elucidated the conformation (Z or E) of the tertiary thioamide group. Our results suggest that the conformation of thiopeptides is determined by two factors: 1) the H-bond donating and accepting ability of the thioamide group and 2) the repulsion between the thiocarbonyl sulfur atom and the side chain groups of the neighbouring amino acid residues.
Hollósi
M
M
Institute of Organic Chemistry, L. Eötvös University, Budapest, Hungary.
Zewdu
M
M
Kollát
E
E
Majer
Z
Z
Kajtár
M
M
Batta
G
G
Kövér
K
K
Sándor
P
P
D004151:Dipeptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D013854:Thioamides / Q000737:chemistry*
D004151:Dipeptides; D013854:Thioamides