Theoretical and NMR Conformational Studies of β-Proline Oligopeptides With Alternating Chirality of Pyrrolidine Units

Frontiers in Chemistry

Polina M. Ivantcova¹  Vladimir I. Polshakov²  Alexey B. Mantsyzov²  Oleg Y. Savelyev²  Konstantin V. Kudryavtsev⁴  Stefan Bräse⁵ 

[1] Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia;Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia;Institute of Organic Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany;Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russia;Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany;

关键词: β-peptides;    folding;    NMR spectroscopy;    solution structure;    restrained molecular dynamics;    density functional theory (DFT) calculations;   

DOI  :  10.3389/fchem.2018.00091

来源: DOAJ

【 摘 要 】

Synthetic β-peptides are potential functional mimetics of native α-proteins. A recently developed, novel, synthetic approach provides an effective route to the broad group of β-proline oligomers with alternating patterns of stereogenic centers. Conformation of the pyrrolidine ring, Z/E isomerism of β-peptide bonds, and hindered rotation of the neighboring monomers determine the spatial structure of this group of β-proline oligopeptides. Preferences in their structural organization and corresponding thermodynamic properties are determined by NMR spectroscopy, restrained molecular dynamics and quantum mechanics. The studied β-proline oligopeptides exist in dimethyl sulfoxide solution in a limited number of conformers, with compatible energy of formation and different spatial organization. In the β-proline tetrapeptide with alternating chirality of composing pyrrolidine units, one of three peptide bonds may exist in an E configuration. For the alternating β-proline pentapeptide, the presence of an E configuration for at least of one β-peptide bond is mandatory. In this case, three peptide bonds synchronously change their configurations. Larger polypeptides may only exist in the presence of several E configurations of β-peptide bonds forming a wave-like extended structure.

【 授权许可】

Unknown