Elusive π-helical peptide foldamers spotted by chiroptical studies
| Autor: | Marcin Górecki, Magda Monari, Gennaro Pescitelli, Demetra Giuri, Fabio Bologna, Nicola Castellucci, Gaetano Angelici, Sergio Di Silvio, Matteo Calvaresi, Nicola Zanna, Claudia Tomasini, Lorenzo Milli |
|---|---|
| Přispěvatelé: | Di Silvio S., Bologna F., Milli L., Giuri D., Zanna N., Castellucci N., Monari M., Calvaresi M., Gorecki M., Angelici G., Tomasini C., Pescitelli G. |
| Rok vydání: | 2020 |
| Předmět: |
Diffraction
Chemistry Hydrogen bond Circular Dichroism Organic Chemistry Energy landscape Molecular Dynamics Simulation Vibration Biochemistry Oligomer Protein Structure Secondary Spectral line chemistry.chemical_compound Crystallography Molecular dynamics Thermodynamic Peptide Spectroscopy Fourier Transform Infrared Thermodynamics Pyroglutamic acid Physical and Theoretical Chemistry Peptides Helical peptide |
| Zdroj: | Organic & Biomolecular Chemistry. 18:865-877 |
| ISSN: | 1477-0539 1477-0520 |
| DOI: | 10.1039/c9ob02313e |
| Popis: | A series of oligomers containing alternate l-Ala and pGlu (pyroglutamic acid) both in the L and D form have been prepared and conformationally investigated by X-ray, NMR, UV/ECD, IR/VCD and molecular modelling. X-ray diffraction analysis was possible for the shortest oligomers LL-1 and LD-1. Molecular dynamics simulations of the oligomers demonstrated that the energy landscapes of the LL-series are broad. In contrast, the energy landscapes of the LD-series are characterized by well-defined minima corresponding to specific conformational structures. A single well-defined minimum exists in the energy landscape of the largest oligomer LD-8, corresponding to a precise conformation, characterized by i + 5 → i N-H⋯OC hydrogen bonds, typical of a π-helix. ECD and VCD spectra were measured to identify the chiroptical profiles of the oligomers. The most striking element in the ECD spectra of the LD-series is their exceptionally strong intensity, which confirms that these polypeptides attain a high degree of helical order. VCD spectra for the LD-series are well reproduced by frequency calculations when π-helix folds are employed as input structures, suggesting that a symmetrical VCD couplet around 1720 cm-1 can be taken as the VCD signature of π-helices. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|