Conformational investigation of peptides using solid‐state NMR spectroscopy—A study of polymorphism of β‐turn peptides containing diprolines

Abstract

The construction of complex protein folds relies on the precise conversion of a linear polypeptide chain into a compact 3‐dimensional structure. In this context, study of isolated secondary structural modules containing short stretches of amino acids assumes significance. Additionally, peptides, both natural and synthetic, play a major role as potential drugs. With a view to understand the local conformations adopted by peptides in the solid state, we propose a multinuclear NMR approach utilizing spectra of nuclei in their natural isotopic abundance. Various solid‐state NMR experiments have been utilized for assignment of the spectra. Additionally, the gauge‐including projector augmented‐wave (GIPAW) calculations were used to confirm the assignments. Particularly, the utility of the double‐quantum–single‐quantum correlation experiments is highlighted for the purpose of assignment and for inferring the conformation across the peptide bond. The methodology is illustrated for the case of designed peptides containing diproline residues occurring at the β‐turns for identifying their cis‐trans conformational polymorphism. The proposed method promises to be of use in the study of conformations of small‐ to medium‐sized peptides such as antimicrobial peptides and in the study of polymorphism leading to applications in drug development protocols.

Monitoring the Site-Specific Solid-State NMR Data in Oligopeptides

“…In particular, the eigenvector associated with the least shielded eigenvalue is significantly (by more than 20°) tilted off the peptide plane (see Figure 6). This information could be useful in future studies of prolyl-containing peptides [39].…”

“…In particular, the eigenvector associated with the least shielded eigenvalue is significantly (by more than 20 • ) tilted off the peptide plane (see Figure 6). This information could be useful in future studies of prolyl-containing peptides [39]. nonproteinogenic amino acids (see Table 4), and hydroxyproline sites feature a specific orientation of their 15 Namid CST.…”

Synergy of Solid-State NMR, Single-Crystal X-ray Diffraction, and Crystal Structure Prediction Methods: A Case Study of Teriflunomide (TFM)

“…Solid-state NMR spectroscopy is very sensitive to local molecular disorder (including dynamic disorder) and structural defects. Thus, it is no surprise that this method is frequently used in different branches of science, in particular in the pharmaceutical sciences, to study structural features and to verify the quality and/or homogeneity of the studied material. − …”