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

Yarava, Jayasubba Reddy; Nishiyama, Yusuke; Raghothama, Srinivasarao; Ramanathan, K. V.

doi:10.1111/cbdd.13649

Cited by 4 publications

(3 citation statements)

References 58 publications

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“…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].…”

Section: Discussionmentioning

confidence: 97%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Czernek

Brus

2020

IJMS

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Reliable values of the solid-state NMR (SSNMR) parameters together with precise structural data specific for a given amino acid site in an oligopeptide are needed for the proper interpretation of measurements aiming at an understanding of oligopeptides’ function. The periodic density functional theory (DFT)-based computations of geometries and SSNMR chemical shielding tensors (CSTs) of solids are shown to be accurate enough to support the SSNMR investigations of suitably chosen models of oriented samples of oligopeptides. This finding is based on a thorough comparison between the DFT and experimental data for a set of tripeptides with both 13Cα and 15Namid CSTs available from the single-crystal SSNMR measurements and covering the three most common secondary structural elements of polypeptides. Thus, the ground is laid for a quantitative description of local spectral parameters of crystalline oligopeptides, as demonstrated for the backbone 15Namid nuclei of samarosporin I, which is a pentadecapeptide (composed of five classical and ten nonproteinogenic amino acids) featuring a strong antimicrobial activity.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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

Czernek

Brus

2020

IJMS

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“…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. − …”

Section: Introductionmentioning

confidence: 99%

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

Pawlak

Sudgen

Bujacz

et al. 2021

Crystal Growth & Design

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In this work, for the first time, we present the X-ray diffraction crystal structure and spectral properties of a new, room-temperature polymorph of teriflunomide (TFM), CSD code 1969989. As revealed by DSC, the low-temperature TFM polymorph recently reported by Gunnam et al. undergoes a reversible thermal transition at −40 °C. This reversible process is related to a change in Z’ value, from 2 to 1, as observed by variable-temperature 1 H– 13 C cross-polarization (CP) magic-angle spinning (MAS) solid-state NMR, while the crystallographic system is preserved (triclinic). Two-dimensional 13 C– 1 H and 1 H– 1 H double-quantum MAS NMR spectra are consistent with the new room-temperature structure, including comparison with GIPAW (gauge-including projector augmented waves) calculated NMR chemical shifts. A crystal structure prediction procedure found both experimental teriflunomide polymorphs in the energetic global minimum region. Differences between the polymorphs are seen for the torsional angle describing the orientation of the phenyl ring relative to the planarity of the TFM molecule. In the low-temperature structure, there are two torsion angles of 4.5 and 31.9° for the two Z’ = 2 molecules, while in the room-temperature structure, there is disorder that is modeled with ∼50% occupancy between torsion angles of −7.8 and 28.6°. These observations are consistent with a broad energy minimum as revealed by DFT calculations. PISEMA solid-state NMR experiments show a reduction in the C–H dipolar coupling in comparison to the static limit for the aromatic CH moieties of 75% and 51% at 20 and 40 °C, respectively, that is indicative of ring flips at the higher temperature. Our study shows the power of combining experiments, namely DSC, X-ray diffraction, and MAS NMR, with DFT calculations and CSP to probe and understand the solid-state landscape, and in particular the role of dynamics, for pharmaceutical molecules.

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Deciphering the Conformations of Glutathione Oxidized Peptide: A Comparative NMR Study in Solution and Solid‐State Environments

Senapati,

Yarava,

Ramanathan

et al. 2024

Magnetic Reson in Chemistry

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Glutathione (GSH) and its oxidized dimer (GSSG) play an important role in living systems as an antioxidant, balancing the presence of reactive oxygen species (ROS). The central thiol (‐S‐S‐) bond in GSSG can undergo free rotation, providing multiple conformations with respect to the S‐S bridge. The six titratable sites of GSSG, which are influenced by pH variations, affect these conformations in solution, whereas in solids, additionally crystal packing effects come into play. In view of differing reports about the structure of GSSG in literature, we have here conducted an extensive reexamination of its conformations using NMR, and contrasting results have been obtained for solution and solid state. In solution, the existence of more than one antiparallel orientation of the monomer unit with different hydrogen bonding schemes has been indicated by NOE and amide temperature coefficient results. On the other hand, in the solid‐state, a 1H‐1H double‐quantum (DQ) to 13C single‐quantum (SQ) correlation study has confirmed a parallel orientation, consistent with the reported X‐ray crystal structure. Experimentally assigned solid‐state NMR resonances have been validated using GIPAW calculations incorporated in the Quantum ESPRESSO package.

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

Cited by 4 publications

References 58 publications

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

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

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

Deciphering the Conformations of Glutathione Oxidized Peptide: A Comparative NMR Study in Solution and Solid‐State Environments

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