Conformational study of an Aib-rich peptide in DMSO by NMR

• Published in: The journal of peptide research Vol. 57; no. 2; pp. 97 - 106
• Main Authors: Bellanda, M., Peggion, E., Mammi, S., Bürgi, R., Van Gunsteren, W.
• Format: Journal Article
• Language: English
• Published: Copenhagen, Denmark Munksgaard International Publishers 01.02.2001
• Subjects: 310-helix; Aib; Dimethyl Sulfoxide - chemistry; DMSO; Hydrogen Bonding; molecular dynamics; NMR; Nuclear Magnetic Resonance, Biomolecular; peptide folding; Peptides - chemistry; Protein Conformation
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.2001.00794.x

: The strong propensity of 2‐amino‐2‐methyl propanoic acid (Aib)‐rich peptides to form stable helical structures is well documented. NMR analysis of the short peptide Z‐(Aib)5‐L‐Leu‐(Aib)2‐OMe indicates the presence of a well‐characterized 310‐helix even in dimethylsulfoxide (DMSO), a solvent known to disrupt helical structures. The structure remains stable at least up to 348 K. Stereospecific assignment of the diastereotopic methyls of Aib was achieved, with the assumption of a specific helical screw sense. The methyl more eclipsed with respect to the CO vector resonates at a higher field in the carbon dimension. Molecular dynamics simulations successfully predict the 3JCHNH coupling constant of Leu6 and most of the H‐bonding pattern. Discrepancies were found for Aib3 and Aib7 amide protons which can be explained by a higher sensitivity of the simulations to the helix fraying at the end of the peptide and by the presence of extended conformations for Leu6 during most of the simulations.