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

The strong propensity of 2-amino-2-methyl propanoic acid (Aib)-rich peptide s 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 wel l-characterized 3(10)-helix even in dimethylsulfoxide (DMSO), a solvent kno wn to disrupt helical structures. The structure remains stable at least up to 348 K. Stereospecific assignment of the diastereotopic methyls of Aib wa s achieved, with the assumption of a specific helical screw sense. The meth yl more eclipsed with respect to the CO vector resonates at a higher field in the carbon dimension. Molecular dynamics simulations successfully predic t the (3)J(CHNH) coupling constant of Leu(6) and most of the H-bonding patt ern. Discrepancies were found for Aib(3) and Aib(7) amide protons which can be explained by a higher sensitivity of the simulations to the helix frayi ng at the end of the peptide and by the presence of extended conformations for Leu6 during most of the simulations.