Synergistic n → π* and nN → π*Ar interactions in C-terminal modified prolines: effect on Xaa-Pro cis/trans equilibrium

Carbonyl-carbonyl (COMIDLINE HORIZONTAL ELLIPSISCO) n -> pi* interaction often coexists with a hydrogen bond (HB) or another n -> pi* interaction. Although the interplay between HB and n -> pi* interaction was previously studied, there is no systematic investigation that shows a synergistic relationship of n -> pi* with another noncovalent interaction. Herein, we have studied a set of proline-diacylhydrazine (Pro-DAH) molecules and observed that increase in the strength of the n(N) -> pi*(Ar) interaction on their DAH side strengthened the n -> pi* interaction on the Pro side, which was experimentally determined by measuring the K-trans/cis of the Xaa-Pro amide bond. Overall, we describe a simple C-terminal modification strategy to stabilize the trans-Pro geometry that could be useful to stabilize PPII helices and collagen triple helices that require Pro to adopt the trans amide geometry.

Automated summary

Carbonyl-carbonyl (COMIDLINE HORIZONTAL ELLIPSISCO) n -> pi* interaction often coexists with a hydrogen bond or another n -> pi* interaction. In this study, a set of proline-diacylhydrazine molecules were investigated, and it was found that the increase in the strength of the n(N) -> pi*(Ar) interaction on the DAH side strengthened the n -> pi* interaction on the Pro side. This research provides a simple C-terminal modification strategy to stabilize the trans-Pro geometry, which is important for stabilizing PPII helices and collagen triple helices.