Amide Stacking Rivals H-Bonds

Attractive interactions between adjacent amide groups on a peptide backbone can stabilize the molecules in stacked amide conformations, according to a study led by researchers at Purdue University (J. Am. Chem. Soc. 2009, 131, 14243). This type of non-hydrogen-bond interaction between amide groups, which until now has not been studied in detail, is energetically competitive with intramolecular hydrogen bonding—a well-studied process at the center of the coiling and folding arrangements that gives rise to protein secondary structure. William H. James III, Christian W. Müller, Timothy S. Zwier, and coworkers used molecular beam spectroscopy methods coupled with theoretical analysis to probe a model compound that features a three-carbon spacer between two amide groups. The team reports a spectroscopic signature that indicates the compound folds to adopt a conformation in which the two planar amide groups align face-to-face in an antiparallel stacked geometry. “Amide stacking can be used as a design element for conformational control, a strategy that could lead to unique secondary structures not yet anticipated,” the researchers write.