NXO beta structure mimicry: an ultrashort turn/hairpin mimic that folds in water

Abstract

We report the first application of NXO-pseudopeptides for β-turn mimicry. Incorporating the proline-derived NProO peptidomimetic building block, a minimal tetrapeptide β-hairpin mimic has been designed, synthesized and its solution structure elucidated. Emulating a natural proline–glycine β-turn, evidence from NMR, molecular modeling and CD suggests the formation of two rapidly interconverting hairpin folds in water, methanol and dimethyl-sulfoxide at room temperature, displaying the proline nitrogen amide bond in either cis or trans arrangement. The NProO-modified hairpin features peptidic backbone dihedrals Φ, Ψ characteristic of natural proline-containing turns composed of α-amino acids only. Taken together, the observed folding behavior and inherently high designability render the NProO motif a building block for β-structure elaboration in aqueous medium.