A Unique and Stable Polyproline I Helix Sorted out from Conformational Equilibrium by Solvent Polarity

Polyproline I helical structures are often considered
as the hidden
face of their most famous geminal sibling, Polyproline II, as PPI
is generally spotted only within a conformational equilibrium. We
designed and synthesized a stable Polyproline I structure exploiting
the striking tendency of (S)-indoline-2-carboxylic
acid to drive the peptide bond conformation toward the cis amide isomer, when dissolved in polar solvents. The cooperative
effect of only four amino acidic units is sufficient to form a preferential
structure in solution. We shed light on this rare secondary structure
with a thorough analysis of the spectroscopic and chiroptical properties
of the tetramer, supported by X-ray crystallography and computational
studies.