Hydrogen Bond Surrogate‐Constrained Dynamic Antiparallel β‐Sheets

Antiparallel β‐sheets are important secondary structures within proteins that equilibrate with random‐coil states; however, little is known about the exact dynamics of this process. Here, the first dynamic β‐sheet models that mimic this equilibrium have been designed by using an H‐bond surrogate that introduces constraint and torque into a tertiary amide bond. 2D NMR data sufficiently reveal the structure, kinetics, and thermodynamics of the folding process, thereby leading the way to similar analysis in isolated biologically relevant β‐sheets. Synthetic sheets: The dynamism of short strands between random‐coil and antiparallel β‐sheet states is mimicked in H‐bond‐surrogate (HBS) constrained peptidomimetic models. 2D NMR data yield complete structural, kinetic and thermodynamic details of the β‐sheet⇄non‐β‐sheet equilibrium in these dynamic templates.