Stabilization\nof 3<sub>10</sub>-Helices in Macrocycles\nUsing Dominant Rotor Methodology

Stabilization\nof biologically relevant structural motifs has been\na long-standing challenge. Here we show that atropisomeric dominant\nrotors can stabilize rare 3<sub>10</sub>-helices in macrocycles. The\ntarget molecules were prepared using solid-phase peptide synthesis\nand subjected to extensive structural analysis. Molecular dynamics\n(MD) simulations enabled us to acquire solution structures for the\ntarget molecules, which offered evidence for stable 3<sub>10</sub>-helix formation, ordinarily a metastable state. The 3<sub>10</sub>-helices were shown to retain helicity after heating to 100 °C\nfor 72 h. Moreover, the crude atropisomeric mixtures could be thermally\nenriched toward 3<sub>10</sub>-helical macrocycles with selectivities\nof >20:1.