The Design and Synthesis of Alanine-Rich α-Helical Peptides Constrained by an S,S-Tetrazine Photochemical Trigger: A Fragment Union Approach

The design and synthesis of alanine-rich α-helical peptides constrained in a partially unfolded state by incorporation of the S,S-tetrazine phototrigger has been achieved, permitting, upon photochemical release, observation by 2D-IR spectroscopy of the subnanosecond conformational dynamics that govern the early steps associated with α-helix formation. Solid-phase peptide synthesis was employed to elaborate the requisite fragments, with full peptide construction via solution-phase fragment condensation. The fragment union tactic was also employed to construct 13C═18O isotopically edited amides to permit direct observation of conformational motion at or near specific peptide bonds.