Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker.

Diazocines are characterized by extraordinary photochemical properties rendering them of particular interest for switching the conformation of biomolecules with visible light. Current developments afford synthetic access to unprecedented diazocine derivatives promising particular opportunities in photocontrol of proteins and biological systems. In this work, the well-established approach of photocontrolling the secondary structure of α-helices was exploited using a diazocine to reversibly fold and unfold the tertiary structure of a small protein. The protein of choice was the globulary folded Trp-cage, a widely used model system for the elucidation of protein folding pathways. A specifically designed, short and rigid dicarboxy-functionalized diazocine-based cross-linker was attached to two solvent-exposed side chains at the α-helix of the miniprotein through the use of a primary amine-selective active ester. This cross-linking strategy is orthogonal to the common cysteine-based chemistry. The cross-linked Trp-cage was successfully photoisomerized and exhibited a strong correlation between protein fold and diazocine isomeric state. As determined by NMR spectroscopy, the cis-isomer stabilized the fold, while the trans-isomer led to complete protein unfolding. The successful switching of the protein fold in principle demonstrates the ability to control protein function, as the activity depends on their structural integrity.

Facile Synthesis of Light-Switchable Polymers with Diazocine Units in the Main Chain.

Unlike azobenzene, the photoisomerization behavior of its ethylene-bridged derivative, diazocine, has hardly been explored in synthetic polymers. In this communication, linear photoresponsive poly(thioether)s containing diazocine moieties in the polymer backbone with different spacer lengths are reported. They were synthesized in thiol-ene polyadditions between a diazocine diacrylate and 1,6-hexanedithiol. The diazocine units could be reversibly photoswitched between the (Z)- and (E)-configurations with light at 405 nm and 525 nm, respectively. Based on the chemical structure of the diazocine diacrylates, the resulting polymer chains differed in their thermal relaxation kinetics and molecular weights (7.4 vs. 43 kDa) but maintained a clearly visible photoswitchability in the solid state. Gel permeation chromatography (GPC) measurements indicated a hydrodynamic size expansion of the individual polymer coils as a result of the Z→E pincer-like diazocine switching motion on a molecular scale. Our work establishes diazocine as an elongating actuator that can be used in macromolecular systems and smart materials.