Photopharmacology
Red-shifting azobenzenes
Most photopharmaceuticals developed so far use an azobenzene derivative as the photoswitch. Unmodified azobenzenes require UV light for swicthing, but this can be damaging to cells and has poor tissue penetration. We have made a series of discoveries that have led to the development of azobenzenes that switch with red or even near-IR wavelengths. This allows much superior tissue penetration.
Azo-proteins
When azobenzenes are attached to peptides and proteins the change in azobenzene conformation can be used to induce changes in the structure of the protein. We found that introduction of a thiol-reactive azobenzene-based cross-linker at cysteine (Cys) residues spaced 11 residues apart in an alpha helix can be used to control the stability of the helix. We studied this system in detail and found that the trans form of the cross-linked peptide is helical in water whereas the cis form is disordered (see figure at right). Since the helix is an important element of secondary structure in a wide range of functional proteins, this strategy for photo-control has found general application.
We are exploring new ways to employ this approach for controlling protein function
Trans-to-cis isomerization of an azobenzene cross-linker drives unfolding of an helical peptide.