Abc Amino Acids: Design, Synthesis, and Properties of New Photoelastic Amino Acids

Photoisomerizable amino acids provide a direct avenue to the experimental manipulation of bioactive
polypeptides, potentially allowing real-time, remote control of biological systems and enabling useful
applications in nanobiotechnology. Herein, we report a new class of photoisomerizable amino acids
intended to cause pronounced expansion and contraction in the polypeptide backbone, i.e., to be
photoelastic. These compounds, termed Abc amino acids, employ a photoisomerizable azobiphenyl
chromophore to control the relative disposition of aminomethyl and carboxyl substituents. Molecular
modeling of nine Abc isomers led to the identification of one with particularly attractive properties,
including the ability to induce contractions up to 13 Å in the backbone upon trans → cis photoisomerization. This isomer, designated mpAbc, has substituents at meta and para positions on the inner (azo-linked) and outer rings, respectively. An efficient synthesis of Fmoc-protected mpAbc was executed in
which the biaryl components were formed via Suzuki couplings and the azo linkage was formed via
amine/nitroso condensation; protected forms of three other Abc isomers were prepared similarly. An
undecapeptide incorporating mpAbc was synthesized by conventional solid-phase methods and displayed
characteristic azobenzene photochemical behavior with optimal conversion to the cis isomer at 360 nm
and a thermal cis → trans half-life of 100 min at 80 °C.