Simeonov A, Matsushita M, Juban E A, Thompson E H, Hoffman T Z, Beuscher A E, Taylor M J, Wirsching P, Rettig W, McCusker J K, Stevens R C, Millar D P, Schultz P G, Lerner R A, Janda K D
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2000 Oct 13;290(5490):307-13. doi: 10.1126/science.290.5490.307.
The forte of catalytic antibodies has resided in the control of the ground-state reaction coordinate. A principle and method are now described in which antibodies can direct the outcome of photophysical and photochemical events that take place on excited-state potential energy surfaces. The key component is a chemically reactive optical sensor that provides a direct report of the dynamic interplay between protein and ligand at the active site. To illustrate the concept, we used a trans-stilbene hapten to elicit a panel of monoclonal antibodies that displayed a range of fluorescent spectral behavior when bound to a trans-stilbene substrate. Several antibodies yielded a blue fluorescence indicative of an excited-state complex or "exciplex" between trans-stilbene and the antibody. The antibodies controlled the isomerization coordinate of trans-stilbene and dynamically coupled this manifold with an active-site residue. A step was taken toward the use of antibody-based photochemical sensors for diagnostic and clinical applications.
