Anton Simeonov,¹ Masayuki Matsushita,¹ Eric A. Juban,² Elizabeth H. Z. Thompson,³ Timothy Z. Hoffman,¹ Albert E. Beuscher IV¹² Matthew J. Taylor,¹ Peter Wirsching,¹ Wolfgang Rettig,⁴ James K. McCusker,² Raymond C. Stevens,³ David P. Millar,³ Peter G. Schultz,¹ Richard A. Lerner,¹ Kim D. Janda¹

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.

¹ Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
² Department of Chemistry, University of California Berkeley, Berkeley, CA 94720-1460, USA.
³ Department of Molecular Biology, The Scripps Research Institute, 10555 North Torrey Pines Road, La Jolla, CA 92037, USA.
⁴ Institute of Physical and Theoretical Chemistry, Humboldt-University Berlin, Bunsenstrasse 1 D-10117 Berlin, Germany.