Publication Date:
2000-10-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simeonov, A -- Matsushita, M -- Juban, E A -- Thompson, E H -- Hoffman, T Z -- Beuscher, A E 4th -- 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 -- AI39089/AI/NIAID NIH HHS/ -- GM43858/GM/NIGMS NIH HHS/ -- P01CA27489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 13;290(5490):307-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11030644" target="_blank"〉PubMed〈/a〉
Keywords:
Antibodies, Catalytic/*chemistry
;
Antibodies, Monoclonal/*chemistry
;
Binding Sites
;
Binding Sites, Antibody
;
Chemistry, Physical
;
Crystallography, X-Ray
;
*Fluorescence
;
Haptens
;
Ligands
;
Microscopy, Fluorescence
;
Models, Chemical
;
Models, Molecular
;
Photochemistry
;
Physicochemical Phenomena
;
Spectrometry, Fluorescence
;
Stereoisomerism
;
Stilbenes/*chemistry/*immunology
;
Temperature
;
Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
