Blue-fluorescent antibodies.
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.
Simeonov
A
A
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Matsushita
M
M
Juban
E A
EA
Thompson
E H
EH
Hoffman
T Z
TZ
Beuscher
A E
AE
Taylor
M J
MJ
Wirsching
P
P
Rettig
W
W
McCusker
J K
JK
Stevens
R C
RC
Millar
D P
DP
Schultz
P G
PG
Lerner
R A
RA
Janda
K D
KD
D017151:Antibodies, Catalytic / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001665:Binding Sites; D001666:Binding Sites, Antibody; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D005453:Fluorescence; D006241:Haptens; D008024:Ligands; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D008958:Models, Molecular; D010777:Photochemistry; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry* / Q000276:immunology*; D013696:Temperature; D014466:Ultraviolet Rays
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D006241:Haptens; D008024:Ligands; D013267:Stilbenes