Identifying modulators of protein-protein interactions using photonic crystal biosensors.
Inhibitors and activators of protein-protein interactions are valuable as biological probes and medicinal agents but are often difficult to identify. Herein we describe a high-throughput assay, based upon photonic crystal (PC) biosensors, for the identification of modulators of protein-protein interactions. Through the use of a d-biotin-tris-NTA (BTN) hybrid compound, any His6-tagged protein can be immobilized on the surface of a PC biosensor. Binding of the bound protein to its cognate partner is detected via a shift in the peak wavelength value. We demonstrate this assay with three protein-protein pairs (caspase-9-XIAP, caspase-7-XIAP, FKBP12-FRB) and their small molecule modulators.
Heeres
James T
JT
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA.
Kim
Seok-Ho
SH
Leslie
Benjamin J
BJ
Lidstone
Erich A
EA
Cunningham
Brian T
BT
Hergenrother
Paul J
PJ
D015374:Biosensing Techniques / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D055767:Immobilized Proteins; D055095:Optics and Photonics / Q000379:methods; D011485:Protein Binding / Q000187:drug effects*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D055767:Immobilized Proteins; D011506:Proteins