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Synthesis Coupled to Scintillation Proximity Affinity Screening

IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037-1031

Sue K. Knowles

IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037-1031

Xiao-Yi Xiao

IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037-1031

Chanfeng Zhao

IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037-1031

Gary S. David

Impact Enterprises, 9477 Poole St., La Jolla, CA 92037

Michael P. Nova

IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037-1031

The rapidly changing developments in genomics and combinatorial chemistry, generating new drug targets and large numbers of compounds, are beginning to push the limits of screening efficiently. Thus, there is a need for novel tools and strategies to improve high throughput screening. A novel approach is to couple synthesis and screening on a common platform, rather than to increase the rate at which traditional screening methods can be implemented. We have developed a proprietary grafted polymer with special fluorescence characteristics referred to as Electronically Encoded Fluorescence matriX (EFX^TM), which has the sturdiness and required functionality for direct chemical synthesis as well as suitable surface characteristics for measuring interactions in aqueous solution. This matrix is fabricated into a MicroTube reactor, and each tube is associated with an electronically encoded tag. The system follows a homogenous assay protocol and is based on the scintillation proximity principle. Using solid-phase chemistry, a variety of small molecules may be synthesized onto the EFX. A simple binding assay can be conducted by combining a collection of MicroTubes with any radiolabeled acceptor molecule. The MicroTubes that carry active compounds are selected based on the photon mission or fluorescence characteristics. We validated this approach by evaluating the interactions of biotin with radiolabeled streptavidin.

Journal of Biomolecular Screening, Vol. 3, No. 4, 293-298 (1998)
DOI: 10.1177/108705719800300408


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