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Journal of Biomolecular Screening
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Complex Gel Permeation Assays for Screening Combinatorial Libraries

Mark E. Schurdak

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Martin J. Voorbach

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Lan Gao

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Xueheng Cheng

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Kenneth M. Comess

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Susan M. Rottinghaus

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Usha Warrior

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Hoa N. Truong

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

David J. Burns

Department of Biological Screening, Abbott Laboratories, Abbott Park, IL

Bruce A. Beutel

Infectious Disease Research, Abbott Laboratories, Abbott Park, IL

Gel permeation methods have been commonly used to screen combinatorial libraries synthesized on a solid support. We report here three screens of combinatorial libraries using gel permeation assays. These include a simple enzymatic assay to identify inhibitors of the influenza enzyme neuraminidase, and two more complex assays designed to screen for inhibitors of the interleukin-8 (IL-8)-IL-8 receptor and the urokinase-urokinase receptor interactions, respectively. The IL-8 ligand-receptor assay makes use of IL-8 receptor-expressing cells attached to a membrane, thus enabling washing steps as part of the assay. The urokinase ligand-receptor assay employs an enzyme-linked immunosorbent assay-type format, previously thought to be amenable only to well-based assays. The results of these three screens are reported here, including the discovery of a novel series of acyclic inhibitors of neuraminidase. The development of complex assays in a gel permeation format allows for the routine screening of combinatorially as well as noncombinatorially made compound collections against virtually any kind of target, and is being widely used in our high throughput screening operations.

Journal of Biomolecular Screening, Vol. 6, No. 5, 313-323 (2001)
DOI: 10.1177/108705710100600505
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