Development of a polyvalent assay system for lead identification.
In an effort to identify new approaches to lead discovery a polyvalent assay was developed to allow identification of weak inhibitors. This approach involves the polyvalent display of a protein binder off a Tenta-gel scaffold and the generation of a polyvalent display of protein by biotinylation followed by complexation with fluorescently labeled streptavidin. Subsequent exposure of the streptavidin complexed protein to Tenta-gel beads with active protein binders results in fluorescent beads, which are easily viewed under a fluorescent microscope.
Lovering
Frank
F
Department of Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. flovering@wyeth.com
Angell
Yvonne
Y
Zhang
Yan-Ling
YL
Bridges
Kristie
K
D019921:Biotinylation; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry; D008024:Ligands; D008856:Microscopy, Fluorescence / Q000379:methods; D018716:Molecular Mimicry; D019000:Phosphotyrosine / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D019809:Streptavidin / Q000737:chemistry
D005456:Fluorescent Dyes; D008024:Ligands; D011137:Polystyrenes; C101297:Tentagel resin; D019000:Phosphotyrosine; D019809:Streptavidin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases