Combinatorial chemistry defines general properties of linkers for the optimal display of peptide ligands for binding soluble protein targets to TentaGel microscopic beads.
Affinity chromatography and the binding of soluble target proteins to novel or known ligands attached to solid supports are important phenomena to basic and applied research. Satisfactory display of a ligand for the acceptor protein is critical for successful binding to occur. Here we describe the application of combinatorial chemistry to systematically explore the properties of linkers used to present peptide ligands to various protein targets. Our main interest is in drug discovery, and our results probably explain, in large part, the disappointing efficiency of an early drug discovery method known as the "Selectide Process" (Lam, K. S., et al. (1991) Nature 358, 82-84). Interestingly, for all seven protein targets studied, a cationic feature was found to be a common theme for optimal linkers displaying peptide ligands on TentaGel beads, and this is not likely to be caused by ionic exchange mechanisms.
Thorpe
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Departments of Discovery Biology and Chemistry, Department of Analytical Chemistry, Selectide Corporation, 1580 E. Hanley Boulevard, Tucson, Arizona 85737, USA. david.thorpe@aventis.com
Walle
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D020650:Combinatorial Chemistry Techniques; D008024:Ligands; D010455:Peptides / Q000378:metabolism*; D011137:Polystyrenes; D011485:Protein Binding
D008024:Ligands; D010455:Peptides; D011137:Polystyrenes; C101297:Tentagel resin