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 bas ic and applied research. Satisfactory display of a ligand for the acceptor protein is critical for successful binding to occur. Here we describe the a pplication of combinatorial chemistry to systematically explore the propert ies of linkers used to present peptide ligands to various protein targets, Our main interest is in drug discovery, and our results probably explain, i n large part, the disappointing efficiency of an early drug discovery metho d known as the "Selectide Process" (Lam, K. S., et al. (1991) Nature 358, 8 2-84). Interestingly, for all seven protein targets studied, a cationic fea ture 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 exc hange mechanisms. (C) 2000 Academic Press.