TANDEM-COLUMN CHROMATOGRAPHIC METHOD FOR STUDYING THE INTERACTION BETWEEN LIGANDS AND THEIR TARGETS - LIPOPOLYSACCHARIDE AS A MODEL

The identification of a lead ligand from a library of compounds for a specific target requires both a selection process and a method to asse ss relative affinities. Using a tandem-column chromatographic techniqu e, we have developed a novel and rapid method for determination of rel ative affinities for ligands binding to a specific target molecule. We demonstrate, using known ligands for the lipid A region of lipopolysa ccharide, that the relative affinities of these ligands can be determi ned and may be used to characterize the competitive interaction betwee n ligands for the same target. The method can be adapted toward screen ing of soluble libraries of peptides and small molecules and those lig ands exhibiting a desired affinity can be rapidly selected for further characterization/development. (C) 1995 Academic Press, Inc.