Selection of DNA-binding compounds via multistage molecular evolution

Combinatorial libraries incorporating multiple equilibria offer opportunities to study molecular evolution, and are a novel method of identifying ligands for biological receptors. We describe the construction and evaluation of a multi-equilibrium combinatorial library, in which structural diversity and structural mutation are accomplished via reversible imine formation and transition-metal complexation. We demonstrate that oligo d(A·T)-cellulose resin can select subsets of this libray, in accord with measured solution-phase affinities.