Selection and amplification of hosts from dynamic combinatorial libraries of macrocyclic disulfides

Abstract

We have discovered two receptors for two different guests from a single dynamic combinatorial library. Each of the two guests amplifies the formation of a tightly binding host at the expense of unfit library members. Small differences in host-guest binding translate into useful differences in amplification. The selected hosts could be readily synthesized using biased dynamic libraries that contain only the right ratio of those building blocks that were selected by the guests. These results establish dynamic combinatorial chemistry as a practical method not only for the discovery but also for the synthesis of new receptors.