Comparison of Affinity Ranking by Target-directed Dynamic Combinatorial Chemistry and Surface Plasmon Resonance

Target-directed dynamic combinatorial chemistry (tdDCC) is a powerful method to screen ligands for pharmacologically relevant targets. Generating a dynamic library from reversibly reacting building blocks in the presence of a target protein leads to the amplification of the most potent library constituents. In previous studies on tdDCC, these compounds were identified in a qualitative “hit/no-hit”-manner. However, the precise relationship between the degree of amplification and the affinity of the library constituent has not yet been evaluated. To study the amplification–affinity relationship, we compared tdDCC experiments, employing reversible acylhydrazone formation and the bacterial adhesin FimH as a target, with affinities of the library constituents as determined by surface plasmon resonance.