Generation of Dynamic Combinatorial Libraries Using Hydrazone-Functionalized Surface Mimetics

Dynamic combinatorial chemistry (DCC) represents an approach, whereby traditional supramolecular scaffolds used for protein surface recognition might be exploited to achieve selective high affinity target recognition. Synthesis, in situ screening and amplification under selection pressure allows the generation of ligands, which bear different moieties capable of making multivalent non-covalent interactions with target proteins. Generic tetracarboxyphenyl porphyrin scaffolds bearing four hydrazide moieties have been used to form dynamic combinatorial libraries (DCLs) using aniline-catalyzed reversible hydrazone exchange reactions, in 10% DMSO, 5 mm NH4OAc, at pH 6.75. High resolution mass spectrometry (HRMS) was used to monitor library composition and establish conditions under which equilibria were established.