Polyacrylates with protein recognition and functional modulation

Molecular definition is usually regarded as a prerequisite to achieve protein recognition and functional modulation, particularly for macromolecular interactions. Herein, we report that polyacrylates with specific combinations of monomers arranged into random sequences (random hetero oligomers (RHOs)) are capable of binding to a model green fluorescent protein (GFP) with nanomolar affinity, resulting in fluorescence increases >50%. Purification methods show that within a single polymerization product, there are subpopulations of compositions with varying affinity for GFP and selectivity for GFP over a competing protein. Further experimental and computational binding analyses showed there are distinct RHO-GFP interactions according to RHO chemical composition. These results demonstrate that readily accessible polymerization methods can be used to develop protein modulators, where sequence definition is not a necessity.