Tuning Polyacrylate Composition to Recognize and Modulate Fluorescent Proteins

Abstract

Molecular definition is usually regarded as a prerequisite to achieve protein recognition and functional modulation, particularly for macromolecular interactions. Herein, we report that polymers with specific combinations of monomers arranged into random sequences [random hetero oligomers (RHOs)] can selectively bind to a model protein. Using green fluorescent protein (GFP) as a target, polyacrylates were developed that bound with nanomolar affinity and enhanced fluorescence by >100%. Purification of the polymerization product revealed subpopulations of compositions with distinct affinities and selectivity for GFP over a competing protein. Experimental and computational binding analyses confirmed that there are distinct RHO–GFP interactions, which are influenced by RHO chemical composition. These findings show that sequence-defined structures are not a prerequisite for selective protein recognition. Synthetic polymers can instead serve as scalable, tunable platforms for molecular recognition—representing a significant leap towards next-generation sensing, therapeutic, responsive, and catalytic materials in domains previously dominated by biologics or complex peptide scaffolds.