Tuning Polyacrylate Composition to Recognize and Modulate Fluorescent Proteins

D Darwin C. Gomez (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) S Swarnadeep Seth (Department of Chemical Engineering Virginia Tech Blacksburg Virginia 24061 USA) R Ronnie Mondal (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) S Stephen J. Koehler (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) J Jared G. Baker (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) C Charles Plate (Department of Chemical Engineering Virginia Tech Blacksburg Virginia 24061 USA) I Ian C. Anderson (Hawkesbury Institute for the Environment, Western Sydney University) M Mikayla R. Smith (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) J Joey Gloriod (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) M Morgan Gunter (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) V Valerie V. Welborn (Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA) S Sanket A. Deshmukh (Department of Chemical Engineering) C C. Adrian Figg (Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States)

Abstract

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.

Article Details

Volume / Issue Vol. 65, Issue 2
Published January 09, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

D

Darwin C. Gomez

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

S

Swarnadeep Seth

Department of Chemical Engineering Virginia Tech Blacksburg Virginia 24061 USA

R

Ronnie Mondal

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

S

Stephen J. Koehler

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

J

Jared G. Baker

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

C

Charles Plate

Department of Chemical Engineering Virginia Tech Blacksburg Virginia 24061 USA

I

Ian C. Anderson

Hawkesbury Institute for the Environment, Western Sydney University

M

Mikayla R. Smith

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

J

Joey Gloriod

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

M

Morgan Gunter

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

V

Valerie V. Welborn

Macromolecules Innovation Institute and Department of Chemistry Virginia Tech Blacksburg Virginia 24061 USA

S

Sanket A. Deshmukh

Department of Chemical Engineering

C

C. Adrian Figg

Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States