Tuning Polyacrylate Composition to Recognize and Modulate Fluorescent Proteins

Authors:

Darwin C. Gomez, Swarnadeep Seth, Ronnie Mondal, Stephen J. Koehler, Jared G. Baker, Charles Plate, Ian C. Anderson, Mikayla R. Smith, Joey Gloriod, Morgan Gunter, Valerie V. Welborn,* Sanket A. Deshmukh, and C. Adrian Figg

Affiliation:

D. C. Gomez, R. Mondal, S. J. Koehler, J. G. Baker, I. C. Anderson, M. R. Smith, J. Gloriod, M. Gunter, V. V. Welborn, C. A. Figg Macromolecules Innovation Institute and Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA

D. C. Gomez, S. J. Koehler, J. G. Baker, I. C. Anderson, M. R. Smith, J. Gloriod, M. Gunter, C. A. Figg Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg,Virginia 24061, USA

D. C. Gomez Department of Chemistry, Eastern Visayas State University, Tacloban City 6500, Philippines

S. Seth, C. Plate, S. A. Deshmukh Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061, USA

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Description:

Molecular definition is usually regarded as a prerequisite to achieve protein recognition and functionalmodulation, particularly for macromolecular interactions. Herein, we report that polymers with specific combinations ofmonomers 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 andenhanced fluorescence by >100%. Purification of the polymerization product revealed subpopulations of compositionswith distinct affinities and selectivity for GFP over a competing protein. Experimental and computational binding analysesconfirmed that there are distinct RHO–GFP interactions, which are influenced by RHO chemical composition. Thesefindings show that sequence-defined structures are not a prerequisite for selective protein recognition. Synthetic polymerscan 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 orcomplex peptide scaffolds.

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Tags:

Polymers Protein

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File Name File Description File Type File Size File URL
Supplementary Information Experimental and simulation supporting information. docx 12.23 MB Login to download
Simulation Movies Movies on metadynamics simulations of oligomer-protein free energy landscapes. zip 43.51 MB Login to download