Abstract:

Can a synthetic polymer mimic the exquisite selectivity and affinity of natural antibodies? Synthetic antibodies (SAs)—also referred to as “plastic antibodies”—are lightly cross-linked hydrogel nanoparticles designed to bind specific biological macromolecules. These particles are synthesized via aqueous free-radical copolymerization of diverse functional  monomers at elevated temperatures (~65 °C), yielding stable colloidal suspensions with tunable sizes from 30 to over 250 nm. By screening a small, compositionally diverse library of these nanoparticles against a target protein or peptide epitope, initial “hit” binders can be identified. These hits provide insight into monomer functionalities critical for target interaction. Affinity and selectivity are then optimized through directed synthetic evolution—iterative modification of monomer composition—to generate high-performance binding particles.                   

Despite their statistical monomer distribution and inhomogeneous internal structure, SAs consistently demonstrate nanomolar to low micromolar affinity and specificity toward target proteins and peptides. Their low-density, carbon-based matrix features internal mesh sizes (>15 nm) that permit macromolecular access and enable multivalent binding interactions within the particle interior.  This platform has yielded synthetic affinity reagents for a wide range of applications, including:                                                                                                      

• Inhibition of vascular endothelial growth factor (VEGF165) to suppress tumor growth in vivo

• Systemic clearance of peptide toxins in murine models

• Sepsis intervention through targeted neutralization of circulating inflammatory mediators

• Broad-spectrum snake antivenoms

• Therapeutic agents for ischemic stroke via modulation of cerebral perfusion

Beyond biomedical applications, SAs have also been developed as affinity media for protein purification and analysis, and as selective recognition elements for environmental and agricultural targets such as insecticidal proteins.

Together, these results suggest that synthetic polymers—despite lacking biological sequence information—can be rationally engineered to function as antibody mimics, expanding the toolkit for molecular recognition in both therapeutic and analytical contexts.

Event Description: 

Professor Kenneth J. Shea will be this year’s recipient of the Tolman Medal. “The Tolman Medal is awarded each year by the Southern California Section of the American Chemical Society in recognition of outstanding contributions to chemistry. These contributions may include achievements in fundamental studies; achievements in chemical technology; significant contributions to chemical education; or outstanding leadership in science on a national level. The nominee need not be a Southern California resident; however, most of the award-related accomplishments must have been made in this area.”

Congratulations to Professor Shea on this wonderful and well-deserved honor!

The Tolman ceremony will be held on June 11, 2025 at the Beckman Center. Tickets are required for this event. Registration is now closed.