Document Type
Article
Publication Date
1-8-2026
Publication Title
ACS Omega
Abstract
Combinatorial methods for preparing polymeric biomaterials enable the rapid identification of materials useful for many applications in science, medicine, and engineering. In the work described here, we demonstrate that side-chain reactive polymers can be used as templates for the rapid preparation of a small library of diversely functionalized protein–polymer conjugates. The activated ester polymer poly(pentafluorophenyl acrylate) (PPFPA) was modified postpolymerization with substoichiometric equivalents of three hydrophilic primary amines to yield a library of amphiphilic, side-chain reactive copolymers. These copolymers were then conjugated to two receptor-targeting proteins, holotransferrin (hTF) and an engineered fibronectin-based protein (Fn3), through amine-activated ester coupling. We investigated the influence of polymer:protein ratio, side-chain chemistry (i.e., hydrophilic group identity and number of protein-reactive groups), and protein identity on conjugation efficiencies. Our results demonstrate that, for polymers of similar solubility in aqueous media, a larger polymer:protein ratio yields higher conjugation efficiencies. In addition, polymers with a greater number of reactive groups or shorter hydrophilic side chains improve protein conjugation efficiency. Finally, smaller proteins couple to the polymers more efficiently than do larger proteins. Collectively, the results described here demonstrate a modular approach for efficiently preparing bioconjugates with diverse chemistries that may be of interest in a broad range of applications.
Keywords
Conjugate Acid-Base Pairs, Conjugated Polymers, Functionalization, Molecular Properties, Polymers
Volume
11
Issue
3
First Page
3926
Last Page
3936
DOI
https://doi.org/10.1021/acsomega.5c07215
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Rights
© 2026 The Authors. Published by American Chemical Society
Version
Version of Record
Recommended Citation
Kish, Emily W.; Lee, Thatcher M.; Ziemba, Alexis M.; Boamah, Ama; Figueroa, Bianca; Piccardi, Margherita; Dougan, Carey E.; Moore, Sarah J.; and Buck, Maren E., "Combinatorial Synthesis of Protein-Polymer Conjugates by Post-Polymerization Modification of Poly(Pentafluorophenyl Acrylate)s" (2026). Chemistry: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/chm_facpubs/101