Polymer-protein conjugates significantly improve the bioavailability of therapeutic proteins; however, systematic evaluations of how distinct structural parameters of polymers effect the bioactivities of the conjugated proteins remain challenging due to the formation of a heterogeneous mixture of final conjugates using polymers with dispersity (e.g., PEG, etc.). To solve this long-standing problem, we developed a new class of discrete polymer-protein conjugates with full control over the conjugation site on proteins and structural parameters of the conjugated polymers, which were synthesized via an efficient, scalable, and convergent strategy–iterative exponential growth (IEG)–for obtaining polymers with defined stereochemistry, length, rigidity, and functionality. The uniform construction of our discrete polymer-protein conjugates enabled systematic evaluation of the structural impact on protein bioactivities and provided a new approach of controlling biomaterial properties. Therefore, it could potentially serve as a guidance for future protein conjugates drug design to achieve high therapeutic efficacy and excellent long-term stability.

Explorations of discrete polymer platforms for evaluating the structure-property relationship of polymer-protein conjugates

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.