Multifunctional Protein-Polymer Conjugates via One-Pot, Oxygen-Tolerant Click Polymerization for In Vivo Drug Delivery

Voutyritsa et al. (2023) demonstrated simultaneous copper-mediated polymerization and click chemistry for protein-polymer conjugate synthesis. This idea extends the concept to engineer “one-pot” multifunctional conjugates in entirely oxygen-tolerant, aqueous conditions, incorporating both targeting ligands and therapeutic payloads via orthogonal click handles. Such conjugates could be tailored for specific disease markers (e.g., cancer cell surface antigens), with multiple functional modalities (imaging, therapy, targeting) built in. Unlike existing sequential conjugation or in vitro-only methods, this approach would enable scalable, streamlined production of personalized therapeutics that are robust and safe for in vivo use (see also Oprea & Smith, 2024). The integration of new click modalities (e.g., iminosydnones, SeNEx) could further expand the chemical diversity and functionality.

References:

1. Click Chemistry Methodology: The Novel Paintbrush of Drug Design. Ioana Oprea, T. K. Smith (2024). ACS Chemical Biology.
2. Design and Synthesis of Iminosydnones for Fast Click and Release Reactions with Cycloalkynes.. Margaux Riomet, E. Decuypère, K. Porte, Sabrina Bernard, L. Plougastel, S. Kolodych, D. Audisio, F. Taran (2018). Chemistry.
3. Synthesis of Multifunctional Protein-Polymer Conjugates via Oxygen-tolerant, Aqueous Copper-Mediated Polymerization and Bioorthogonal Click Chemistry.. Errika Voutyritsa, C. Gryparis, Alexis Theodorou, K. Velonia (2023). Macromolecular rapid communications.
4. Bioinspired Selenium-Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole-Scale Medicinal Chemistry and Bioconjugation.. Wei Hou, Yi-Ying Zhang, Fuchao Huang, Wanting Chen, Yuang Gu, Yan Wang, Jiacheng Pang, Hewei Dong, Kangyin Pan, Shuning Zhang, Peixiang Ma, Hongtao Xu (2024). Angewandte Chemie.