ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Bioprocess Engineering
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1597344
Design, Synthesis, and Anti-inflammatory Potential of PROTAC Drug Molecules Based on Fondaparinux Sodium
Provisionally accepted
- 1Beijing University of Chemical Technology, Beijing, China
- 2National Institute of Metrology, Beijing, Beijing Municipality, China
- 3Uppsala University, Uppsala, Uppsala, Sweden
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In this study, we used an approach by conjugating Fondaparinux Sodium (FS) with selected drugs to generate proteolysis-targeting chimeras (PROTACs). By applying bioprocess engineering principles, the direct amidation reaction was optimized-through precise control of pH, substrate ratios, and solvent selection-to reliably produce high-purity (>99%) PROTAC molecules on a scalable platform. Surface plasmon resonance (SPR) analysis demonstrated that the synthesized PROTACs exhibit micromolar binding affinities (KD ≈ 10⁻⁶ M) toward inflammatory mediators RANTES (CCL5) and interleukin-6 (IL-6). In vitro assays using peripheral blood mononuclear cells (PBMCs) revealed that two candidate compounds (Product 6 and Product 10) significantly inhibited lipopolysaccharide (LPS)induced interleukin-1β (IL-1β) release in a concentration-dependent manner, while FS and the drugs alone had no effect. These findings not only provide an innovative strategy for targeting "undruggable" proteins but also establish a robust, scalable process for the production of PROTAC-based antiinflammatory agents.
Keywords: Fondaparinux Sodium (FS)1, Proteolysis Targeting Chimera (PROTAC)2, targeted protein degradation3, Surface Plasmon Resonance (SPR)4, cytokine suppression5 ， anti-inflammatory6
Received: 21 Mar 2025; Accepted: 26 May 2025.
Copyright: © 2025 Wu, Zhang, Zhao, Maccarana, Li and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Tianji Zhang, National Institute of Metrology, Beijing, 100029, Beijing Municipality, China
Hui Cao, Beijing University of Chemical Technology, Beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.