Design, Synthesis, and Biological Activity of (E)‑α-Fluorovinylphosphonate-Based Reversible Cathepsin C Inhibitors

In this study, we describe the synthesis of novel dipeptide analogs of (E)-α-fluorovinylphosphonates, with a key step involving the Horner–Wadsworth–Emmons (HWE) reaction. The synthesized compounds were evaluated as potential reversible inhibitors of the cathepsin C enzyme. Comprehensive characterization of the target molecules was performed, and their inhibitory activity was assessed. Additionally, molecular docking studies were conducted to elucidate the binding interactions of the synthesized derivatives within the cathepsin C active site. The results highlight promising structural features for the design of effective enzyme inhibitors and provide a foundation for further optimization of fluorovinylphosphonate-based dipeptides.

本研究报道了(E)-α-氟乙烯基膦酸酯类新型二肽类似物的合成方法，其关键步骤采用霍纳尔-沃兹沃思-埃蒙斯（Horner–Wadsworth–Emmons, HWE）反应。所合成的化合物被评估为组织蛋白酶C（cathepsin C）的潜在可逆抑制剂。研究对目标分子进行了全面的结构表征，并测定了其抑制活性。此外，本研究还开展了分子对接实验，以阐明所合成衍生物在组织蛋白酶C活性位点内的结合相互作用。研究结果凸显了可用于设计高效酶抑制剂的极具潜力的结构特征，同时为基于氟乙烯基膦酸酯的二肽类化合物的后续优化提供了坚实的理论基础。