Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
J Med Chem. 2023 Feb 9;66(3):1778-1789. doi: 10.1021/acs.jmedchem.2c01616. Epub 2023 Jan 19.
Unfractionated heparin (UFH) and enoxaparin (Enox) were substituted with a photoswitch (PS) showing quantitative and photoisomerizations. Long half-life of the photoisomer enabled comparison of the properties of heparins substituted with both PS photoisomers. Hydrodynamic diameter, , of UFH-PS decreased upon photoisomerization, the change being more pronounced for UFH-PS with a higher degree of substitution (DS), while of Enox-PS did not significantly change. The anticoagulative properties of substituted heparins were significantly attenuated compared to non-substituted compounds. The interaction of UFH-PS with HSA, lysozyme, and protamine was studied with ITC. Under serum-free conditions, UFH-PS- with a high DS stimulated proliferation of murine fibroblasts, while UFH-PS- decreased the viability of these cells. Under serum conditions, both UFH-PS- and UFH-PS- decreased cell viability, the reduction for UFH-PS- being higher than that for UFH-PS-. Neither Enox-PS- nor Enox-PS- influenced the viability at concentrations prolonging aPTT, while at higher concentrations their cytotoxicity did not differ.
未分级肝素 (UFH) 和依诺肝素 (Enox) 被一种光开关 (PS) 取代，表现出定量和光异构化。光异构体的长半衰期使具有两种 PS 光异构体取代的肝素的性质能够进行比较。UFH-PS 的流体力学直径 随着光异构化而减小，取代度 (DS) 较高的 UFH-PS 的变化更为明显，而 Enox-PS 的 则没有明显变化。与非取代化合物相比，取代肝素的抗凝特性明显减弱。用 ITC 研究了 UFH-PS 与 HSA、溶菌酶和鱼精蛋白的相互作用。在无血清条件下，高 DS 的 UFH-PS-刺激小鼠成纤维细胞增殖，而 UFH-PS-降低这些细胞的活力。在血清条件下，UFH-PS- 和 UFH-PS- 均降低细胞活力，UFH-PS- 的降低幅度高于 UFH-PS-。在延长 aPTT 的浓度下，Enox-PS- 和 Enox-PS- 均不影响细胞活力，而在更高的浓度下，它们的细胞毒性没有差异。
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