de Jesus Catarina Sofia Henriques, Enache Teodor Adrian, Diculescu Victor Constantin
Laboratory of Electroanalysis and Corrosion, Instituto Pedro Nunes, Coimbra, Portugal.
National Institute of Material Physics, Atomistilor 405A, 077125 Magurele, Romania.
J Electroanal Chem (Lausanne). 2020 Dec 1;878:114733. doi: 10.1016/j.jelechem.2020.114733. Epub 2020 Sep 30.
The ubiquitin-proteasome system regulates the level of proteins within cells through controlled proteolysis. In some diseases, the system function is dysregulated turning the ubiquitin-proteasome complex into a target for drug development. The redox behavior of proteasome inhibitors, epoxyketone and boronated peptides carfilzomib, oprozomib and delanzomib was investigated by voltammetric methods using glassy carbon and boron doped diamond electrodes. It was showed that the oxidation of epoxyketone peptides carfilzomib and oprozomib occurred in one step at glassy carbon electrode surface while at boron doped diamond two consecutive charge transfer reactions due to different adsorption orientation at the electrode surface were observed. The moieties of these peptides, involved in the oxidation process, were morpholine for carfilzomib and thiazole for oprozomib. For the boronated peptide delanzomib, two irreversible and independent redox processes, oxidation at +0.80 V and reduction at -1.40 V were identified in neutral media at both electrodes. The oxidation reaction occurred at the amino group close to the pyridine moiety of delanzomib with the transfer of one electron and one proton whereas the reduction process takes place at pyridine ring in a two-electrons two-protons mechanism. Redox mechanisms were proposed and the implications on the proteasome inhibition discussed.
泛素 - 蛋白酶体系统通过可控的蛋白水解作用调节细胞内蛋白质的水平。在某些疾病中，该系统功能失调，使得泛素 - 蛋白酶体复合物成为药物开发的靶点。使用玻碳电极和硼掺杂金刚石电极，通过伏安法研究了蛋白酶体抑制剂环氧酮和硼化肽卡非佐米、奥布佐米和德兰佐米的氧化还原行为。结果表明，环氧酮肽卡非佐米和奥布佐米在玻碳电极表面一步发生氧化，而在硼掺杂金刚石电极上，由于电极表面不同的吸附取向，观察到两个连续的电荷转移反应。这些肽参与氧化过程的部分，卡非佐米是吗啉环，奥布佐米是噻唑环。对于硼化肽德兰佐米，在两个电极的中性介质中都鉴定出两个不可逆且独立的氧化还原过程，在 +0.80 V 处氧化，在 -1.40 V 处还原。氧化反应发生在靠近德兰佐米吡啶部分的氨基上，转移一个电子和一个质子，而还原过程以双电子双质子机制在吡啶环上发生。提出了氧化还原机制并讨论了其对蛋白酶体抑制的影响。
