Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Lenin Hills 1, Bldg. 40, Moscow 119991, Russia.
Centre for Strategic Planning of FMBA of the Russian Federation, Pogodinskaya St., Bldg. 10, Moscow 119121, Russia.
Molecules. 2023 Aug 22;28(17):6178. doi: 10.3390/molecules28176178.
Biomedical studies of the role of organic selenium compounds indicate that the amino acid derivative of L-selenomethionine, α-ketomethylselenobutyrate (KMSB), can be considered a potential anticancer therapeutic agent. It was noted that, in addition to a direct effect on redox signaling molecules, α-ketoacid metabolites of organoselenium compounds are able to change the status of histone acetylation and suppress the activity of histone deacetylases in cancer cells. However, the wide use of KMSB in biomedical research is hindered not only by its commercial unavailability, but also by the fact that there is no detailed information in the literature on possible methods for the synthesis of this compound. This paper describes in detail the procedure for obtaining a high-purity KMSB preparation (purity ≥ 99.3%) with a yield of the target product of more than 67%. L-amino acid oxidase obtained from was used as a catalyst for the conversion of L-selenomethionine to KMSB. If necessary, this method can be used as a basis both for scaling up the synthesis of KMSB and for developing cost-effective biocatalytic technologies for obtaining other highly purified drugs.
有机硒化合物的生物医学研究表明，L-硒代蛋氨酸的氨基酸衍生物α-酮甲基硒代丁酸盐（KMSB）可以被认为是一种有潜力的抗癌治疗剂。研究还指出，除了对氧化还原信号分子的直接作用外，有机硒化合物的α-酮酸代谢物能够改变组蛋白乙酰化状态，并抑制癌细胞中组蛋白去乙酰化酶的活性。然而，KMSB 在生物医学研究中的广泛应用不仅受到其商业上不可用的限制，还因为文献中没有关于合成这种化合物的可能方法的详细信息。本文详细描述了一种获得高纯度 KMSB 制剂（纯度≥99.3%）的方法，该方法的目标产物收率超过 67%。本文使用从 中获得的 L-氨基酸氧化酶作为将 L-硒代蛋氨酸转化为 KMSB 的催化剂。如果需要，该方法既可以作为 KMSB 合成放大的基础，也可以作为开发其他高纯度药物的经济有效的生物催化技术的基础。
