Freitas Humberto F, Pires Acássia Benjamim Leal, Castilho Marcelo S
Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, 40170-290, Brazil.
Programa de pós-graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santanta, BA, 44036-900, Brazil.
Mol Biotechnol. 2018 Apr;60(4):271-278. doi: 10.1007/s12033-018-0069-4.
Among the neglected tropical diseases, leishmaniasis stands out for its worldwide distribution and diversity of symptoms. Cutaneous leishmaniasis (CL), for instance, is endemic in 18 countries, but the available drugs to fight it have high toxicity and low patient adherence. In order to overcome this, dilemma drugs that target enzymes which are absent in the human host, such as Leishmania braziliensis sterol C24-methyltransferase (SMT-C24, EC 2.1.1.41), are needed. However, medicinal chemistry efforts toward this goal have been hampered by the low yield of soluble recombinant SMT-C24 afforded by currently available expression systems. Herein, we show that a combination of molecular biology and chromatographic strategies may increase the yield of LbSMT-C24 in up to fivefold. These results lay the ground for future investigation of this enzyme as a drug target.
在被忽视的热带疾病中，利什曼病因其在全球的分布范围和症状多样性而格外突出。例如，皮肤利什曼病（CL）在18个国家呈地方性流行，但用于治疗该病的现有药物毒性高且患者依从性低。为了克服这一难题，需要研发针对人类宿主中不存在的酶的药物，比如巴西利什曼原虫甾醇C24-甲基转移酶（SMT-C24，EC 2.1.1.41）。然而，目前可用的表达系统所提供的可溶性重组SMT-C24产量较低，阻碍了针对这一目标的药物化学研究工作。在此，我们表明分子生物学和色谱策略相结合可使巴西利什曼原虫SMT-C24的产量提高多达五倍。这些结果为未来将该酶作为药物靶点的研究奠定了基础。
