Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2018-07-07 , DOI: 10.1016/j.bmc.2018.07.011 Andrea Angeli , Marianne Kuuslahti , Seppo Parkkila , Claudiu T. Supuran
The activation of a α-class carbonic anhydrase (CAs, EC 4.2.1.1) from Trypanosoma cruzi (TcCA) was investigated with the best known classes of activators, the amino acids and aromatic/heterocyclic amines. The best TcCA activators were l-/d-DOPA and 4-amino-l-phenylalanine, which had activation constants in the range of 0.38–0.83 µM. Low micromolar activators were also l-/d-Trp, l-/d-Tyr, l-Gln, histamine and serotonin (KAs of 1.79–4.92 µM), whereas l-/d-His, l-/d-Phe and l-Asp were less effective activators (KAs of 6.39–18.7 µM). Amines such as dopamine, pyridyl-alkylamines, aminoethyl-piperazine or l-adrenaline, were devoid of activating effects on TcCA. Since the role of autacoids as many of these compounds investigated here is not known for the life cycle of T. cruzi, our work provides new tools for further investigations of factors connected with this protozoan pathogen infection.
中文翻译:
致病性原生动物克氏锥虫的α-碳酸酐酶的胺和氨基酸的激活研究
用最知名的活化剂,氨基酸和芳香族/杂环胺类化合物研究了克氏锥虫(TcCA)的α类碳酸酐酶(CAs,EC 4.2.1.1)的活化作用。最好的TcCA激活剂是1 - d dPA和4-氨基-1-苯丙氨酸,其激活常数在0.38–0.83 µM范围内。低微摩尔活化剂也升- / d -Trp,升- / d -Tyr,升-Gln,组胺和血清素(K甲的1.79-4.92小号μM),而升- / d -His,升- / d -苯丙氨酸和升-Asp不太有效的活化剂(K甲š6.39-18.7微米)。诸如多巴胺,吡啶基-烷基胺,氨乙基-哌嗪或1-肾上腺素的胺缺乏对TcCA的活化作用。由于自身活性物质如许多这些化合物的作用,研究这里的生命周期是不知道锥虫,我们的工作提供了与此原生动物病原体感染有关的因素进一步研究新的工具。