Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Faculty of Medicine and Life Sciences, University of Tampere, Fimlab Ltd., Tampere University Hospital, 33520 Tampere, Finland.
Bioorg Med Chem. 2018 Aug 7;26(14):4187-4190. doi: 10.1016/j.bmc.2018.07.011. Epub 2018 Jul 7.
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 (Ks of 1.79-4.92 µM), whereas l-/d-His, l-/d-Phe and l-Asp were less effective activators (Ks 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.
本研究考察了α类碳酸酐酶（CA，EC 4.2.1.1）的激活作用，所用的激活剂是最常见的氨基酸类和芳香族/杂环胺类。最佳的 TcCA 激活剂为 l-/d-DOPA 和 4-氨基-l-苯丙氨酸，其激活常数在 0.38-0.83µM 范围内。低微摩尔级的激活剂还有 l-/d-Trp、l-/d-Tyr、l-Gln、组氨酸和 5-羟色胺（Ks 值为 1.79-4.92µM），而 l-/d-His、l-/d-Phe 和 l-Asp 的激活效果较差（Ks 值为 6.39-18.7µM）。像多巴胺、吡啶基-烷基胺、氨基乙基-哌嗪或 l-肾上腺素这样的胺类化合物对 TcCA 没有激活作用。由于这些化合物中的许多化合物在 T. cruzi 的生命周期中的作用尚不清楚，我们的工作为进一步研究与这种原生动物病原体感染相关的因素提供了新的工具。
