Institut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
J Med Chem. 2011 Mar 10;54(5):1170-7. doi: 10.1021/jm101284a. Epub 2011 Feb 3.
Lipoic acid moieties were attached to amine or amino acids showing activating properties against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The obtained lipoic acid conjugates of histamine, L-histidine methyl ester, and L-carnosine methyl ester were attached to gold nanoparticles (NPs) by reaction with Au(III) salts in reducing conditions. The CA activators (CAAs)-coated NPs showed low nanomolar activation (K(A)s of 1-9 nM) of relevant cytosolic, membrane-bound, mitochondrial, and transmembrane CA isoforms, such as CA I, II, IV, VA, VII, and XIV. These NPs also effectively activated CAs ex vivo, in whole blood experiments, with an increase of 200-280% of the CA activity. This is the first example of enzyme activation with nanoparticles and may lead to biomedical applications for conditions in which the CA activity is diminished, such as aging, Alzheimer's disease, or CA deficiency syndrome.
巯基乙酸部分被连接到具有激活锌酶碳酸酐酶（CA，EC 4.2.1.1）性质的胺或氨基酸上。组胺、L-组氨酸甲酯和 L-肉碱甲酯的所得巯基乙酸缀合物通过在还原条件下与 Au(III)盐反应而连接到金纳米粒子（NPs）上。CA 激活剂（CAAs）-涂覆的 NPs 对相关的细胞质、膜结合、线粒体和跨膜 CA 同工型表现出低纳摩尔激活（K(A)s 为 1-9 nM），例如 CA I、II、IV、VA、VII 和 XIV。这些 NPs 还可以在全血实验中有效地激活 CA，CA 活性增加 200-280%。这是纳米粒子酶激活的第一个例子，可能会为 CA 活性降低的情况（如衰老、阿尔茨海默病或 CA 缺乏综合征）开辟生物医学应用。
