Yraola Francesc, Zorzano Antonio, Albericio Fernando, Royo Miriam
Swiss Federal Institute of Technology Zürich, Switzerland.
ChemMedChem. 2009 Apr;4(4):495-503. doi: 10.1002/cmdc.200800393.
Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) substrates show insulin-mimetic effects and are therefore potentially valuable molecules for the treatment of diabetes mellitus. Herein we review several structural and electronic aspects of SSAO arylalkylamine-based substrates. Two main modifications directly affect amine oxidase (AO) activity: 1) variation in ring substitution modulates the biological activity of the arylalkylamine ligand by converting a substrate into a substrate-like inhibitor, and 2) variation in the number of methylene units between the aromatic ring and the ammonium groups of the arylalkylamine substrates dramatically alters the oxidation rate between species. Furthermore, we review relevant information about mammalian SSAO/VAP-1 substrate selectivity and specificity over monoamine oxidases (MAOs).
氨基脲敏感性胺氧化酶/血管黏附蛋白-1（SSAO/VAP-1）底物具有胰岛素模拟作用，因此是治疗糖尿病潜在的有价值分子。在此，我们综述了基于芳基烷基胺的SSAO底物的几个结构和电子方面。有两种主要修饰直接影响胺氧化酶（AO）活性：1）环取代的变化通过将底物转化为类似底物的抑制剂来调节芳基烷基胺配体的生物活性；2）芳基烷基胺底物的芳香环与铵基团之间亚甲基单元数量的变化极大地改变了不同物种间的氧化速率。此外，我们还综述了关于哺乳动物SSAO/VAP-1底物相对于单胺氧化酶（MAO）的选择性和特异性的相关信息。
