New Efficient Substrates for Semicarbazide-Sensitive Amine Oxidase/VAP-1 Enzyme: Analysis by SARs and Computational Docking

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• 作者：Francesc Yraola ; Silvia Garc&iacute ; a-Vicente ; Juan Ferná ; ndez-Recio ; Fernando Albericio ; Antonio Zorzano ; Luc Marti ; Miriam Royo
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：October 19, 2006
• 年：2006
• 卷：49
• 期：21
• 页码：6197 - 6208
• 全文大小：355K
• 年卷期：v.49,no.21(October 19, 2006)
• ISSN：1520-4804

文摘

Structure activity relationships for semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) were studied using a library of arylalkylamine substrates, with the aim of contributing to the discoveryof more efficient SSAO substrates. Experimental data were contrasted with computational docking studies,thereby allowing us to examine the mechanism and substrate-binding affinity of SSAO and thus contributeto the discovery of more efficient SSAO substrates and provide a structural basis for their interactions. Wealso built a model of the mouse SSAO structure, which provides several structural rationales for interspeciesdifferences in SSAO substrate selectivity and reveals new trends in SSAO substrate recognition. In thiscontext, we identified novel efficient substrates for human SSAO that can be used as a lead for the discoveryof antidiabetic agents.