title: New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme: analysis by SARs and computational docking.
abstract: 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 discovery of 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 contribute to the discovery of more efficient SSAO substrates and provide a structural basis for their interactions. We also built a model of the mouse SSAO structure, which provides several structural rationales for interspecies differences in SSAO substrate selectivity and reveals new trends in SSAO substrate recognition. In this context, we identified novel efficient substrates for human SSAO that can be used as a lead for the discovery of antidiabetic agents.
authors.affiliation: Combinatorial Chemistry Unit and Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1, E-08028-Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Yraola
authors.forename: Silvia
authors.initials: S
authors.lastname: García-Vicente
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.forename: Luc
authors.initials: L
authors.lastname: Marti
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology; D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D016208:Databases, Factual; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013379:Substrate Specificity
chemical_list: D001596:Benzylamines; D015815:Cell Adhesion Molecules; D007004:Hypoglycemic Agents; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse; D005947:Glucose