New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme: analysis by SARs and computational docking.
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.
Yraola
Francesc
F
Combinatorial Chemistry Unit and Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1, E-08028-Barcelona, Spain.
García-Vicente
Silvia
S
Fernandez-Recio
Juan
J
Albericio
Fernando
F
Zorzano
Antonio
A
Marti
Luc
L
Royo
Miriam
M
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
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