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Structure–Activity Relationships of SSAO/VAP‐1 Arylalkylamine‐Based Substrates
Author(s) -
Yraola Francesc,
Zorzano Antonio,
Albericio Fernando,
Royo Miriam
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800393
Subject(s) - chemistry , amine oxidase , substrate (aquarium) , methylene , steric effects , amine gas treating , monoamine oxidase , biochemistry , ligand (biochemistry) , stereochemistry , enzyme , organic chemistry , biology , receptor , ecology
SSAO/VAP‐1 substrates may be valuable for the treatment or prevention of diabetes mellitus, as they show insulin‐mimetic properties. This review highlights the importance of studying the relevant steric and electronic features in the development of new ligands with better SSAO/VAP‐1 recognition, enhanced selectivity over other amine oxidases, and improved metabolic behavior.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).