1279115-34-2Relevant academic research and scientific papers
Novel hydrazine molecules as tools to understand the flexibility of vascular adhesion protein-1 ligand-binding site: Toward more selective inhibitors
Nurminen, Elisa M.,Pihlavisto, Marjo,Lázár, László,Pentik?inen, Ulla,Fül?p, Ferenc,Pentik?inen, Olli T.
experimental part, p. 2143 - 2154 (2011/05/30)
Vascular adhesion protein-1 (VAP-1) belongs to a family of amine oxidases. It plays a role in leukocyte trafficking and in amine compound metabolism. VAP-1 is linked to various diseases, such as Alzheimer's disease, psoriasis, depression, diabetes, and obesity. Accordingly, selective inhibitors of VAP-1 could potentially be used to treat those diseases. In this study, eight novel VAP-1 hydrazine derivatives were synthesized and their VAP-1 and monoamine oxidase (MAO) inhibition ability was determined in vitro. MD simulations of VAP-1 with these new molecules reveal that the VAP-1 ligand-binding pocket is flexible and capable of fitting substantially larger ligands than was previously believed. The increase in the size of the VAP-1 ligands, together with the methylation of the secondary nitrogen atom of the hydrazine moiety, improves the VAP-1 selectivity over MAO.
