Novel hydrazine molecules as tools to understand the flexibility of vascular adhesion protein-1 ligand-binding site

Toward more selective inhibitors

Elisa M. Nurminen, Marjo Pihlavisto, L. Lázár, Ulla Pentikäinen, F. Fülöp, Olli T. Pentikäinen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2143-2154
Number of pages12
JournalJournal of Medicinal Chemistry
Volume54
Issue number7
DOIs
Publication statusPublished - Apr 14 2011

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hydrazine
Blood Vessels
Binding Sites
Ligands
Proteins
Monoamine Oxidase
Amines
Aptitude

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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, L.; Pentikäinen, Ulla; Fülöp, F.; Pentikäinen, Olli T.

In: Journal of Medicinal Chemistry, Vol. 54, No. 7, 14.04.2011, p. 2143-2154.

Research output: Contribution to journalArticle

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