Human Copper-Containing Amine Oxidases in Drug Design and Development

Serhii Vakal, Sirpa Jalkanen, Käthe M. Dahlström, Tiina A. Salminen

Research output: Contribution to journalReview Article or Literature ReviewScientificpeer-review

2 Citations (Scopus)

Abstract

Two members of the copper-containing amine oxidase family are physiologically important proteins: (1) Diamine oxidase (hDAO; AOC1) with a preference for diamines is involved in degradation of histamine and (2) Vascular adhesion protein-1 (hVAP-1; AOC3) with a preference for monoamines is a multifunctional cell-surface receptor and an enzyme. hVAP-1-targeted inhibitors are designed to treat inflammatory diseases and cancer, whereas the off-target binding of the designed inhibitors to hDAO might result in adverse drug reactions. The X-ray structures for both human enzymes are solved and provide the basis for computer-aided inhibitor design, which has been reported by several research groups. Although the putative off-target effect of hDAO is less studied, computational methods could be easily utilized to avoid the binding of VAP-1-targeted inhibitors to hDAO. The choice of the model organism for preclinical testing of hVAP-1 inhibitors is not either trivial due to species-specific binding properties of designed inhibitors and different repertoire of copper-containing amine oxidase family members in mammalian species. Thus, the facts that should be considered in hVAP-1-targeted inhibitor design are discussed in light of the applied structural bioinformatics and structural biology approaches.

Original languageEnglish
Article number1293
JournalMolecules
Volume25
Issue number6
DOIs
Publication statusPublished - 12 Mar 2020
MoE publication typeA2 Review article in a scientific journal

Keywords

  • Amine Oxidase (Copper-Containing)/chemistry
  • Cell Adhesion Molecules/chemistry
  • Drug Design
  • Drug Development/trends
  • Histamine/chemistry
  • Humans

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