A2 Refereed review article in a scientific journal

Human copper-containing amine oxidases in drug design and development




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

PublisherMDPI AG

Publication year2020

JournalMolecules

Journal name in sourceMolecules

Volume25

Issue6

Number of pages29

ISSN1420-3049

eISSN1420-3049

DOIhttps://doi.org/10.3390/molecules25061293

Web address https://www.mdpi.com/1420-3049/25/6/1293

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/46859756


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.


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