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Human copper-containing amine oxidases in drug design and development

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

Human copper-containing amine oxidases in drug design and development

Tiina A. Salminen
Käthe M. Dahlström
Sirpa Jalkanen
Serhii Vakal
Katso/Avaa
Publisher's PDF (13.86Mb)
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MDPI AG
doi:10.3390/molecules25061293
URI
https://www.mdpi.com/1420-3049/25/6/1293
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042821439
Tiivistelmä

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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