Identification of Novel D-Aspartate Oxidase Inhibitors by in Silico Screening and Their Functional and Structural Characterization in Vitro

Journal of Medicinal Chemistry
Masumi KataneHiroshi Homma

Abstract

D-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for acidic D-amino acids, including D-aspartate, a potential agonist of the N-methyl-D-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders, such as schizophrenia. Hence, a DDO inhibitor that increases the brain levels of D-aspartate and thereby activates NMDA receptor function is expected to be a useful compound. To search for potent DDO inhibitor(s), a large number of compounds were screened in silico, and several compounds were identified as candidates. They were then characterized and evaluated as novel DDO inhibitors in vitro (e.g., the inhibitor constant value of 5-aminonicotinic acid for human DDO was 3.80 μM). The present results indicate that some of these compounds may serve as lead compounds for the development of a clinically useful DDO inhibitor and as active site probes to elucidate the structure-function relationships of DDO.

References

Mar 1, 1979·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G ArnoldE Holtzman
Jan 23, 1991·Biochimica Et Biophysica Acta·P P Van VeldhovenG P Mannaerts
Sep 12, 1967·Biochimica Et Biophysica Acta·M Dixon, P Kenworthy
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G E Fagg, A Matus
Sep 22, 1998·FEBS Letters·Z LongK Imai
Sep 5, 2002·The Journal of Comparative Neurology·Kurt ZaarH Dariush Fahimi
Feb 6, 2003·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Kimihiko ShibataRyo-hei Yamada
Aug 3, 2004·Journal of Neuroinflammation·Sheng-Zhou WuSteven W Barger
Jun 9, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Kenji HashimotoMasaomi Iyo
Nov 9, 2005·Fertility and Sterility·Gemma D'AnielloAntimo D'Aniello
May 23, 2006·Cell·Aude PanatierStéphane H R Oliet
May 27, 2006·Behavioural Brain Research·Zachary M WeilSolomon H Snyder
Jul 1, 1935·The Biochemical Journal·H A Krebs
Dec 5, 2006·The FEBS Journal·Masumi KataneHiroshi Homma
Dec 13, 2006·Schizophrenia Research·Inna BendikovGalila Agam
Feb 17, 2007·Biochemical and Biophysical Research Communications·Tomoya KawazoeKiyoshi Fukui
Sep 1, 2007·The EMBO Journal·Jumpei SasabeSadakazu Aiso
Oct 24, 2007·Molecular Neurobiology·Herman Wolosker
May 6, 2008·Bioorganic & Medicinal Chemistry Letters·Tim SpareyMary Beth Young
Oct 10, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francesco ErricoAlessandro Usiello
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ran InoueHisashi Mori
Jan 16, 2010·Nature·Christian HennebergerDmitri A Rusakov
Jun 22, 2010·Chemistry & Biodiversity·Masumi Katane, Hiroshi Homma
Feb 24, 2011·The Journal of Biological Chemistry·Liping WangJonathan V Sweedler
Apr 29, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Masumi Katane, Hiroshi Homma
Jul 16, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hiroko OhideRyuichi Konno
Oct 14, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Toru Nishikawa
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jumpei SasabeSadakazu Aiso
Aug 2, 2012·Amino Acids·Francesco ErricoAlessandro Usiello
Aug 7, 2012·Amino Acids·Silvia SacchiGianluca Molla
Aug 9, 2012·Amino Acids·Nobutoshi OtaJonathan V Sweedler

❮ Previous
Next ❯

Citations

Sep 18, 2018·Expert Opinion on Drug Discovery·Bence SzilágyiGyörgy M Keserű
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gianluca MollaLoredano Pollegioni
Jun 20, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Vincenzo PuggioniSilvia Sacchi
Mar 3, 2021·The FEBS Journal·Valentina RabattoniSilvia Sacchi
Jul 13, 2021·Frontiers in Molecular Biosciences·Loredano PollegioniGiulia Murtas
Jul 22, 2021·Journal of Cellular Biochemistry·Masumi KataneHiroshi Homma

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a form of of brain inflammation due to antibodies against NMDA receptors. Discover the latest research on anti-NMDA receptor encephalitis here.