Curtin University Homepage
  • Library
  • FAQ
    • Log in

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Substituted hippurates and hippurate analogs as substrates and inhibitors of peptidylglycine a-hydroxylating monooxygenase (PHM)

    Access Status
    Fulltext not available
    Authors
    Merkler, D.
    Asser, A.
    Baumgart, L.
    Carballo, N.
    Carpenter, S.
    Chew, G.
    Cosner, C.
    Dusi, J.
    Galloway, L.
    Lowe, Andrew
    Lowe, E.
    King, L.
    Kendig, R.
    Kline, P.
    Malka, R.
    Merkler, K.
    McIntyre, N.
    Romero, M.
    Wilcox, B.
    Owen, T.
    Date
    2008
    Collection
    • Curtin Research Publications
    Type
    Journal Article
    Metadata
    Show full item record
    Abstract

    Peptidyl a-hydroxylating monooxygenase (PHM) functions in vivo towards the biosynthesis of a-amidated peptide hormones in mammals and insects. PHM is a potential target for the development of inhibitors as drugs for the treatment of human disease and as insecticides for the management of insect pests. We show here that relatively simple ground state analogs of the PHM substrate hippuric acid (C6H5-CO-NH-CH2-COOH) inhibit the enzyme with Ki values as low as 0.5 µM. Substitution of sulfur atom(s) into the hippuric acid analog increases the affinity of PHM for the inhibitor. Replacement of the acetylglycine moiety, -CO-NH-CH2-COOH with an S-(thioacetyl)thioglycolic acid moiety, -CS-S-CH2-COOH, yields compounds with the highest PHM affinity. Both S-(2-phenylthioacetyl)thioglycolate and S-(4-ethylthiobenzoyl)thioglycolic acid inhibit the proliferation of cultured human prostate cancer cells at concentrations >100-fold excess of their respective Ki values. Comparison of Ki values between mammalian PHM and insect PHM shows differences in potency suggesting that a PHM-based insecticide with limited human toxicity can be developed. © 2008 Elsevier Ltd. All rights reserved.

    Citation
    Merkler, D. and Asser, A. and Baumgart, L. and Carballo, N. and Carpenter, S. and Chew, G. and Cosner, C. et al. 2008. Substituted hippurates and hippurate analogs as substrates and inhibitors of peptidylglycine a-hydroxylating monooxygenase (PHM). Bioorganic & Medicinal Chemistry. 16 (23): pp. 10061-10074.
    Source Title
    Bioorganic & Medicinal Chemistry
    URI
    http://hdl.handle.net/20.500.11937/5590
    DOI
    10.1016/j.bmc.2008.10.013
    Department
    Nanochemistry Research Institute

    Related items

    Showing items related by title, author, creator and subject.

    • Degradation of e-glass fibre in selected organic acids
      Zahir, Aishath Zehereen (2008)
      E-glass has been widely used as a reinforcing material for years, especially as a plastic reinforcer in the production of GRP (Glass Reinforced Plastic). Failure of GRP materials under stress came in to the picture quite ...
    • Studies of the saturate and aromatic hydrocarbon unresolved complex mixtures in petroleum
      Warton, Benjamin (1999)
      This thesis reports the results of investigations carried out into the composition of the saturate and aromatic unresolved complex mixtures (UCMs) in crude oils. It is divided into two sections. Section A reports on studies ...
    • Effect of sulfuric acid on the pyrolysis of Douglas fir and hybrid poplar wood: Py-GC/MS and TG studies
      Zhou, S.; Wang, Z.; Liaw, S.; Li, Chun-Zhu; Garcia-Perez, M. (2013)
      This paper reports results on the effect of sulfuric acid addition on the pyrolysis of raw and acid washed Douglas fir wood (DFW) (a softwood) and hybrid poplar wood (HPW) (a hardwood). Nitric acid (0.1%) was used to ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorsTitlesSubjectsDocument TypesThis CollectionIssue DateAuthorsTitlesSubjectsDocument Types

    My Account

    Log in

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Connect with Curtin

    • 
    • 
    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Send FeedbackContact Us
    DSpace software copyright © 2002-2015  DuraSpace