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Naphthalenes as inhibitors of myeloperoxidase: Direct and indirect mechanisms of inhibition

  • Inflammation and Immunomodulation
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Abstract

Control of myeloperoxidase (MPO) may be an important consideration in disorders where excessive PMN elastase activity is a significant factor. There are, however, two mechanisms for the apparent regulation of MPO: i) inhibit the enzyme directly, and ii) prevent the ensuing HOCl induced oxidation by using a surrogate reducing agent. Appropriate methodology has been devised to distinguish true MPO inhibitors. With the exception of NaN3, many MPO inhibitors fall into the latter category and do not actually regulate the enzyme. Several potent organic inhibitors have been discovered, which, because of their structural selectivity, appear to associate specifically with a binding site on the enzyme, rather than attaching indiscriminately to a hydrophobic domain. By controlling the enzyme, these compounds protect α-1-PI from MPO induced damage, and could serve better than antioxidants to define the role of MPO in elastase induced injury.

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Abbreviations

α-1-PI:

α-1-proteinase inhibitor

BW755C:

3-amino-1-[m-(fluoromethyl)-phenyl]-2-pyrazolize

CTAB:

cetyltrimethyl ammonium bromide

HLE:

human leukocyte elastase

MPO:

myeloperoxidase

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Author notes

  1. R. W. Egan

    Present address: Schering-Plough Research, 60 Orange Street, 07003, Bloomfield, NJ, USA

Authors and Affiliations

  1. Merck Sharp and Dohme Research Laboratories, 07065, Rahway, New Jersey, USA

    R. W. Egan, W. K. Hagmann & P. H. Gale

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Egan, R.W., Hagmann, W.K. & Gale, P.H. Naphthalenes as inhibitors of myeloperoxidase: Direct and indirect mechanisms of inhibition. Agents and Actions 29, 266–276 (1990). https://doi.org/10.1007/BF01966457

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