Design of a novel LOX-1 receptor antagonist mimicking the natural substrate

Mattia Falconi, Sarah Ciccone, Paola D'Arrigo, Fiorenza Viani, Roberto Sorge, Giuseppe Novelli, Patrizia Patrizi, Alessandro Desideri, Silvia Biocca

Research output: Contribution to journalArticle

Abstract

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the major receptor for oxidized low-density lipoprotein (ox-LDL) in endothelial cells, is overexpressed in atherosclerotic lesions. LOX-1 specific inhibitors, urgently necessary to reduce the rate of atherosclerotic and inflammation processes, are not yet available. We have designed and synthesized a new modified oxidized phospholipid, named PLAzPC, which plays to small scale the ligand-receptor recognition scheme. Molecular docking simulations confirm that PLAzPC disables the hydrophobic component of the ox-LDL recognition domain and allows the interaction of the l-lysine backbone charged groups with the solvent and with the charged/polar residues located around the edges of the LOX-1 hydrophobic tunnel. Binding assays, in a cell model system expressing human LOX-1 receptors, confirm that PLAzPC markedly inhibits ox-LDL binding to LOX-1 with higher efficacy compared to previously identified inhibitors.

Original languageEnglish
Pages (from-to)340-345
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume438
Issue number2
DOIs
Publication statusPublished - Aug 23 2013

Keywords

  • Atherosclerosis
  • Cell-based assay
  • LOX-1 inhibitor
  • Molecular docking
  • Ox-LDL
  • Oxidized phospholipids

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Falconi, M., Ciccone, S., D'Arrigo, P., Viani, F., Sorge, R., Novelli, G., Patrizi, P., Desideri, A., & Biocca, S. (2013). Design of a novel LOX-1 receptor antagonist mimicking the natural substrate. Biochemical and Biophysical Research Communications, 438(2), 340-345. https://doi.org/10.1016/j.bbrc.2013.07.073