Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties

Justyna Rzepecka, Michelle Coates, Moninder Saggar, Lamyaa Al-Riyami, Jennifer Coltherd, Hwee Kee Tay, Judith Huggan, Lucia Janicova, Abedawn Khalaf, Ivonne Siebeke, Colin Suckling, Margaret Harnett, William Harnett

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Abstract

ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, exhibits anti-inflamma-tory properties by virtue of covalently attached phosphorylcholine moieties. Screening of a library of ES-62 phosphorylcholine-based small molecule analogues (SMAs) revealed that two compounds, termed 11a and 12b, mirrored the helminth product both in inhibiting mast cell degranulation and cytokine responses in vitro and in preventing ovalbumin-induced Th2-associated airway inflammation and eosin- ophil infiltration of the lungs in mice. Furthermore, the two SMAs inhibited neutrophil infiltration of the
lungs when administered therapeutically. ES-62-SMAs 11a and 12b thus represent starting points for novel drug development for allergies such as asthma.
Original languageEnglish
Pages (from-to)669-674
Number of pages6
JournalInternational Journal for Parasitology
Volume44
Issue number9
Early online date12 Jun 2014
DOIs
Publication statusPublished - Aug 2014

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Keywords

  • asthma
  • ES-62
  • parasitic helminth
  • immunomodulation
  • phosphorylcholine
  • Acanthocheilonema viteae

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