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

Rzepecka, Justyna and Coates, Michelle and Saggar, Moninder and Al-Riyami, Lamyaa and Coltherd, Jennifer and Tay, Hwee Kee and Huggan, Judith and Janicova, Lucia and Khalaf, Abedawn and Siebeke, Ivonne and Suckling, Colin and Harnett, Margaret and Harnett, William (2014) Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties. International Journal for Parasitology, 44 (9). pp. 669-674. ISSN 0020-7519

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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.