title: Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties.
abstract: ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, exhibits anti-inflammatory 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 eosinophil 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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Justyna
authors.initials: J
authors.lastname: Rzepecka
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Coates
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Moninder
authors.initials: M
authors.lastname: Saggar
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Lamyaa
authors.initials: L
authors.lastname: Al-Riyami
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Coltherd
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
authors.forename: Hwee Kee
authors.initials: HK
authors.lastname: Tay
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK.
authors.forename: Judith K
authors.initials: JK
authors.lastname: Huggan
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Lucia
authors.initials: L
authors.lastname: Janicova
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK.
authors.forename: Abedawn I
authors.initials: AI
authors.lastname: Khalaf
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Siebeke
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Harnett
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland, UK. Electronic address: w.harnett@strath.ac.uk.
authors.forename: William
authors.initials: W
authors.lastname: Harnett
mesh_terms: D063486:Acanthocheilonema / Q000378:metabolism*; D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D007155:Immunologic Factors; D010047:Ovalbumin
keywords: Asthma; ES-62; Immunomodulation; Parasitic helminth; Phosphorylcholine