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Synthetic Phenolic Glycolipids for Application in Diagnostic Tests for Leprosy
Authors:J. Hessel M. van Dijk  Anouk van Hooij  L. Melanie Groot  Jolijn Geboers  Rosita Moretti  Els Verhard-Seymonsbergen  Danielle de Jong  Gijs A. van der Marel  Paul L. A. M. Corstjens  Prof. Jeroen D. C. Codée  Annemieke Geluk
Affiliation:1. Leiden Institute for Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands

These authors contributed equally to this work.;2. Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden (The, Netherlands

These authors contributed equally to this work.;3. Leiden Institute for Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands;4. Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden (The, Netherlands;5. Department Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden (The, Netherlands

Abstract:Point-of-care (POC) diagnostic tests for the rapid detection of individuals infected with Mycobacterium leprae, the causative pathogen of leprosy, represent efficient tools to guide therapeutic and prophylactic treatment strategies in leprosy control programs, thus positively contributing to clinical outcome and reducing transmission of this infectious disease. Levels of antibodies directed against the M. leprae-specific phenolic glycolipid I (PGL−I) closely correlate with an individual's bacterial load and a higher risk of developing leprosy. We describe herein the assembly of a set of PGL glycans carrying the characteristic phenol aglycon and featuring different methylation patterns. The PGL trisaccharides were applied to construct neoglycoproteins that were used to detect anti-PGL IgM antibodies in leprosy patients. ELISAs and quantitative lateral-flow assays based on up-converting nanoparticles (UCP-LFAs) showed that the generated PGL−I and PGL-II trisaccharide neoglycoconjugates can be applied for the detection of anti M. leprae IgM antibodies in POC tests.
Keywords:carbohydrates  diagnosis  glycoconjugates  lateral flow assay  leprosy
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