Anti-Le a monoclonal antibody SPM 522 recognizes an extended Le a epitope

Insights into the differential binding characteristics of anti-Le and anti-Le Le monoclonal antibodies (mAbs) provide information to develop Le Le -based cancer immunotherapeutics while avoiding anti-Le autoimmune reactions. We characterized the epitope recognized by anti-Le mAb SPM 522. We synthesi...

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Published inBioorganic & medicinal chemistry Vol. 56; p. 116628
Main Authors Jegatheeswaran, Sinthuja, Guillemineau, Mickael, Giovane, Richard, Borrillo, Louis, Liao, Liang, Kuir, Deng, Auzanneau, France-Isabelle
Format Journal Article
LanguageEnglish
Published England 15.02.2022
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Summary:Insights into the differential binding characteristics of anti-Le and anti-Le Le monoclonal antibodies (mAbs) provide information to develop Le Le -based cancer immunotherapeutics while avoiding anti-Le autoimmune reactions. We characterized the epitope recognized by anti-Le mAb SPM 522. We synthesized the Le 6-aminohexyl glycoside and report experimental evidence of a minor conformation in solution. The Le and three other 6-aminohexyl glycosides were conjugated to BSA and titration experiments with SPM 522 show that: 1. SPM 522 binds to Le Le better than to Le ; 2. the non-reducing Le galactosyl residue is essential to binding. Competitive ELISA experiments using a panel of tri- to pentasaccharide fragments of Le Le as well as Le analogues indicate that: 1. the Le β-d-galactosyl α hydrophobic patch is crucial to binding; 2. the Le fucosyl residue contributes to binding; 3. the Le d-galactosyl residue also contributes to binding. These results indicate that anti-Le mAb SPM 522 recognizes the Le [1,3]-β-d-Gal tetrasaccharide. We propose that a major recognition element is the extended hydrophobic surface defined by the Le -β-d-Gal residue extending to the α faces of the β-d-GlcNAc and β-d-Gal residues.
ISSN:1464-3391
DOI:10.1016/j.bmc.2022.116628