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Understanding the Recognition of Lewis X by Anti-Lex Monoclonal Antibodies

Show simple item record Moore, Christopher Auzanneau, France-Isabelle 2015-12-02T13:50:03Z 2015-12-02T13:50:03Z 2013-09-23
dc.identifier.issn 0022-2623
dc.description.abstract The recognition of the Lex antigen by the anti-Lex monoclonal antibody (mAb) SH1 was studied by ELISA using a panel of 4”-modified Lex analogues. We confirmed that these analogues maintained the stacked conformation adopted by natural Lex antigen using 1D ROESY experiments and measuring intramolecular distances. Our binding studies show that the 4-OH” of galactose behaves as an H-bond donor to an electronegative amino acid side chain in the SH1 binding site. While removal of this H-bond leads to reduced inhibition, disturbing the hydrophobic α face of the β-galactosyl residue leads to complete loss of binding to SH1. We compared our results to the crystal structure of the Fab fragment of anti-Lex mAb 291-2G3-A complexed with Lex (PDB entry code 1UZ8). While no H-bond involving the 4-OH” was described hydrophobic interactions between a tryptophan residue and the β-galactoside α face are observed. We conclude that the hydrophobic α face that is uniquely displayed by β-galactosyl residues is essential to the recognition of the Lex antigen by anti-Lex antibodies. en_US
dc.description.sponsorship Natural Sciences and Engineering Research Council of Canada en_US
dc.publisher American Chemical Society en_US
dc.subject Tumor Associated Carbohydrate en_US
dc.subject ROESY en_US
dc.subject ELISA en_US
dc.subject H bond en_US
dc.subject Hydrophobic patch en_US
dc.title Understanding the Recognition of Lewis X by Anti-Lex Monoclonal Antibodies en_US
dc.type Article en_US
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dcterms.relation J. Med. Chem. 2013, 56, 8183?8190

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