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Issue 2, 2018
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Genetically-encoded fragment-based discovery (GE-FBD) of glycopeptide ligands with differential selectivity for antibodies related to mycobacterial infections

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Abstract

Accurate identification of tuberculosis (TB), caused by Mycobacterium tuberculosis, is important for global disease management. Point-of-care serological tests may improve TB diagnosis; however, specificities of available serodiagnostics are sub-optimal. We employed genetically encoded fragment-based discovery (GE-FBD) to select ligands for antibodies directed against the mycobacterial cell wall component lipoarabinomannan (LAM), a potent antigen. GE-FBD employed a phage displayed library of 108 heptapeptides, chemically modified with an arabinofuranosyl hexasaccharide fragment of LAM (Ara6), and the anti-LAM antibody CS-35 as a bait. The selection gave rise to glycopeptides with an enhanced affinity and selectivity for CS-35 but not for 906.4321 antibody, both of which bind to Ara6 with a comparable affinity. Multivalent assays incorporating the discovered ligands Ara6-ANSSFAP, Ara6-DAHATLR and Ara6-TTYVVNP exhibited up to 19-fold discrimination between CS-35 and 906.4321. The use of the Ara6 antigen alone failed to distinguish these antibodies. Thus, GE-FBD gives rise to ligands that differentiate monoclonal antibodies with enhanced specificity. This technology could facilitate the development of effective point-of-care serological tests for mycobacterial and other infections.

Graphical abstract: Genetically-encoded fragment-based discovery (GE-FBD) of glycopeptide ligands with differential selectivity for antibodies related to mycobacterial infections

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Publication details

The article was received on 14 Nov 2017, accepted on 08 Dec 2017 and first published on 19 Dec 2017


Article type: Paper
DOI: 10.1039/C7OB02783D
Citation: Org. Biomol. Chem., 2018,16, 223-227
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    Genetically-encoded fragment-based discovery (GE-FBD) of glycopeptide ligands with differential selectivity for antibodies related to mycobacterial infections

    Y. Chou, E. N. Kitova, M. Joe, R. Brunton, T. L. Lowary, J. S. Klassen and R. Derda, Org. Biomol. Chem., 2018, 16, 223
    DOI: 10.1039/C7OB02783D

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