Genetically-encoded fragment-based discovery (GE-FBD) of glycopeptide ligands with differential selectivity for antibodies related to mycobacterial infections. Issue 2 (19th December 2017)

• Record Type: Journal Article
• Authors: Chou, Ying; Kitova, Elena N.; Joe, Maju; Brunton, Richard; Lowary, Todd L.; Klassen, John S.; Derda, Ratmir
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 2(2017)
• Page Start: 223
• Page End: 227
• Publication Date: 2017-12-19
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02783d
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : GE-FBD discovered discriminatory antigens for antibodies (Abs) associated with Mycobacterial infections; the accurate detection of such Abs is critical for global management of tuberculosis. 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 10 8 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.