Rational design and synthesis of peptide ligands for an anti-Carbohydrate antibody and Their immunochemical characterization

• Published in: Bioorganic & medicinal chemistry 2003-03, Vol.11 (5), p.781-788
• Main Authors: Johnson, Margaret A, Eniade, Adewale A, Pinto, B.Mario
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies - immunology; Bacteriology; Biological and medical sciences; Carbohydrate Sequence; Carbohydrates - immunology; Drug Design; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Immunochemistry; Immunohistochemistry; Lipopolysaccharides - chemistry; Lipopolysaccharides - immunology; Microbiology; Models, Molecular; Molecular Conformation; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - immunology; Shigella flexneri - chemistry; Shigella flexneri - immunology; Thermodynamics; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00449-2

Molecular mimics of carbohydrates present an alternative source of compounds to target pathways involving protein–carbohydrate interactions. Certain peptides act as molecular mimics of carbohydrates in binding to anti-carbohydrate antibodies. A series of potential peptide ligands for the anti-carbohydrate antibody SYA/J6, directed against Shigella flexneri Y, was designed by molecular modeling based on a crystal structure of the antibody complex with a carbohydrate-mimetic peptide. These octapeptides were synthesized using solid-phase peptide synthesis, and their recognition by the antibody was investigated. The results shed light on the nature of peptide–carbohydrate mimicry. The design, synthesis, and immunochemical characterization of a series of peptide mimetics of the Shigella flexneri Y O-polysaccharide are described.