Synthesis of a Trimeric gp120 Epitope Mimic Conjugated to a T-Helper Peptide To Improve Antigenicity

• Published in: Journal of the American Chemical Society Vol. 133; no. 10; pp. 3230 - 3233
• Main Authors: Schellinger, Joan G, Danan-Leon, Lieza M, Hoch, Jessica A, Kassa, Aemro, Srivastava, Indresh, Davis, David, Gervay-Hague, Jacquelyn
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.03.2011; Amer Chemical Soc
• Subjects: Amino Acid Sequence; Chemistry; Chemistry, Multidisciplinary; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; HIV Envelope Protein gp120 - chemical synthesis; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HLA-DR Antigens - chemistry; HLA-DR Antigens - immunology; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - immunology; Malaria Vaccines - chemistry; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - chemistry; Peptides - immunology; Physical Sciences; Science & Technology; T-Lymphocytes, Helper-Inducer - immunology; AZIDE-ALKYNE CYCLOADDITION; 1,3-DIPOLAR CYCLOADDITIONS; CLICK CHEMISTRY; IMMUNODEFICIENCY-VIRUS TYPE-1; SOLID-PHASE; PHAGE DISPLAY; HIV-1 PROTEASE; HUMAN MONOCLONAL-ANTIBODIES; IDENTIFICATION; IN-SITU
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja1083915

A fully synthetic trivalent mimotope of gp120 conjugated to pan allelic HLA DR binding epitope was prepared using solid-phase peptide synthesis and optimized copper-catalyzed azide−alkyne cycloaddition. The methodology efficiently provides chemically uniform heteromultimeric peptide constructs with enhanced binding, avidity, and specificity toward an established HIV-neutralizing human antibody, MAb b12. The versatile synthetic strategy serves as a powerful platform for the development of synthetic peptides as potential HIV-1 vaccine candidates.