title: Directed evolution of multivalent glycopeptides tightly recognized by HIV antibody 2G12.
abstract: Herein, we report a method for in vitro selection of multivalent glycopeptides, combining mRNA display with incorporation of unnatural amino acids and "click" chemistry. We have demonstrated the use of this method to design potential glycopeptide vaccines against HIV. From libraries of ~10(13) glycopeptides containing multiple Man9 glycan(s), we selected variants that bind to HIV broadly neutralizing antibody 2G12 with picomolar to low nanomolar affinity. This is comparable to the strength of the natural 2G12-gp120 interaction, and is the strongest affinity achieved to date with constructs containing 3-5 glycans. These glycopeptides are therefore of great interest in HIV vaccine design.
authors.affiliation: Department of Chemistry, Brandeis University , Waltham, Massachusetts 02454-9110, United States.
authors.forename: Satoru
authors.initials: S
authors.lastname: Horiya
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Bailey
authors.forename: J Sebastian
authors.initials: JS
authors.lastname: Temme
authors.forename: Yollete V
authors.initials: YV
authors.lastname: Guillen Schlippe
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Krauss
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D057930:Click Chemistry; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology; D015394:Molecular Structure
chemical_list: D016915:AIDS Vaccines; D006020:Glycopeptides; D015483:HIV Antibodies