Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12

被引:70
作者
Horiya, Satoru [1 ]
Bailey, Jennifer K. [1 ]
Temme, J. Sebastian [1 ]
Schippe, Yollete V. Guillen [2 ,3 ]
Krauss, Isaac J. [1 ]
机构
[1] Brandeis Univ, Dept Chem, Waltham, MA 02454 USA
[2] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO SELECTION; MESSENGER-RNA DISPLAY; VACCINE DESIGN; DC-SIGN; OLIGOMANNOSE CLUSTERS; CARBOHYDRATE EPITOPE; PURIFIED COMPONENTS; RIBOSOMAL SYNTHESIS; UNNATURAL PEPTIDES;
D O I
10.1021/ja500678v
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 similar to 10(13) glycopeptides containing multiple Man(9) 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.
引用
收藏
页码:5407 / 5415
页数:9
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