Directed evolution of multivalent glycopeptides tightly recognized by HIV antibody 2G12.

Directed evolution of multivalent glycopeptides tightly recognized by HIV antibody 2G12.
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DOI:
10.1021/ja500678v
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发表时间:
2014-04-09
影响因子:
15
通讯作者:
Krauss IJ
Krauss IJ
中科院分区:
化学1区
文献类型:
--
作者:
Horiya S;Bailey JK;Temme JS;Guillen Schlippe YV;Krauss IJ

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在此,我们报告了一种方法,在体外选择的多价糖肽,结合mRNA显示与掺入非天然氨基酸和“点击”化学。我们已经证明了使用这种方法来设计潜在的抗HIV的糖肽疫苗。从含有多种Man 9聚糖的MAN 1013糖肽文库中,我们选择了以皮摩尔至低纳摩尔亲和力结合HIV广泛中和抗体2G 12的变体。这与天然2G 12-gp 120相互作用的强度相当,并且是迄今为止用含有3-5个聚糖的构建体实现的最强亲和力。因此,这些糖肽在HIV疫苗设计中具有很大的意义。
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 ∼1013 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.
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