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Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12
[Image: see text] 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 librarie...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004241/ https://www.ncbi.nlm.nih.gov/pubmed/24645849 http://dx.doi.org/10.1021/ja500678v |
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author | Horiya, Satoru Bailey, Jennifer K. Temme, J. Sebastian Guillen Schlippe, Yollete V. Krauss, Isaac J. |
author_facet | Horiya, Satoru Bailey, Jennifer K. Temme, J. Sebastian Guillen Schlippe, Yollete V. Krauss, Isaac J. |
author_sort | Horiya, Satoru |
collection | PubMed |
description | [Image: see text] 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 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. |
format | Online Article Text |
id | pubmed-4004241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-40042412015-03-19 Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12 Horiya, Satoru Bailey, Jennifer K. Temme, J. Sebastian Guillen Schlippe, Yollete V. Krauss, Isaac J. J Am Chem Soc [Image: see text] 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 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. American Chemical Society 2014-03-19 2014-04-09 /pmc/articles/PMC4004241/ /pubmed/24645849 http://dx.doi.org/10.1021/ja500678v Text en Copyright © 2014 American Chemical Society |
spellingShingle | Horiya, Satoru Bailey, Jennifer K. Temme, J. Sebastian Guillen Schlippe, Yollete V. Krauss, Isaac J. Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12 |
title | Directed
Evolution of Multivalent Glycopeptides Tightly
Recognized by HIV Antibody 2G12 |
title_full | Directed
Evolution of Multivalent Glycopeptides Tightly
Recognized by HIV Antibody 2G12 |
title_fullStr | Directed
Evolution of Multivalent Glycopeptides Tightly
Recognized by HIV Antibody 2G12 |
title_full_unstemmed | Directed
Evolution of Multivalent Glycopeptides Tightly
Recognized by HIV Antibody 2G12 |
title_short | Directed
Evolution of Multivalent Glycopeptides Tightly
Recognized by HIV Antibody 2G12 |
title_sort | directed
evolution of multivalent glycopeptides tightly
recognized by hiv antibody 2g12 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004241/ https://www.ncbi.nlm.nih.gov/pubmed/24645849 http://dx.doi.org/10.1021/ja500678v |
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