Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Horiya, Satoru, Bailey, Jennifer K., Temme, J. Sebastian, Guillen Schlippe, Yollete V., Krauss, Isaac J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
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
_version_ 1782313952471941120
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
work_keys_str_mv AT horiyasatoru directedevolutionofmultivalentglycopeptidestightlyrecognizedbyhivantibody2g12
AT baileyjenniferk directedevolutionofmultivalentglycopeptidestightlyrecognizedbyhivantibody2g12
AT temmejsebastian directedevolutionofmultivalentglycopeptidestightlyrecognizedbyhivantibody2g12
AT guillenschlippeyolletev directedevolutionofmultivalentglycopeptidestightlyrecognizedbyhivantibody2g12
AT kraussisaacj directedevolutionofmultivalentglycopeptidestightlyrecognizedbyhivantibody2g12