Flexible antibodies with nonprotein hinges

There is a significant need for antibodies that can bind targets with greater affinity. Here we describe a novel strategy employing chemical semisynthesis to produce symmetroadhesins: antibody-like molecules having nonprotein hinge regions that are more flexible and extendible and are capable of two...

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Main Authors:	CAPON, Daniel J., KANEKO, Naoki, YOSHIMORI, Takayuki, SHIMADA, Takashi, WURM, Florian M., HWANG, Peter K., TONG, Xiaohe, ADAMS, Staci A., SIMMONS, Graham, SATO, Taka-Aki, TANAKA, Koichi
Format:	Online
Language:	English
Published:	The Japan Academy 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309923/

id	pubmed-3309923
recordtype	oai_dc
spelling	pubmed-33099232012-04-20 Flexible antibodies with nonprotein hinges CAPON, Daniel J. KANEKO, Naoki YOSHIMORI, Takayuki SHIMADA, Takashi WURM, Florian M. HWANG, Peter K. TONG, Xiaohe ADAMS, Staci A. SIMMONS, Graham SATO, Taka-Aki TANAKA, Koichi Original Article There is a significant need for antibodies that can bind targets with greater affinity. Here we describe a novel strategy employing chemical semisynthesis to produce symmetroadhesins: antibody-like molecules having nonprotein hinge regions that are more flexible and extendible and are capable of two-handed binding. Native chemical ligation was carried out under mild, non-denaturing conditions to join a ligand binding domain (Aβ peptide) to an IgG1 Fc dimer via discrete oxyethylene oligomers of various lengths. Two-handed Aβ–Fc fusion proteins were obtained in quantitative yield and shown by surface plasmon resonance to bind an anti-Aβ antibody with a KD at least two orders of magnitude greater than the cognate Aβ peptide. MALDI-TOF MS analysis confirmed the protein/nonprotein/protein structure of the two-handed molecules, demonstrating its power to characterize complex protein-nonprotein hybrids by virtue of desorption/ionization mediated by peptide sequences contained therein. We anticipate many applications for symmetroadhesins that combine the target specificity of antibodies with the novel physical, chemical and biological properties of nonprotein hinges. The Japan Academy 2011-11-11 /pmc/articles/PMC3309923/ /pubmed/22075761 http://dx.doi.org/10.2183/pjab.87.603 Text en © 2011 The Japan Academy This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	CAPON, Daniel J. KANEKO, Naoki YOSHIMORI, Takayuki SHIMADA, Takashi WURM, Florian M. HWANG, Peter K. TONG, Xiaohe ADAMS, Staci A. SIMMONS, Graham SATO, Taka-Aki TANAKA, Koichi
spellingShingle	CAPON, Daniel J. KANEKO, Naoki YOSHIMORI, Takayuki SHIMADA, Takashi WURM, Florian M. HWANG, Peter K. TONG, Xiaohe ADAMS, Staci A. SIMMONS, Graham SATO, Taka-Aki TANAKA, Koichi Flexible antibodies with nonprotein hinges
author_facet	CAPON, Daniel J. KANEKO, Naoki YOSHIMORI, Takayuki SHIMADA, Takashi WURM, Florian M. HWANG, Peter K. TONG, Xiaohe ADAMS, Staci A. SIMMONS, Graham SATO, Taka-Aki TANAKA, Koichi
author_sort	CAPON, Daniel J.
title	Flexible antibodies with nonprotein hinges
title_short	Flexible antibodies with nonprotein hinges
title_full	Flexible antibodies with nonprotein hinges
title_fullStr	Flexible antibodies with nonprotein hinges
title_full_unstemmed	Flexible antibodies with nonprotein hinges
title_sort	flexible antibodies with nonprotein hinges
description	There is a significant need for antibodies that can bind targets with greater affinity. Here we describe a novel strategy employing chemical semisynthesis to produce symmetroadhesins: antibody-like molecules having nonprotein hinge regions that are more flexible and extendible and are capable of two-handed binding. Native chemical ligation was carried out under mild, non-denaturing conditions to join a ligand binding domain (Aβ peptide) to an IgG1 Fc dimer via discrete oxyethylene oligomers of various lengths. Two-handed Aβ–Fc fusion proteins were obtained in quantitative yield and shown by surface plasmon resonance to bind an anti-Aβ antibody with a KD at least two orders of magnitude greater than the cognate Aβ peptide. MALDI-TOF MS analysis confirmed the protein/nonprotein/protein structure of the two-handed molecules, demonstrating its power to characterize complex protein-nonprotein hybrids by virtue of desorption/ionization mediated by peptide sequences contained therein. We anticipate many applications for symmetroadhesins that combine the target specificity of antibodies with the novel physical, chemical and biological properties of nonprotein hinges.
publisher	The Japan Academy
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309923/
_version_	1611516000242499584

Flexible antibodies with nonprotein hinges

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