A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry

Karen Maria Alt, Brett M Paterson, Erik Westein, Stacey Rudd, Stan Poniger, Schweta Jagdale, Katie Ardipradja, Timothy U Connell, Guy Yeoman Krippner, Ashish Kumar Narayan Nair, Xiaowei Wang, Henri Tochon-Danguy, Paul Stephen Donnelly, Karlheinz Peter, Christoph Eugen Hagemeyer

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules. A two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for site-specific incorporation of strained cyclooctyne functional groups into antibodies. The second step of this modular approach involves the copper-free azide-alkyne cycloaddition click reaction.
Original languageEnglish
Pages (from-to)7515 - 7519
Number of pages5
JournalAngewandte Chemie - International Edition
Volume54
Issue number26
DOIs
Publication statusPublished - 2015
Externally publishedYes

Cite this

Alt, Karen Maria ; Paterson, Brett M ; Westein, Erik ; Rudd, Stacey ; Poniger, Stan ; Jagdale, Schweta ; Ardipradja, Katie ; Connell, Timothy U ; Krippner, Guy Yeoman ; Nair, Ashish Kumar Narayan ; Wang, Xiaowei ; Tochon-Danguy, Henri ; Donnelly, Paul Stephen ; Peter, Karlheinz ; Hagemeyer, Christoph Eugen. / A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry. In: Angewandte Chemie - International Edition. 2015 ; Vol. 54, No. 26. pp. 7515 - 7519.
@article{5b7b5bf1ba5a45de804e9bb314d7c0b1,
title = "A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry",
abstract = "A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules. A two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for site-specific incorporation of strained cyclooctyne functional groups into antibodies. The second step of this modular approach involves the copper-free azide-alkyne cycloaddition click reaction.",
author = "Alt, {Karen Maria} and Paterson, {Brett M} and Erik Westein and Stacey Rudd and Stan Poniger and Schweta Jagdale and Katie Ardipradja and Connell, {Timothy U} and Krippner, {Guy Yeoman} and Nair, {Ashish Kumar Narayan} and Xiaowei Wang and Henri Tochon-Danguy and Donnelly, {Paul Stephen} and Karlheinz Peter and Hagemeyer, {Christoph Eugen}",
year = "2015",
doi = "10.1002/anie.201411507",
language = "English",
volume = "54",
pages = "7515 -- 7519",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "Wiley-Blackwell",
number = "26",

}

A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry. / Alt, Karen Maria; Paterson, Brett M; Westein, Erik; Rudd, Stacey; Poniger, Stan; Jagdale, Schweta; Ardipradja, Katie; Connell, Timothy U; Krippner, Guy Yeoman; Nair, Ashish Kumar Narayan; Wang, Xiaowei; Tochon-Danguy, Henri; Donnelly, Paul Stephen; Peter, Karlheinz; Hagemeyer, Christoph Eugen.

In: Angewandte Chemie - International Edition, Vol. 54, No. 26, 2015, p. 7515 - 7519.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry

AU - Alt, Karen Maria

AU - Paterson, Brett M

AU - Westein, Erik

AU - Rudd, Stacey

AU - Poniger, Stan

AU - Jagdale, Schweta

AU - Ardipradja, Katie

AU - Connell, Timothy U

AU - Krippner, Guy Yeoman

AU - Nair, Ashish Kumar Narayan

AU - Wang, Xiaowei

AU - Tochon-Danguy, Henri

AU - Donnelly, Paul Stephen

AU - Peter, Karlheinz

AU - Hagemeyer, Christoph Eugen

PY - 2015

Y1 - 2015

N2 - A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules. A two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for site-specific incorporation of strained cyclooctyne functional groups into antibodies. The second step of this modular approach involves the copper-free azide-alkyne cycloaddition click reaction.

AB - A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules. A two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for site-specific incorporation of strained cyclooctyne functional groups into antibodies. The second step of this modular approach involves the copper-free azide-alkyne cycloaddition click reaction.

UR - http://onlinelibrary.wiley.com/doi/10.1002/anie.201411507/abstract

U2 - 10.1002/anie.201411507

DO - 10.1002/anie.201411507

M3 - Article

VL - 54

SP - 7515

EP - 7519

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

SN - 1433-7851

IS - 26

ER -