A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies

Mathias B Bertelsen; Emily Tsang; Johan Palmfeldt; Celine Hurup Kristoffersen; Marija Nisavic; Kurt V Gothelf

doi:10.1021/acs.bioconjchem.4c00317

A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies

Mathias B Bertelsen, Emily Tsang, Johan Palmfeldt, Celine Hurup Kristoffersen, Marija Nisavic, Kurt V Gothelf^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Arginine is one of the less commonly targeted amino acids in protein bioconjugation, despite its unique reactivity and abundance on the surface of proteins. In this work, a molecule containing diketopinic acid and an azide handle was developed for the chemo-selective bioconjugation to arginine. This compound proved to be efficient for bioconjugation to IgG1 and IgG4 antibodies, achieving mono- and double-label conversion rates of 37-44 and 12-30%, respectively. Mass spectrometry analysis confirmed the antibody modification at two conserved regions. The compound was also applied for the labeling of other proteins such as transferrin, BSA, and an EgA1 nanobody. The conjugation was shown to be reversible using an o-phenylenediamine-based alkaline solution. This novel conjugation method offers precise and stable bioconjugation to proteins, enhancing the potential for various biomedical applications.

Original language	English
Journal	Bioconjugate Chemistry
Volume	35
Issue	11
Pages (from-to)	1755-1761
Number of pages	7
ISSN	1043-1802
DOIs	https://doi.org/10.1021/acs.bioconjchem.4c00317
Publication status	Published - 20 Nov 2024

Access to Document

10.1021/acs.bioconjchem.4c00317

Cite this

@article{28b75af9b11e42239af767fa542b37a1,

title = "A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies",

abstract = "Arginine is one of the less commonly targeted amino acids in protein bioconjugation, despite its unique reactivity and abundance on the surface of proteins. In this work, a molecule containing diketopinic acid and an azide handle was developed for the chemo-selective bioconjugation to arginine. This compound proved to be efficient for bioconjugation to IgG1 and IgG4 antibodies, achieving mono- and double-label conversion rates of 37-44 and 12-30%, respectively. Mass spectrometry analysis confirmed the antibody modification at two conserved regions. The compound was also applied for the labeling of other proteins such as transferrin, BSA, and an EgA1 nanobody. The conjugation was shown to be reversible using an o-phenylenediamine-based alkaline solution. This novel conjugation method offers precise and stable bioconjugation to proteins, enhancing the potential for various biomedical applications.",

author = "Bertelsen, {Mathias B} and Emily Tsang and Johan Palmfeldt and Kristoffersen, {Celine Hurup} and Marija Nisavic and Gothelf, {Kurt V}",

year = "2024",

month = nov,

day = "20",

doi = "10.1021/acs.bioconjchem.4c00317",

language = "English",

volume = "35",

pages = "1755--1761",

journal = "Bioconjugate Chemistry",

issn = "1043-1802",

publisher = "American Chemical Society",

number = "11",

}

A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies. / Bertelsen, Mathias B; Tsang, Emily ; Palmfeldt, Johan et al.
In: Bioconjugate Chemistry, Vol. 35, No. 11, 20.11.2024, p. 1755-1761.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies

AU - Bertelsen, Mathias B

AU - Tsang, Emily

AU - Palmfeldt, Johan

AU - Kristoffersen, Celine Hurup

AU - Nisavic, Marija

AU - Gothelf, Kurt V

PY - 2024/11/20

Y1 - 2024/11/20

N2 - Arginine is one of the less commonly targeted amino acids in protein bioconjugation, despite its unique reactivity and abundance on the surface of proteins. In this work, a molecule containing diketopinic acid and an azide handle was developed for the chemo-selective bioconjugation to arginine. This compound proved to be efficient for bioconjugation to IgG1 and IgG4 antibodies, achieving mono- and double-label conversion rates of 37-44 and 12-30%, respectively. Mass spectrometry analysis confirmed the antibody modification at two conserved regions. The compound was also applied for the labeling of other proteins such as transferrin, BSA, and an EgA1 nanobody. The conjugation was shown to be reversible using an o-phenylenediamine-based alkaline solution. This novel conjugation method offers precise and stable bioconjugation to proteins, enhancing the potential for various biomedical applications.

AB - Arginine is one of the less commonly targeted amino acids in protein bioconjugation, despite its unique reactivity and abundance on the surface of proteins. In this work, a molecule containing diketopinic acid and an azide handle was developed for the chemo-selective bioconjugation to arginine. This compound proved to be efficient for bioconjugation to IgG1 and IgG4 antibodies, achieving mono- and double-label conversion rates of 37-44 and 12-30%, respectively. Mass spectrometry analysis confirmed the antibody modification at two conserved regions. The compound was also applied for the labeling of other proteins such as transferrin, BSA, and an EgA1 nanobody. The conjugation was shown to be reversible using an o-phenylenediamine-based alkaline solution. This novel conjugation method offers precise and stable bioconjugation to proteins, enhancing the potential for various biomedical applications.

UR - http://www.scopus.com/inward/record.url?scp=85206991870&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.4c00317

DO - 10.1021/acs.bioconjchem.4c00317

M3 - Journal article

C2 - 39432883

SN - 1043-1802

VL - 35

SP - 1755

EP - 1761

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 11

ER -

A Diketopinic Reagent for the Reversible Bioconjugation to Arginine Residues on Native Antibodies

Abstract

Access to Document

Other files and links

Fingerprint

Cite this