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Light-activated protein-conjugation and 89Zr-radiolabelling with water-soluble desferrioxamine derivatives

Guillou, Amaury; Earley, Daniel; Holland, Jason Philip (2020). Light-activated protein-conjugation and 89Zr-radiolabelling with water-soluble desferrioxamine derivatives. Chemistry - A European Journal, 26(32):7185-7189.

Abstract

Protein‐conjugates are vital tools in biomedical research, drug discovery and imaging science. For example, functionalised monoclonal antibodies (mAbs) coupled to the desferrioxamine B (DFO) chelate and radiolabelled with 89Zr are used as radiopharmaceuticals for diagnostic positron emission tomography (PET). In this context, protein functionalisation requires the formation of a covalent bond which must be achieved without compromising the biological properties of the mAb. Photochemistry offers new synthetic routes toward protein‐conjugates like 89Zr‐mAbs but to harness the potential of light‐induced conjugation reactions new photoactivatable reagents are required. Here, we introduce two photoactivatable DFO‐derivatives functionalised with an aryl azide (ArN3) for use in light‐activated conjugation and radiosynthesis of 89Zr‐mAbs. Incorporation of a tris‐polyethylene glycol (PEG)3 linker between DFO and the ArN3 group furnished water‐soluble chelates that were used in the one‐pot, photoradiosynthesis of different 89Zr‐radiolabelled protein‐conjugates with radiochemical yields up to 72.9±1.9%. Notably, the DFO‐PEG3 chelates can be readily synthesised in accordance with Good Laboratory Practice (GLP), which will facilitate clinical trials with photoradiolabelled 89Zr‐mAbs.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > Organic Chemistry
Uncontrolled Keywords:General Chemistry
Language:English
Date:5 June 2020
Deposited On:17 Apr 2020 09:41
Last Modified:23 Oct 2024 01:38
Publisher:Wiley-VCH Verlag
ISSN:0947-6539
OA Status:Green
Publisher DOI:https://doi.org/10.1002/chem.202001755
Project Information:
  • Funder: SNSF
  • Grant ID: PP00P2_163683
  • Project Title: Advanced radiochemical methods for multi-modal imaging with nanomedicines
  • Funder: SNSF
  • Grant ID: PP00P2_190093
  • Project Title:
  • Funder: Krebsliga
  • Grant ID: KLS-4257-08-2017
  • Project Title:
  • Funder: H2020
  • Grant ID: 676904
  • Project Title: Developing multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
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