2. Academic Validation
  3. Trivalent Gd-DOTA reagents for modification of proteins

Trivalent Gd-DOTA reagents for modification of proteins

  • RSC Adv. 2015 Dec 9;5(116):96194-96200. doi: 10.1039/c5ra20359g.
Martin J Fisher 1,  Daniel J Williamson 1,  George M Burslem 1,  Jeffrey P Plante 1,  Iain W Manfield 2,  Christian Tiede 2,  James R Ault 2,  Peter G Stockley 2,  Sven Plein 3,  Azhar Maqbool 3,  Darren C Tomlinson 2,  Richard Foster 4,  Stuart L Warriner 1,  Robin S Bon 5
Affiliations

Affiliations

  • 1 School of Chemistry , University of Leeds , LS2 9JT , UK . Email: r.bon@leeds.ac.uk; Astbury Centre for Structural Molecular Biology , University of Leeds , UK.
  • 2 Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
  • 3 Leeds Institute of Cardiovascular and Metabolic Medicine , University of Leeds , UK ; Multidisciplinary Cardiovascular Research Centre , University of Leeds , UK.
  • 4 School of Chemistry , University of Leeds , LS2 9JT , UK . Email: r.bon@leeds.ac.uk; Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; Multidisciplinary Cardiovascular Research Centre , University of Leeds , UK.
  • 5 School of Chemistry , University of Leeds , LS2 9JT , UK . Email: r.bon@leeds.ac.uk; Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; Leeds Institute of Cardiovascular and Metabolic Medicine , University of Leeds , UK ; Multidisciplinary Cardiovascular Research Centre , University of Leeds , UK.
PMID: 27019702 DOI: 10.1039/c5ra20359g
Abstract

The development of novel protein-targeted MRI contrast agents crucially depends on the ability to derivatise suitable targeting moieties with a high payload of relaxation enhancer (e.g., gadolinium(iii) complexes such as Gd-DOTA), without losing affinity for the target proteins. Here, we report robust synthetic procedures for the preparation of trivalent Gd-DOTA reagents with various chemical handles for site-specific modification of biomolecules. The reagents were shown to successfully label proteins through isothiocyanate ligation or through site-specific thiol-maleimide ligation and strain-promoted azide-alkyne cycloaddition.

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