title: Trivalent Gd-DOTA reagents for modification of proteins.
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.
authors.affiliation: 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.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Fisher
authors.affiliation: 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.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Williamson
authors.affiliation: 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.
authors.forename: George M
authors.initials: GM
authors.lastname: Burslem
authors.affiliation: 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.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Plante
authors.affiliation: Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
authors.forename: Iain W
authors.initials: IW
authors.lastname: Manfield
authors.affiliation: Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Tiede
authors.affiliation: Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Ault
authors.affiliation: Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stockley
authors.affiliation: Leeds Institute of Cardiovascular and Metabolic Medicine , University of Leeds , UK ; Multidisciplinary Cardiovascular Research Centre , University of Leeds , UK.
authors.forename: Sven
authors.initials: S
authors.lastname: Plein
authors.affiliation: Leeds Institute of Cardiovascular and Metabolic Medicine , University of Leeds , UK ; Multidisciplinary Cardiovascular Research Centre , University of Leeds , UK.
authors.forename: Azhar
authors.initials: A
authors.lastname: Maqbool
authors.affiliation: Astbury Centre for Structural Molecular Biology , University of Leeds , UK ; School of Molecular and Cellular Biology , University of Leeds , UK.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Tomlinson
authors.affiliation: 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.
authors.forename: Richard
authors.initials: R
authors.lastname: Foster
authors.affiliation: 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.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Warriner
authors.affiliation: 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.
authors.forename: Robin S
authors.initials: RS
authors.lastname: Bon