Chemoselective ¹⁸F-incorporation into pyridyl acyltrifluoroborates for rapid radiolabelling of peptides and proteins at room temperature

Abstract

A new prosthetic group is reported for quantitative 18F-labelling of peptides and proteins based on the chemoselective ligation of potassium acyltrifluoroborates (KATs) and hydroxylamines without any detectable 18F/19F isotope exchange at the KAT moiety.

Recent Advances in the Synthesis of Acylboranes and Their Widening Applicability

“…This was achieved by Bode, Ametamey, and co-workers, who introduced an 18 F-atom to the 6-position of 6-bromo-3-pyridyl KAT by nucleophilic substitution. 22 The reaction proceeded without competitive substitution of fluorine atoms in the trifluoroborate moiety. This compound served as a prosthetic group for radiolabeling of peptides and proteins.…”

Synthesis of Acylboron Compounds

“…[19] Ametamey,B ode and co-workers recently reported the 18 Fi ncorporation onto bromo-pyridyl KATderivatives in decent yields.Interestingly, no fluoride exchange took place on the acyltrifluoroborate groups.K AT 5 was then used for the 18 Fisotope labelling of protein and peptides for in vivo PET/CT imaging (Scheme 3). [20] Theamide-forming ligation of acylboronates and hydroxylamines is ar are reaction in which bond cleavage occurs at both reactants in the absence of ac atalyst. By attaching desthiobiotin to both hydroxylamine 6 and monofluoro acylboronates 7 and using streptavidin as atemplate,ligation at submicromolar concentrations occurs efficiently (Scheme 4a).…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January–June 2020)

“…To overcome this, Chiotellis and colleagues report chemoselective 18 F-incorporation into pyridyl acyltrifluoroborates, and demonstrate rapid (15 min) and quantitative radiolabeling of peptides and proteins through an amide bond (via hydroxylamine precursors) at room temperature under mild aqueous conditions as shown in Fig. 8 (Chiotellis et al 2020 ). Common protein and peptide functionality is tolerated without need for protecting groups, suggesting the orthogonal radiolabeling strategy could become a method of choice for radiofluorinating peptides and proteins in the future.…”

“…8 Radiolabeling of peptides and proteins using 6-[ 18 F]fluoropyridyl acyltrifluoroborate ([ 18 F]FPAT). This figure was originally published by Chiotellis et al ( 2020 ) this article was licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License and published by The Royal Society of Chemistry …”