Site‐specific addition of an ¹⁸F‐N‐methylaminooxy‐containing prosthetic group to a vinylsulfone modified peptide

Abstract

Numerous strategies employing prosthetic groups for the radiosynthesis of 18 F-fluorinated peptides for positron emission tomography have been investigated in recent years. We have previously reported a novel [18 F]prosthetic group bearing the N-methylaminooxy functionality capable of reacting in a site-selective manner with peptides functionalized with Michaelacceptors. In a further extension of this methodology we demonstrate that18 F]4, reacts chemoselectively with a vinylsulfone functionalized peptide. The conjugation yields were studied with respect to reaction time, level of radioactivity, peptide concentration and purity of the [18 F]prosthetic group used in the conjugation reaction. Incubation at 701C gave conjugation yields of around 80% with high radiochemical purity after 70 min at pH 5 in acetate buffer.

Emerging Role of ImmunoPET in Receptor Targeted Cancer Therapy

“…Widely available PET tracer 2-deoxy-2-[ 18 F]fluoro-D-glucopyranose (FDG) was also conjugated to aminooxy modified peptides [32]. To overcome the high reactivity of aminooxy group peptides modified with various electrophiles such as maleimide and vinylsulfone were conjugated with 18 F-fluorinated prosthetic group bearing N-methylaminooxy moiety [33,34]. Another class of fully orthogonal methods utilizes copper-I catalyzed 1,3-dipolar cycloaddition (CuAAC) to couple alkyne or azide decorated peptides with 18 F-fluorinated azides or alkynes [35,36].…”

New F-18 Prosthetic Group via Oxime Coupling

“…The incorporation of these groups onto a target molecule can be achieved by methods that include the formation of an acyl (7–12), sulfide (13–16), alkyl (17–20), hydrozone (21) or oxime (9, 22–31) bond formation, or with the use of photochemistry (32) and click chemistry (33–36). Most of these prosthetic ligands are not ideal for routine applications because they require time consuming and labor intense procedures with tedious purification processes.…”

“…R f = 0.28 (8.5:1.5:0.1 dichloromethane/methanol/ammonium hydroxide). 1 Dicarbamate (20). Amine 17 (37 mg, 0.06 mmol) dissolved in 2 mL of anhydrous N,N-dimethyl formamide was added to succinimide 18 (24 mg, 0.08 mmol) in a flame-dried 10 mL round-bottom flask.…”

“…N,N-Diethyl iso-propyl amine (0.22 mL, 163 mg, 1.26 mmol) was then added to the reaction mixture and allowed to stir at room temperature. After 1 h, the reaction was concentrated (23 mbar at 60 °C, to facilitate the removal of N,Ndimethyl formamide) and purified by flash chromatography (2À4% methanol/dichloromethane) to provide 29 mg (60%) of dicarbamate (20), a clear, gummy compound. R f = 0.31 (5% methanol/dichloromethane).…”

“…Several prosthetic ligands have been used with compounds that otherwise could not be labeled via a direct fluoride-18 nucleophilic substitution. The incorporation of these groups onto a target molecule can be achieved by methods that include the formation of an acyl, − sulfide, − alkyl, − hydrozone, or oxime ,− bond formation, or with the use of photochemistry and click chemistry. − Most of these prosthetic ligands are not ideal for routine applications because they require time-consuming and labor-intensive procedures with tedious purification processes. In general, prosthetic ligands may also be restricted to the type of substrate used when coupled with the target ligand due to interfering nucleophilic groups.…”