[18F]-5-Fluoro-5-deoxyribose, an efficient peptide bioconjugation ligand for positron emission tomography (PET) imaging

Abstract

[(18)F]-5-Fluoro-5-deoxyribose ([(18)F]-FDR) conjugates much more rapidly than [(18)F]-FDG under mild reaction conditions to peptides and offers new prospects for mild and rapid bioconjugation for fluorine-18 labelling in PET imaging.

Oxime formation for fluorine-18 labeling of peptides and proteins for positron emission tomography (PET) imaging: A review

“…As an extension of the previous work, 5-[ 18 F]fluoro-5-deoxyribose ([ 18 F]FDR) has been used as an efficient prosthetic group for peptide conjugation [59]. As an example, [ 18 F]FDR was conjugated with the aminooxy-functionalized hexapeptide agonist (compound 23) of the human protease activated receptor 2 (PAR-2) in sodium acetate buffer (pH 4.6), with 95% conversion at room temperature in 10 min (Scheme 12).…”

Sweetening Pharmaceutical Radiochemistry by18F-Fluoroglycosylation: A Short Review

“…In the endeavor to improve the oxime conjugation step, 5-[ 18 F]fluoro-5-deoxyribose ([ 18 F]FDR) has been considered as an alternative prosthetic group (Scheme 4) [36, 37, 55, 56]. The idea is that, in comparison to [ 18 F]FDG, the 5-membered ring sugar [ 18 F]FDR with the fluorine at C-5 instead of C-6 favors the ring opening of the sugar to the aldehydic form and therefore promotes the oxime ligation with aminooxy-functionalized peptides even under mild reaction conditions, such as ambient temperature and less acidic pH of 4.6.…”

“…After HPLC isolation, which turned out to be essential for separation of free ribose from the 18 F-labeled product, the resulting methyl 2,3- O -isopropylidene-5-deoxy-5-[ 18 F]fluororibofuranoside ( 37 , Scheme 4) is hydrolyzed with aqueous HCl and purified by solid phase extraction. The average RCY for [ 18 F]FDR is about 35% and the radiosynthesis takes 85 min [37, 55]. This ribose-free sugar was used for the conjugation of the two aminooxy-functionalized RGD peptides c(RGDfK) and c(RGDfC) [36], which were conjugated at room temperature in sodium acetate buffer at pH 4.6.…”

Development of Halogenase Enzymes for Use in Synthesis

“…370,374 101 is of particular interest because of the potential to exploit this primed substrate in bio-conjugation due to its propensity for ring-opening. 375,376 Bio-conjugation has also been achieved by using nucleotide mimics containing chemical handles for conjugation onto a peptide target. 377,378 It was noted by crystallography that H2 of the adenine ring of SAM was positioned towards the surface of the enzyme, suggesting that analogues with substitution here may be accepted by the fluorinase.…”