Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesisTools Betts, Helen M., Sephton, Selena Milicevic, Tong, Carmen, Awais, Ramla, Hill, Philip J., Perkins, A.C. and Aigbirhio, Franklin I. (2016) Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis. Journal of Medicinal Chemistry, 59 (20). pp. 9422-9430. ISSN 1520-4804 Full text not available from this repository.
Official URL: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00968
AbstractThere is currently no ideal radiotracer for imaging protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18 labelled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabelled with the short half-life positron emitter carbon-11 which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis which identified fluoroethyl analogue (7b) as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in modest radiochemical yield 2±0.6% and excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.
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