Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis

Betts, Helen M. and Sephton, Selena Milicevic and Tong, Carmen and Awais, Ramla and Hill, Philip J. and 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

[img] PDF - Repository staff only until 3 October 2017. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1MB)

Abstract

There 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.

Item Type: Article
Additional Information: This is the author's version of a submitted work that was subsequently accepted for publication in the Journal of Medicinal Chemistry, c2016 American Chemical Society under the title Synthesis, in Vitro Evaluation, and Radiolabeling of Fluorinated Puromycin Analogues: Potential Candidates for PET Imaging of Protein Synthesis. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00968
Keywords: Positron emission tomography; protein synthesis; puromycin; fluorine-18
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1021/acs.jmedchem.6b00968
Depositing User: Eprints, Support
Date Deposited: 19 Dec 2016 14:34
Last Modified: 13 Jul 2017 07:30
URI: http://eprints.nottingham.ac.uk/id/eprint/39443

Actions (Archive Staff Only)

Edit View Edit View