Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis
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 prote...
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American Chemical Society
2016
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| Online Access: | https://eprints.nottingham.ac.uk/39443/ |
| _version_ | 1848795837399826432 |
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| author | Betts, Helen M. Sephton, Selena Milicevic Tong, Carmen Awais, Ramla Hill, Philip J. Perkins, A.C. Aigbirhio, Franklin I. |
| author_facet | Betts, Helen M. Sephton, Selena Milicevic Tong, Carmen Awais, Ramla Hill, Philip J. Perkins, A.C. Aigbirhio, Franklin I. |
| author_sort | Betts, Helen M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:38:26Z |
| format | Article |
| id | nottingham-39443 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T19:38:26Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-394432020-05-04T18:18:07Z https://eprints.nottingham.ac.uk/39443/ Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis Betts, Helen M. Sephton, Selena Milicevic Tong, Carmen Awais, Ramla Hill, Philip J. Perkins, A.C. Aigbirhio, Franklin I. 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. American Chemical Society 2016-10-03 Article PeerReviewed 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 Positron emission tomography; protein synthesis; puromycin; fluorine-18 http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00968 doi:10.1021/acs.jmedchem.6b00968 doi:10.1021/acs.jmedchem.6b00968 |
| spellingShingle | Positron emission tomography; protein synthesis; puromycin; fluorine-18 Betts, Helen M. Sephton, Selena Milicevic Tong, Carmen Awais, Ramla Hill, Philip J. Perkins, A.C. Aigbirhio, Franklin I. Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title | Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title_full | Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title_fullStr | Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title_full_unstemmed | Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title_short | Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis |
| title_sort | synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for pet imaging of protein synthesis |
| topic | Positron emission tomography; protein synthesis; puromycin; fluorine-18 |
| url | https://eprints.nottingham.ac.uk/39443/ https://eprints.nottingham.ac.uk/39443/ https://eprints.nottingham.ac.uk/39443/ |