Synthesis, in Vitro Evaluation, and Radiolabeling of Fluorinated Puromycin Analogues: Potential Candidates for PET Imaging of Protein Synthesis.
J Med Chem
; 59(20): 9422-9430, 2016 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-27690460
ABSTRACT
There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled 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 radiolabeled 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 the fluoroethyl analogue 7b as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in a modest radiochemical yield of 2 ± 0.6% with excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Biossíntese de Proteínas
/
Puromicina
/
Tomografia por Emissão de Pósitrons
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article