一种新的al18f标记的nota修饰泛素29-41衍生物作为细菌感染PET显像剂

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2025-03-04 DOI:10.1016/j.ejmech.2025.117482

Yuhao Jiang , Qianna Wang , Junhong Feng , Guangxing Yin , Peiwen Han , Qing Ruan , Junbo Zhang

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引用次数: 0

摘要

抗菌肽泛素29-41 （TGRAKRRMQYNRR）是检测细菌感染的潜在靶点。合成了一种以赖氨酸氨基侧1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）修饰的新型UBI 29-41衍生物，并用Al18F进行放射性标记，命名为[18F]AlF-NOTA-UBI 29-41。新型PET示踪剂在室温生理盐水和37℃小鼠血清中均保持良好的体外稳定性。体外细菌结合实验表明，该示踪剂能特异性结合金黄色葡萄球菌。感染肌肉和发炎肌肉对[18F]AlF-NOTA-UBI 29-41的摄取在生物分布上有显著差异。细菌感染小鼠模型的PET成像研究显示，在感染部位可见积聚，表明该复合物是区分细菌感染和无菌炎症的潜在PET示踪剂。

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A novel Al18F-labelled NOTA-modified ubiquicidin 29-41 derivative as a bacterial infection PET imaging agent

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A novel Al18F-labelled NOTA-modified ubiquicidin 29-41 derivative as a bacterial infection PET imaging agent

The antimicrobial peptide ubiquicidin 29-41 (TGRAKRRMQYNRR) is a potential target for detecting bacterial infection. A novel UBI 29–41 derivative modified with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) on the amino side of lysine was synthesized and radiolabelled with Al¹⁸F, named [¹⁸F]AlF-NOTA-UBI 29–41. The novel PET tracer maintained good in vitro stability in saline at room temperature and mouse serum at 37 °C. In vitro bacterial binding experiments indicated that the tracer specifically bound to Staphylococcus aureus. A significant difference in the uptake of [¹⁸F]AlF-NOTA-UBI 29–41 between infected muscle and inflamed muscle was observed in biodistribution. A PET imaging study in mouse models with bacterial infection and sterile inflammation showed apparent accumulation at the infection site, suggesting that the complex is a potential PET tracer for distinguishing bacterial infection from sterile inflammation.

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.