A small-molecule pretargeting approach for PSMA-targeted conjugates

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-28 DOI:10.1016/j.bmcl.2025.130213

Nooshin Mesbahi, Hosog Yoon, Melody D. Fulton, Clifford E. Berkman

引用次数: 0

Abstract

We developed pretargeting approach for the targeted delivery of molecular payloads to prostate cancer cells expressing the hallmark enzyme-biomarker, prostate-specific membrane antigen (PSMA). We employed a phosphoramidate-based PSMA ligand (CTT1298) with a click-ready DBCO group for strain-promoted azide-alkyne cycloaddition (SPAAC) and used 6-FAM-Azide as a model payload. PSMA+ cells were treated with a fluorescent PSMA-targeted probe (FAM-C6–1298), confirming delivery and accumulation. Further, live-cell experiments with DBCO-C6–1298 and 5-FAM-azide demonstrated selective pretargeted delivery. These results validate the feasibility of this pretargeting strategy in PSMA+ cells, suggesting its potential for preclinical applications with therapeutic and diagnostic payloads, enhancing the specificity and safety of prostate cancer treatments.

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psma靶向偶联物的小分子预靶向方法。

我们开发了一种预先靶向的方法，将分子有效载荷靶向递送到表达标志性酶生物标志物前列腺特异性膜抗原（PSMA）的前列腺癌细胞。我们采用磷酸基PSMA配体（CTT1298）和可点击DBCO基团用于菌株促进叠氮化物-炔环加成（SPAAC），并以6- fam -叠氮化物作为模型有效载荷。PSMA+细胞用荧光PSMA靶向探针（FAM-C6-1298）处理，确认传递和积累。此外，DBCO-C6-1298和5- fam -叠氮化物的活细胞实验证明了选择性预靶向递送。这些结果验证了这种预靶向策略在PSMA+细胞中的可行性，表明其在治疗和诊断有效载荷方面的临床前应用潜力，增强了前列腺癌治疗的特异性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.