生物素介导的药物递送:生物素转运体是否介导生物素偶联物的摄取?

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ravi Tripathi, Xiaoxiao Yang, Dongning Liu, Wen Lu, Binghe Wang
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引用次数: 0

摘要

钠依赖性多重维生素转运体(SMVT)是一种在多种类型癌细胞中过度表达的生物素转运体,通常被研究用于使用生物素偶联物靶向药物递送。然而,这种缀合物缺乏被SMVT识别所需的羧基。以前,我们提出SMVT不太可能是生物素缀合物的转运体。为了通过实验评估这一假设,我们在细胞培养中检测了生物素偶联的CO前药对在细胞内的富集和激活。虽然观察到SMVT过表达细胞的前药富集,但这种富集不受过量生物素的影响,表明SMVT缺乏竞争。此外,两种缺乏羧基的生物素类似物表现出增强或抑制作用,这取决于特定的结构特征。这些发现支持了SMVT不是生物素偶联物转运体的观点,并强调了对生物素偶联物转运机制的进一步机制研究的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biotin-mediated drug delivery: does the biotin transporter mediate uptake of biotin conjugates?

Biotin-mediated drug delivery: does the biotin transporter mediate uptake of biotin conjugates?

Biotin-mediated drug delivery: does the biotin transporter mediate uptake of biotin conjugates?

Biotin-mediated drug delivery: does the biotin transporter mediate uptake of biotin conjugates?

Sodium-dependent multivitamin transporter (SMVT) is a biotin transporter over-expressed in various types of cancer cells and is commonly studied for targeted drug delivery using biotin conjugates. However, such conjugates lack the carboxyl group needed for recognition by SMVT. Previously, we proposed that SMVT is unlikely the transporter of biotin conjugates. To experimentally assess this hypothesis, we examined intracellular enrichment and activation of the biotin-conjugated version of a well-established CO prodrug pair in cell culture. Although prodrug enrichment in SMVT-over-expressing cells was observed, this enrichment was not affected by excess biotin, indicating the lack of competition for SMVT. Additionally, two biotin analogs lacking the carboxyl group exhibited either augmentative or inhibitory effects depending on specific structural features. These findings support the notion that SMVT is not the transporter of biotin conjugates and underscore the need for further mechanistic studies of the transport mechanism(s) of biotin conjugates.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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