Synthesis and activity of a folate peptide camptothecin prodrug

被引：136

作者：

Henne, Walter A.

Doorneweerd, Derek D.

Hilgenbrink, Andrew R.

Kularatne, Sumith A.

Low, Philip S. ^{[1
]}

机构：

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

[2] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 20期

关键词：

folate; folic acid; camptothecin; targeted drug delivery; endocytosis; releasable linker; peptide; prodrug; carbonate; disulfide;

D O I：

10.1016/j.bmcl.2006.07.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A folate receptor targeted camptothecin prodrug was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. The conjugate was found to possess high affinity for folate receptor-expressing cells and inhibited cell proliferation in human KB cells with an IC50 of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake. (c) 2006 Elsevier Ltd. All rights reserved.

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页码：5350 / 5355

页数：6

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