Synthesis and activity of a folate peptide camptothecin prodrug

The synthesis and activity (IC 50 = 10 nM) of a folate peptide camptothecin prodrug with a disulfide carbonate releasable linker is reported. A folate receptor targeted camptothecin prodrug was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linke...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2006-10, Vol.16 (20), p.5350-5355
Hauptverfasser: Henne, Walter A., Doorneweerd, Derek D., Hilgenbrink, Andrew R., Kularatne, Sumith A., Low, Philip S.
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Sprache:eng
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Zusammenfassung:The synthesis and activity (IC 50 = 10 nM) of a folate peptide camptothecin prodrug with a disulfide carbonate releasable linker is reported. 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 IC 50 of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.07.076