Synthesis and activity of a folate peptide camptothecin prodrug

Walter A. Henne; Derek D. Doorneweerd; Andrew R. Hilgenbrink; Sumith A. Kularatne; Philip Low

doi:10.1016/j.bmcl.2006.07.076

Synthesis and activity of a folate peptide camptothecin prodrug

Walter A. Henne, Derek D. Doorneweerd, Andrew R. Hilgenbrink, Sumith A. Kularatne, Philip Low

Research output: Contribution to journal › Article

119 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	5350-5355
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2006.07.076
State	Published - Oct 15 2006

Keywords

Camptothecin
Carbonate
Disulfide
Endocytosis
Folate
Folic acid
Peptide
Prodrug
Releasable linker
Targeted drug delivery

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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abstract = "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.",

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AU - Doorneweerd, Derek D.

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AU - Kularatne, Sumith A.

AU - Low, Philip

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KW - Releasable linker

KW - Targeted drug delivery

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