Synthesis and activity of a folate peptide camptothecin prodrug

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

    Research output: Contribution to journalArticlepeer-review

    143 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 languageEnglish (US)
    Pages (from-to)5350-5355
    Number of pages6
    JournalBioorganic and Medicinal Chemistry Letters
    Volume16
    Issue number20
    DOIs
    StatePublished - 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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