Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases

Walter A. Henne, Sumith A. Kularatne, Wilfredo Ayala-López, Derek D. Doorneweerd, Torian W. Stinnette, Yingjuan Lu, Philip S. Low

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A folate receptor targeted didemnin B conjugate was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity and TNF-α inhibition in RAW264.7 macrophage-like cells exhibited IC 50s of 13 and 5 nM, respectively. Folate didemnin B was found to be ∼50-100 fold more potent than didemnin B itself. More importantly, activity of the prodrug was blocked by excess folic acid, demonstrating receptor-mediated cellular uptake of the conjugate.

Original languageEnglish (US)
Pages (from-to)709-712
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Folate
  • Folate didemnin B
  • Folate receptor
  • Inflammation
  • Macrophage

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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