Optimization of a Stable Linker Involved DEVD Peptide-Doxorubicin Conjugate That Is Activated upon Radiation-Induced Caspase-3-Mediated Apoptosis

Seung Woo Chung, Beom Suk Lee, Jeong Uk Choi, Seong Who Kim, In-San Kim, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

13 Citations (Scopus)


The current study demonstrates the process of selecting an optimal structure for a caspase-3-cleavable doxorubicin prodrug that could be synthesized by simple chemistry in high yields. The prodrug was intended to activate in the presence of caspase-3, whose expression can be exogenously regulated by inducing apoptosis with radiation therapy at a specific site of interest. For this purpose, doxorubicin was conjugated with a DEVD peptide via a heterobifunctional linker. Since the active form of the prodrug comprises the linker besides doxorubicin, we tested several different linkers and selected EMCS based on the examination of its in vitro biological activities. Consequently, DEVD-cysteamide-EMCS-doxorubicin was synthesized as the final compound. According to the various in vitro and in vivo studies, the synthesized prodrug was highly selective for tumors when coupled with radiation therapy, with the added benefit of ease of production. (Figure Presented).

Original languageEnglish
Pages (from-to)6435-6447
Number of pages13
JournalJournal of Medicinal Chemistry
Issue number16
Publication statusPublished - 2015 Aug 27
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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