Engineered apoptosis-inducing peptides with enhanced mitochondrial localization and potency

Kristin L. Horton, Shana O. Kelley

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Apoptosis-inducing peptides that trigger mitochondrial disruption are a popular tool in pharmaceutical and anticancer research. While useful, their potencies are low, which impedes further development of drugs based on these sequences. Here, we describe an effort to engineer the intracellular localization and activity of a peptide with known anticancer activity, D-(KLAKLAK)2, to improve potency by increasing the specificity of the peptide for mitochondria and enhancing disruption of this organelle. The engineered peptides are significantly more toxic to a wide variety of cancer cell lines, with the best analogue exhibiting a LC50 value 100-fold lower than the parent compound. Importantly, the peptides maintain their potency when made cell-type specific.

Original languageEnglish (US)
Pages (from-to)3293-3299
Number of pages7
JournalJournal of Medicinal Chemistry
Issue number10
StatePublished - May 28 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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