Multiple triphenylphosphonium cations shuttle a hydrophilic peptide into mitochondria

Shareefa E. Abu-Gosh, Netanel Kolvazon, Boaz Tirosh, Israel Ringel, Eylon Yavin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


A variety of diseases are related to mitochondrial dysfunction. Hence, the ability to transport drugs to mitochondria that are otherwise cell impermeable would be of great therapeutic potential. Triphenylphosphonium (TPP) cations have been shown to accumulate in mitochondria when attached to small molecules. Here we report on the consequence of increasing the number of TPP moieties that are covalently linked to a model hydrophilic peptide Hemagglutinin A (HA). By extending the HA peptide with L-lysine amino acids to which the TPP's are covalently linked through the ε-amine, we have systematically synthesized the HA peptide with 0-3 TPP's. All peptides were subsequently labeled with FITC at the N-terminus. Cellular uptake and mitochondrial localization of the HA-TPP conjugates in HeLa cells were profoundly augmented with increasing number of TPPs, suggesting that this approach is applicable for the delivery of peptides. Furthermore, confocal microscopy demonstrated that the peptides localize to mitochondria. Importantly, all peptide conjugates did not show apparent toxicity at concentrations that are several orders of magnitude higher than those used for HA peptide delivery.

Original languageAmerican English
Pages (from-to)1138-1144
Number of pages7
JournalMolecular Pharmaceutics
Issue number4
StatePublished - 3 Aug 2009


  • Delivery
  • Lipophilic peptide
  • Mitochondria
  • Triphenylphosphonium (TPP) cations


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