Development of Novel Peptides for Mitochondrial Drug Delivery: Amino Acids Featuring Delocalized Lipophilic Cations
- Shana O. KelleyAffiliated withDepartment of Biochemistry, Faculty of Medicine, University of TorontoDepartment of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy, University of Toronto Email author
- , Kelly M. StewartAffiliated withDepartment of Biochemistry, Faculty of Medicine, University of Toronto
- , Rida MourtadaAffiliated withDepartment of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy, University of Toronto
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To create a new class of mitochondria-penetrating peptides (MPPs) that would facilitate drug delivery into the organelle through the inclusion of delocalized lipophilic cations (DLCs) in the peptide sequence.
We synthesized two novel amino acids featuring DLCs and incorporated them into peptides. Systematic studies were conducted to compare peptides containing these residues to those with natural cationic amino acids. Diastereomers were compared to determine the most advantageous arrangement for these peptides. Peptide lipophilicity, cellular uptake and mitochondrial specificity were compared for a variety of peptides.
Synthetic DLC residues were found to increase mitochondrial localization of MPPs due to higher overall hydrophobicity. MPP stereochemistry was important for cellular uptake rather than subcellular localization. This study reaffirmed the importance of uniform overall charge distribution for mitochondrial specificity.
DLCs can be incorporated into synthetic peptides and facilitate mitochondrial drug delivery. Lipophilicity and charge distribution must be carefully balanced to ensure localization within mitochondria.
KEY WORDScell-penetrating peptides drug delivery mitochondria mitochondria-penetrating peptides
- Development of Novel Peptides for Mitochondrial Drug Delivery: Amino Acids Featuring Delocalized Lipophilic Cations
- Online Date
- August 2011
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- cell-penetrating peptides
- drug delivery
- mitochondria-penetrating peptides
- Industry Sectors
- Author Affiliations
- 1. Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, M5S 3M2, Canada
- 2. Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S 3M2, Canada