Journal
PEPTIDE SCIENCE
Volume 114, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/pep2.24239
Keywords
amphipathic peptoid; cell-penetrating peptoid; mitochondria; mitochondrial delivery
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Funding
- Gwangju Institute of Science and Technology: GIST Research Institute GIST-CNUH Research Collaboration grant 2021
- National Research Foundation of Korea [NRF-2018R1D1A1B07042846, NRF-2021R1A2C2014421]
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Two types of mitochondria-targeted delivery methods are discussed in the text. Peptoids, biocompatible peptidomimetics, may have potential applications in various fields such as anti-cancer or antibacterial activity. Increasing hydrophobicity did not enhance mitochondrial localization, while a positive net charge was crucial for the process.
Mitochondria-targeted delivery methods offer a straightforward approach for studying mitochondria-related diseases and potentially streamlining therapeutic development. Peptoids (oligo-N-substituted glycines) are biocompatible peptidomimetics that display similar physicochemical properties as peptides with the added advantage of enhanced resistance to proteolytic cleavage. In particular, amphipathic peptoids are membrane-permeable and their cationic charges and hydrophobicity can be readily modified for specific purposes, such as cell penetration, anti-cancer or antibacterial activity. Previously, we identified a series of amphipathic peptoids that showed efficient cell penetration and mitochondrial localization. As a continued effort to identify selective mitochondrial transporters, we designed new analogs with varying hydrophobicity and net charges. We observed that overall increase in hydrophobicity did not result in enhanced mitochondrial localization while maintaining high cell permeability. Moreover, a certain degree of a positive net charge was critical for mitochondrial localization. In conclusion, our mitochondria-targeting peptoids provide a highly selective and robust delivery system for bioactive molecules.
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