Scientists modified chemical compounds to target mitochondria within cells, potentially increasing medication efficacy in drug development.
By Jaskiran Garcha
Scientists recently found a way to modify certain chemical compounds to target mitochondria within human body cells. This innovation of hydrophobic peptides brings with it the potential for developing more effective medications to treat multiple health diseases.
A collaborative effort
Breakthroughs do not happen independently, which was the case for the scientists who worked on a recent study from the Laboratory of Organic Chemistry at ETH Zürich, Switzerland.
Many years ago, scientists found that some chemicals can mix with water and others, like oil, do not. And some can do both. Specific chemical compounds with this ability that can also enter human body cells are known as cell-penetrating peptides (CPP). Scientists think these compounds can target the cell’s powerhouse. So, they found ways to modify the CPPs to help in drug development that only affects the mitochondria, also known as the powerhouse of the cell.
The long road
Specifically, in this new work, researchers found that modifying chemical compounds so that a large portion of them cannot dissolve in water, a property known as hydrophobicity, will help them selectively enter the mitochondria over other parts of the cells. This works because adding this region, along with other minor modifications, changes the structure of the chemical compound.
Before the chemical compounds target the mitochondria, they must enter the cell. Naturally, the cell regulates this process to ensure that unwanted and harmful materials do not enter it. So, in addition to exploring modifications that target the mitochondria, the researchers of this study also examined ways they can help these modified compounds enter the cell. They found that in addition to hydrophobic regions, the presence of specific positively charged chemical groups (i.e., guanidinium) improves the ability of CPP to enter the cell and reach the mitochondria.
Getting here was not easy, though. First, the researchers started with only a model CPP. They attached different chemical groups to increase its hydrophobicity. One of these groups, the one with the highest hydrophobicity, was considered the best at reaching the mitochondria. Then scientists added two of these chemical groups to the CPP, one on each end. This modification improved the ability of the CPP to enter the cells. Then they tested other chemical groups with similar properties to see if these were better at moving the CPP into the cell. One of these groups, similar to the first one but with additional cyclic chemical components attached to it, provided the best results. Many rounds of experiments finally led them to conclude that specifically modified CPPs can target the mitochondria, which could be invaluable for drug development.
RELATED: Scientists deliver precisely targeted medicine using ultrasound.
Why mitochondria?
Mitochondria are affected by many diseases, including diabetes and cancer. Alzheimer’s, the most common brain-related disease worldwide, is also related to disruptions in mitochondria. Therefore, mitochondria are a good choice for this study. If the new compounds are helpful, they might have a widespread positive influence on drug development.
RELATED: Alzheimer’s Disease, Medications, and You
Learn about related drug developments in Killing Cancer from the Inside.
Moving toward drug development
While performing many of the experiments mentioned above, the scientists determined that once the CPP enters the cell, it does not always remain in the same position. It changes its location over time. So, they decided to test this using two of the chemical groups not initially considered ideal because they did not reach the correct location inside the cell. These groups initially stayed at the edge of the cell upon entrance. Still, over time, they moved away and localized to the mitochondria. This information is significant because pharmaceutical companies may find it helpful during CPP-inspired drug development.
This study was published in the peer-reviewed journal ACS Chemical Biology.
References
Schmitt, A. M., & Wennemers, H. (2024). Amphipathic proline-rich cell penetrating peptides for mitochondria targeting. Proceedings of the 37th European Peptide Symposium, 1231. https://doi.org/10.17952/37eps.2024.p1231
Schmitt, A., & Wennemers, H. (2025). Amphipathic proline-rich cell penetrating peptides for mitochondria targeting. ACS Chemical Biology 20(9), 2298–2307. https://doi.org/10.1021/acschembio.5c00479
Featured image is Panorama view of golden mitochondria: “In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.” Credit: Torsten Wittmann, University of California, San Francisco; courtesy of NIH National Institute of General Medical Sciences.
About the Author
Jaskiran Garcha is a science communication enthusiast pursuing her graduate studies in Ontario, Canada. She enjoys research and wants to share it with everyone she can, often through articles like the one above. When not doing science, she likes to travel.
