Uno, S., Harkiss, A. H., Chowdhury, R., Caldwell, S. T. , Prime, T. A., James, A. M., Gallagher, B., Prudent, J., Hartley, R. C. and Murphy, M. P. (2023) Incorporating a polyethyleneglycol linker to enhance the hydrophilicity of mitochondria‐targeted triphenylphosphonium constructs. ChemBioChem, 24(11), e202200774. (doi: 10.1002/cbic.202200774) (PMID:36917207)
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Abstract
The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Dym). Typically, a simple alkane links the TPP to its “cargo”, increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Medical Research Council UK (MC_UU_00028/4) and by Wellcome Trust Investigator awards to MPM (220257/Z/20/Z) and RCH (220257/B/20/Z). JP was supported by the Medical Research Council UK (MC_UU_00028/5). BG's PhD studentship was supported by the Engineering and Physical Sciences Research Council (EP/R513222/1). SU was supported by an Overseas fellowship from Japan Society for the Promotion of Science (202260220). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Caldwell, Dr Stuart and Hartley, Professor Richard and Harkiss, Dr Alexander |
| Authors: | Uno, S., Harkiss, A. H., Chowdhury, R., Caldwell, S. T., Prime, T. A., James, A. M., Gallagher, B., Prudent, J., Hartley, R. C., and Murphy, M. P. |
| College/School: | College of Science and Engineering > School of Chemistry |
| Journal Name: | ChemBioChem |
| Publisher: | Wiley |
| ISSN: | 1439-4227 |
| ISSN (Online): | 1439-7633 |
| Published Online: | 14 March 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in ChemBioChem 24(11): e202200774 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Data DOI: | 10.5525/gla.researchdata.1385 |
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