Details

Autor(en) / Beteiligte

• Uno, Shinpei
• Harkiss, Alexander H.
• Chowdhury, Roy
• Caldwell, Stuart T.
• Prime, Tracy A.
• James, Andrew M.
• Gallagher, Brendan
• Prudent, Julien
• Hartley, Richard C.
• Murphy, Michael P.

Titel

Incorporating a Polyethyleneglycol Linker to Enhance the Hydrophilicity of Mitochondria‐Targeted Triphenylphosphonium Constructs

Ist Teil von

• Chembiochem : a European journal of chemical biology, 2023-06, Vol.24 (11), p.e202200774-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 (Δψm). 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. Triphenylphosphonium (TPP) cation is widely used for selective delivery of compounds into mitochondria. This study demonstrated that the replacement of an alkyl chain with polyethylene glycol (PEG) chain in TPP‐conjugated compounds can reduce the membrane adsorption of the compounds, leading to fine‐tuning of mitochondria targeting strategies.