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Typically, a simple alkane links the TPP to its \u201ccargo\u201d, increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria\u2010targeted 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\u2010facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria\u2010targeted TPP compounds within mitochondria to be fine\u2010tuned.<\/jats:p>","DOI":"10.1002\/cbic.202200774","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T11:59:58Z","timestamp":1678795198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Incorporating a Polyethyleneglycol Linker to Enhance the Hydrophilicity of Mitochondria\u2010Targeted Triphenylphosphonium Constructs"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1200-2918","authenticated-orcid":false,"given":"Shinpei","family":"Uno","sequence":"first","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H.","family":"Harkiss","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart T.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Prime","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"James","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Gallagher","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Prudent","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Hartley","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-9618","authenticated-orcid":false,"given":"Michael P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge CB2 0XY UK"},{"name":"Department of Medicine University of Cambridge  Cambridge CB2 0QQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.174"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3969"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201915826"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201915826"},{"key":"e_1_2_8_4_1","first-page":"222","volume":"70","author":"Ross M. 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