Journal article
Stability of Phenyl-Modified Triphenylphosphonium Conjugates and Interactions with DTPA
ACS omega, Vol.7(51), pp.48332-48339
12/27/2022
DOI: 10.1021/acsomega.2c06525
PMCID: PMC9798776
PMID: 36591157
Appears in UI Libraries Support Open Access
Abstract
Triphenylphosphonium (TPP+) conjugates are effective in targeting drugs and probes to the mitochondria due to their lipophilic character that allows them to readily cross membranes and their large cationic radius that enables mitochondrial uptake because of the mitochondria’s negative membrane potential. TPP+ conjugates, while effectively sequestered by the mitochondria, are also known to uncouple oxidative phosphorylation (OXPHOS) and depolarize the mitochondrial membrane. xTPP+ conjugates with para-substitutions of functional groups on the phenyl rings of the TPP+ moiety display different levels of dose-mediated cytotoxicity due to differing potencies of uncoupling. xTPP+ conjugates having a para CF3 group substituted on the phenyl rings have been shown to afford significantly reduced uncoupling potency. In the present study, the analysis of a CF3-TPP+ conjugate with a decyl linker for stability revealed instability specific to the presence of DMSO in aqueous alkaline buffer. It is also demonstrated that the metal chelator, DTPA, forms a noncovalent protective complex with TPP+ moieties and prevents degradation of the CF3-TPP+ conjugate in aqueous DMSO. The stability of different xTPP+ conjugates and their interactions with DTPA are reported.
Details
- Title: Subtitle
- Stability of Phenyl-Modified Triphenylphosphonium Conjugates and Interactions with DTPA
- Creators
- Hannah K. Gruenwald - University of IowaRobert J. Kerns - University of Iowa
- Resource Type
- Journal article
- Publication Details
- ACS omega, Vol.7(51), pp.48332-48339
- DOI
- 10.1021/acsomega.2c06525
- PMID
- 36591157
- PMCID
- PMC9798776
- NLM abbreviation
- ACS Omega
- ISSN
- 2470-1343
- eISSN
- 2470-1343
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: T32 GM008365; DOI: 10.13039/100012675, name: University of Iowa Center for Biocatalysis and Bioprocessing
- Language
- English
- Date published
- 12/27/2022
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984361601902771
Metrics
16 Record Views