Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry.
Chembiochem
; 17(14): 1312-6, 2016 07 15.
Article
in En
| MEDLINE
| ID: mdl-27124570
ABSTRACT
Mitochondria are central to health and disease, hence there is considerable interest in developing mitochondria-targeted therapies that require the delivery of peptides or nucleic acid oligomers. However, progress has been impeded by the lack of a measure of mitochondrial import of these molecules. Here, we address this need by quantitatively detecting molecules within the mitochondrial matrix. We used a mitochondria- targeted cyclooctyne (MitoOct) that accumulates several- hundredfold in the matrix, driven by the membrane potential. There, MitoOct reacts through click chemistry with an azide on the target molecule to form a diagnostic product that can be quantified by mass spectrometry. Because the membrane potential-dependent MitoOct concentration in the matrix is essential for conjugation, we can now determine definitively whether a putative mitochondrion-targeted molecule reaches the matrix. This "ClickIn" approach will facilitate development of mitochondria-targeted therapies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Delivery Systems
/
Click Chemistry
/
Mitochondria
Limits:
Humans
Language:
En
Journal:
Chembiochem
Journal subject:
BIOQUIMICA
Year:
2016
Document type:
Article
Affiliation country:
United kingdom