| Autor: |
Holbrook RJ; Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States., Weinberg DJ, Peterson MD, Weiss EA, Meade TJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2015 Mar 11; Vol. 137 (9), pp. 3379-85. Date of Electronic Publication: 2015 Mar 02. |
| DOI: |
10.1021/jacs.5b00342 |
| Abstrakt: |
We describe a mechanism of light activation that initiates protein inhibitory action of a biologically inert Co(III) Schiff base (Co(III)-sb) complex. Photoinduced electron transfer (PET) occurs from a Ru(II) bipyridal complex to a covalently attached Co(III) complex and is gated by conformational changes that occur in tens of nanoseconds. Reduction of the Co(III)-sb by PET initiates displacement of the inert axial imidazole ligands, promoting coordination to active site histidines of α-thrombin. Upon exposure to 455 nm light, the rate of ligand exchange with 4-methylimidazole, a histidine mimic, increases by approximately 5-fold, as observed by NMR spectroscopy. Similarly, the rate of α-thrombin inhibition increases over 5-fold upon irradiation. These results convey a strategy for light activation of inorganic therapeutic agents through PET utilizing redox-active metal centers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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