Nanoreporter of an Enzymatic Suicide Inactivation Pathway.
Nano Lett
; 20(11): 7819-7827, 2020 11 11.
Article
in En
| MEDLINE
| ID: mdl-33119310
ABSTRACT
Enzymatic suicide inactivation, a route of permanent enzyme inhibition, is the mechanism of action for a wide array of pharmaceuticals. Here, we developed the first nanosensor that selectively reports the suicide inactivation pathway of an enzyme. The sensor is based on modulation of the near-infrared fluorescence of an enzyme-bound carbon nanotube. The nanosensor responded selectively to substrate-mediated suicide inactivation of the tyrosinase enzyme via bathochromic shifting of the nanotube emission wavelength. Mechanistic investigations revealed that singlet oxygen generated by the suicide inactivation pathway induced the response. We used the nanosensor to quantify the degree of enzymatic inactivation by measuring response rates to small molecule tyrosinase modulators. This work resulted in a new capability of interrogating a specific route of enzymatic death. Potential applications include drug screening and hit-validation for compounds that elicit or inhibit enzymatic inactivation and single-molecule measurements to assess population heterogeneity in enzyme activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monophenol Monooxygenase
/
Nanotubes, Carbon
Limits:
Humans
Language:
En
Journal:
Nano Lett
Year:
2020
Type:
Article
Affiliation country:
United States