Nanoreporter of an enzymatic suicide inactivation pathway Research Letter


Authors: Yaari, Z.; Cheung, J. M.; Baker, H. A.; Frederiksen, R. S.; Jena, P. V.; Horoszko, C. P.; Jiao, F.; Scheuring, S.; Luo, M.; Heller, D. A.
Title: Nanoreporter of an enzymatic suicide inactivation pathway
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.
Keywords: drug screening; enzymology; drug development; reactive oxygen species; high throughput assay
Journal Title: Nano Letters
Volume: 20
Issue: 11
ISSN: 1530-6984
Publisher: American Chemical Society  
Date Published: 2020-11-11
Start Page: 7819
End Page: 7827
Language: English
ACCESSION: WOS:000592495700003
DOI: 10.1021/acs.nanolett.0c01858
PROVIDER: wos
PUBMED: 33119310
Notes: Article -- Source: Wos
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MSK Authors
  1. Minkui Luo
    63 Luo
  2. Daniel Alan Heller
    73 Heller
  3. Prakrit Vaibhav Jena
    24 Jena
  4. Hanan Baker
    6 Baker
  5. Justin M Cheung
    3 Cheung
  6. Zvi Aharon Yaari
    3 Yaari