A Simple Colorimetric Assay of Bleomycin‐Mediated DNA Cleavage Utilizing Double‐Stranded DNA‐Modified Gold Nanoparticles. (25th October 2022)

• Record Type: Journal Article
• Authors: Akiyama, Yoshitsugu; Kimura, Kazunori; Komatsu, Syuuhei; Takarada, Tohru; Maeda, Mizuo; Kikuchi, Akihiko
• Is Part Of: Chembiochem. Volume 24:Number 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-25
• Subjects: bleomycin -- colorimetric assay -- DNA-modified gold nanoparticles -- DNA damaging agents -- non-crosslinking aggregation; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200451
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: A colorimetric assay of DNA cleavage by bleomycin (BLM) derivatives was developed utilizing high colloidal stability on double‐stranded (ds) DNA‐modified gold nanoparticles (dsDNA‐AuNPs) possessing a cleavage site. The assay was performed using dsDNA‐AuNPs treated with inactive BLM or activated BLM (Fe(II)⋅BLM). A 10‐min exposure in dsDNA‐AuNPs with inactive BLM treatment resulted in a rapid color change from red to purple because of salt‐induced non‐crosslinking aggregation of dsDNA‐AuNPs. In contrast, the addition of active Fe(II)⋅BLM retained the red color, probably because of the formation of protruding structures at the outermost phase of dsDNA‐AuNPs caused by BLM‐mediated DNA cleavage. Furthermore, the results of our model experiments indicate that oxidative base release and DNA‐cleavage pathways could be visually distinguished with color change. The present methodology was also applicable to model screening assays using several drugs with different mechanisms related to antitumor activity. These results strongly suggest that this assay with a rapid color change could lead to simple and efficient screening of potent antitumor agents. Abstract : The colorimetric detection of bleomycin (BLM)‐mediated DNA cleavage with sequence selectivity is successfully demonstrated using dsDNA‐AuNPs with high colloidal stability. Notably, the cleavage pathways between oxidative base release and DNA cleavage can be identified according to a change in color using a colloidal stability test applied to dsDNA‐AuNPs with a blunt end and dangling end.