Issue 17, 2023

Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis

Abstract

The M3 metalloproteases, neurolysin and THOP1, are neuropeptidases that are expressed in various tissues and metabolize neuropeptides, such as neurotensin. The biological roles of these enzymes are not well characterized, partially because the chemical tools to analyse their activities are not well developed. Here, we developed a fluorogenic substrate probe for neurolysin and thimet oligopeptidase 1 (THOP1), which enabled the analysis of enzymatic activity changes in tissue and plasma samples. In particular, the probe was useful for studying enzyme activities in a single-molecule enzyme assay platform, which can detect enzyme activity with high sensitivity. We detected the activity of neurolysin in plasma samples and revealed higher enzyme activity in the blood samples of patients with colorectal tumor. The result indicated that single-molecule neurolysin activity is a promising candidate for a blood biomarker for colorectal cancer diagnosis.

Graphical abstract: Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Dec 2022
Accepted
29 Mar 2023
First published
11 Apr 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 4495-4499

Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis

N. Nagano, Y. Ichihashi, T. Komatsu, H. Matsuzaki, K. Hata, T. Watanabe, Y. Misawa, M. Suzuki, S. Sakamoto, Y. Kagami, A. Kashiro, K. Takeuchi, Y. Kanemitsu, H. Ochiai, R. Watanabe, K. Honda and Y. Urano, Chem. Sci., 2023, 14, 4495 DOI: 10.1039/D2SC07029D

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