Issue 7, 2022

Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity

Abstract

Monitoring the activities of proteases in vivo is an important requirement in biological and medical research. Near-infrared (NIR) fluorescent probes are particularly useful for in vivo fluorescence imaging, due to the high penetration of NIR and the low autofluorescence in tissue for this wavelength region, but most current NIR fluorescent probes for proteases are targeted to endopeptidase. Here, we describe a new molecular design for NIR fluorescent probes that target exopeptidase by utilizing the >110 nm blueshift of unsymmetrical Si–rhodamines upon amidation of the N atom of their xanthene moiety. Based on this molecular design, we developed Leu-SiR640 as a probe for leucine amino peptidase (LAP). Leu-SiR640 shows a one order of magnitude larger fluorescence increment (669-fold) upon reaction with LAP than existing NIR fluorescent probes. We similarly designed and synthesized EP-SiR640, a NIR fluorescent probe that targets dipeptidyl peptidase 4 (DPP-4). We show that this probe can monitor DPP-4 activity not only in living cells but also in mouse organs and tumors. This probe could also detect esophageal cancer in human clinical specimens, based on the overexpression of DPP-4 activity.

Graphical abstract: Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity

Supplementary files

Article information

Article type
Paper
Submitted
24 Dec. 2021
Accepted
02 Marts 2022
First published
24 Marts 2022
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2022,3, 859-867

Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity

Y. Hoshino, K. Hanaoka, K. Sakamoto, M. Yasunaga, T. Kojima, D. Kotani, A. Nomoto, E. Sasaki, T. Komatsu, T. Ueno, H. Takamaru, Y. Saito, Y. Seto and Y. Urano, RSC Chem. Biol., 2022, 3, 859 DOI: 10.1039/D1CB00253H

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