TY - JOUR
T1 - Synthesis and evaluation of new NIR-fluorescent probes for cathepsin B
T2 - ICT versus FRET as a turn-ON mode-of-action
AU - Kisin-Finfer, Einat
AU - Ferber, Shiran
AU - Blau, Rachel
AU - Satchi-Fainaro, Ronit
AU - Shabat, Doron
N1 - Funding Information:
D.S. and R.S.-F. thanks the Israel Science Foundation (ISF), the Binational Science Foundation (BSF) and the German Israeli Foundation (GIF) for financial support. This work was partially supported by grants from the Israeli National Nanotechnology Initiative (INNI), Focal Technology Area (FTA) program: Nanomedicine for Personalized Theranostics, and by The Leona M. and Harry B. Helmsley Nanotechnology Research Fund.
PY - 2014/6/1
Y1 - 2014/6/1
N2 - Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix. Consequently, this protease has been attracting significant attention in cancer research, and many imaging probes targeting its activity have been developed. Here, we describe the design, synthesis and evaluation of two novel near infrared (NIR) fluorescent probes for detection of cathepsin B activity with different turn-ON mechanisms. One probe is based on an ICT activation mechanism of a donor-two-acceptor π-electron dye system, while the other is based on the FRET mechanism obtained by a fluorescent dye and a quencher. The two probes exhibit significant fluorescent turn-ON response upon cleavage by cathepsin B. The NIR fluorescence of the ICT probe in its OFF state was significantly lower than that of the FRET-based probe. This effect results in a higher signal-to-noise ratio and consequently increased sensitivity and better image contrast.
AB - Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix. Consequently, this protease has been attracting significant attention in cancer research, and many imaging probes targeting its activity have been developed. Here, we describe the design, synthesis and evaluation of two novel near infrared (NIR) fluorescent probes for detection of cathepsin B activity with different turn-ON mechanisms. One probe is based on an ICT activation mechanism of a donor-two-acceptor π-electron dye system, while the other is based on the FRET mechanism obtained by a fluorescent dye and a quencher. The two probes exhibit significant fluorescent turn-ON response upon cleavage by cathepsin B. The NIR fluorescence of the ICT probe in its OFF state was significantly lower than that of the FRET-based probe. This effect results in a higher signal-to-noise ratio and consequently increased sensitivity and better image contrast.
KW - Cathepsin B
KW - Cyanine dyes
KW - Fluorescent probes
KW - Near infrared fluorescence
UR - http://www.scopus.com/inward/record.url?scp=84899972504&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2014.04.022
DO - 10.1016/j.bmcl.2014.04.022
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AN - SCOPUS:84899972504
SN - 0960-894X
VL - 24
SP - 2453
EP - 2458
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 11
ER -
