Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 135, Issue 39, Pages 14726-14730Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja4056068
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Funding
- NIH [R01 EB005011 R01 HL116307, 3R01EB005011-06S1]
- Netherlands Organization for Scientific Research (NWO) Rubicon fellowship
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The cysteine cathepsins are a family of proteases that play important roles in both normal cellular physiology and many human diseases. In cancer, the activity of many of the cysteine cathepsins is upregulated and can be exploited for tumor imaging. Here we present the design and synthesis of a new class of quenched fluorescent activity-based probes (qABPs) containing a phenoxymethyl ketone (PMK) electrophile. These reagents show enhanced in vivo properties and broad reactivity resulting in dramatically improved labeling and tumor imaging properties compared to those of previously reported ABPs.
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